Medicine › Otorhinolaryngology

Head and Neck Cancer Studies

Works Count: 95277

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Description

This cluster of papers focuses on the epidemiology, treatment, and prognosis of head and neck cancer, with a particular emphasis on human papillomavirus (HPV)-related oropharyngeal cancer. It covers topics such as the impact of HPV infection, the role of radiotherapy and chemotherapy, survival outcomes, and the molecular landscape of head and neck squamous cell carcinomas.

Keywords

Human Papillomavirus; Oropharyngeal Cancer; Radiotherapy; Chemotherapy; Squamous Cell Carcinoma; Survival; Nasopharyngeal Carcinoma; HPV Infection; Cetuximab; Prognosis

Prevention of Second Primary Tumors with Isotretinoin in Squamous-Cell Carcinoma of the Head and Neck

1990-09-20

Waun Ki Hong , S. M. Lippman , Loretta M. Itri +7 more

Patients with head-and-neck cancers who are free of disease after local therapy remain at high risk for both recurrent and second primary tumors. Retinoids have proved efficacious in the treatment … Patients with head-and-neck cancers who are free of disease after local therapy remain at high risk for both recurrent and second primary tumors. Retinoids have proved efficacious in the treatment of premalignant oral lesions and are promising agents for the prevention of epithelial carcinogenesis.We prospectively studied 103 patients who were disease-free after primary treatment for squamous-cell cancers of the larynx, pharynx, or oral cavity. After completion of surgery or radiotherapy (or both), these patients were randomly assigned to receive either isotretinoin (13-cis-retinoic acid) (50 to 100 mg per square meter of body-surface area per day) or placebo, to be taken daily for 12 months.There were no significant differences between the two groups in the number of local, regional, or distant recurrences of the primary cancers. However, the isotretinoin group had significantly fewer second primary tumors. After a median follow-up of 32 months, only 2 patients (4 percent) in the isotretinoin group had second primary tumors, as compared with 12 (24 percent) in the placebo group (P = 0.005). Multiple second primary tumors occurred in four patients, all of whom were in the placebo group. Of the 14 second cancers, 13 (93 percent) occurred in the head and neck, esophagus, or lung.Daily treatment with high doses of isotretinoin is effective in preventing second primary tumors in patients who have been treated for squamous-cell carcinoma of the head and neck, although it does not prevent recurrences of the original tumor.

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Mucositis incidence, severity and associated outcomes in patients with head and neck cancer receiving radiotherapy with or without chemotherapy: a systematic literature review

2003-03-01

Andy Trotti , Lisa A. Bellm , Joel B. Epstein +6 more

Cisplatin, Fluorouracil, and Docetaxel in Unresectable Head and Neck Cancer

2007-10-24

Jan B. Vermorken , Éva Remenár , Carla van Herpen +7 more

Phase 2 studies suggest that the standard regimen of cisplatin and fluorouracil (PF) plus docetaxel (TPF) improves outcomes in squamous-cell carcinoma of the head and neck. We compared TPF with … Phase 2 studies suggest that the standard regimen of cisplatin and fluorouracil (PF) plus docetaxel (TPF) improves outcomes in squamous-cell carcinoma of the head and neck. We compared TPF with PF as induction chemotherapy in patients with locoregionally advanced, unresectable disease.We randomly assigned eligible patients between the ages of 18 and 70 years who had stage III or stage IV disease and no distant metastases to receive either TPF (docetaxel and cisplatin, day 1; fluorouracil by continuous infusion, days 1 to 5) or PF every 3 weeks for four cycles. Patients without progression of disease received radiotherapy within 4 to 7 weeks after completing chemotherapy. The primary end point was progression-free survival.A total of 358 patients underwent randomization, with 177 assigned to the TPF group and 181 to the PF group. At a median follow-up of 32.5 months, the median progression-free survival was 11.0 months in the TPF group and 8.2 months in the PF group (hazard ratio for disease progression or death in the TPF group, 0.72; P=0.007). Treatment with TPF resulted in a reduction in the risk of death of 27% (P=0.02), with a median overall survival of 18.8 months, as compared with 14.5 months in the PF group. There were more grade 3 or 4 events of leukopenia and neutropenia in the TPF group and more grade 3 or 4 events of thrombocytopenia, nausea, vomiting, stomatitis, and hearing loss in the PF group. The rates of death from toxic effects were 2.3% in the TPF group and 5.5% in the PF group.As compared with the standard regimen of cisplatin and fluorouracil, induction chemotherapy with the addition of docetaxel significantly improved progression-free and overall survival in patients with unresectable squamous-cell carcinoma of the head and neck. (ClinicalTrials.gov number, NCT00003888 [ClinicalTrials.gov].).

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The molecular biology of head and neck cancer

2010-12-16

C. René Leemans , Boudewijn J.M. Braakhuis , Ruud H. Brakenhoff

Levels of TGF-α and EGFR Protein in Head and Neck Squamous Cell Carcinoma and Patient Survival

1998-06-03

Jennifer R. Grandis , Mona F. Melhem , William E. Gooding +5 more

The most accurate predictor of disease recurrence in patients treated for head and neck squamous cell carcinoma is, at present, the extent of regional lymph node metastasis. Since elevated levels … The most accurate predictor of disease recurrence in patients treated for head and neck squamous cell carcinoma is, at present, the extent of regional lymph node metastasis. Since elevated levels of epidermal growth factor receptor (EGFR) and of its ligand, transforming growth factor-alpha (TGF-alpha), have been detected in primary tumors of patients with head and neck squamous cell carcinoma, we determined whether tumor levels of these proteins were of prognostic importance.Monoclonal antibodies specific for EGFR and TGF-alpha were used for immunohistochemical detection of each protein in tissue sections of primary tumors from 91 patients who were treated by surgical resection. Levels of immunoreactive EGFR and TGF-alpha were quantified by use of a computerized image analysis system and were normalized to appropriate standards. The logrank test and proportional hazards regression analysis were used to calculate the probability that EGFR and TGF-alpha levels were associated with disease-free survival (i.e., no recurrence of cancer) and cause-specific survival (i.e., patients do not die of their disease). All P values were two-sided.When tumor levels of EGFR or TGF-alpha were analyzed as continuous variables, disease-free survival and cause-specific survival were reduced among patients with higher levels of EGFR (both P = .0001) or TGF-alpha (both P = .0001). In a multivariate analysis, tumor site, tumor level of EGFR, and tumor level of TGF-alpha were statistically significant predictors of disease-free survival; in a similar analysis, regional lymph node stage and tumor levels of EGFR and of TGF-alpha were significant predictors of cause-specific survival.Quantitation of EGFR and TGF-alpha protein levels in primary head and neck squamous cell carcinomas may be useful in identifying subgroups of patients at high risk of tumor recurrence and in guiding therapy.

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Larynx Preservation in Pyriform Sinus Cancer: Preliminary Results of a European Organization for Research and Treatment of Cancer Phase III Trial

1996-07-03

J.-L. Lefebvre , Dominique Chevalier , B Luboïnski +3 more

Background : As a general rule, surgery whenever possible, followed by irradiation is considered to be the standard treatment for cancer of the hypopharynx, thus sacrificing natural speech. In most … Background : As a general rule, surgery whenever possible, followed by irradiation is considered to be the standard treatment for cancer of the hypopharynx, thus sacrificing natural speech. In most patients, surgery includes removal of the larynx. Purpose : A prospective, randomized phase III study was conducted by the European Organization for Research and Treatment of Cancer (EORTC) starting in 1990 to compare a larynx-preserving treatment (induction chemotherapy plus definitive, radiation therapy in patients who showed a complete response or surgery in those who did not respond) with conventional treatment (total laryngectomy with partial pharyngectomy, radical neck dissection, and postoperative irradiation) in previously untreated and operable patients with histologically proven squamous cell carcinomas of the pyriform sinus or aryepiglottic fold, but free of other cancers. Methods : Patients were randomly assigned to one of two treatment arms: 1) immediate surgery with postoperative radiotherapy (50–70 Gy) or 2) induction chemotherapy (cisplatin [100 mg/m 2 ] given as a bolus intravenous injection on day 1, followed by infusion of fluorouracil [1000 mg/m 2 per day] on days 1–5). An endoscopic evaluation was performed after each cycle of chemotherapy. After two cycles, only partial and complete responders received a third cycle. Patients with a complete response after two or three cycles of chemotherapy were treated thereafter by irradiation (70 Gy); nonresponding patients underwent conventional surgery with postoperative radiation (50–70 Gy). Salvage surgery was also performed when patients relapsed after chemotherapy and irradiation. The trial was designed to test the equivalence of the two treatment arms; i.e., the induction chemotherapy treatment would be judged equivalent to immediate surgery if the relative risk of death for induction chemotherapy compared with immediate surgery was significantly less than 1.43 using a one-sided hypothesis test at the.05 level of significance. Results : Two hundred two patients entered the trial and were randomly assigned; only 194 were eligible for treatment (94 in the immediate-surgery arm and 100 in the induction-chemotherapy arm). In the induction-chemotherapy arm, complete response was seen in 52 (54%) of 97 patients with local disease (primary tumor) and in 31 (51%) of 61 patients with regional disease (involvement of the neck). Treatment failures at local, regional, and second primary sites occurred at approximately the same frequencies in the immediate-surgery arm (12%, 19%, and 16%, respectively) and in the induction-chemotherapy arm (17%, 23%, and 13%, respectively). In contrast, there were fewer failures at distant sites in the induction-chemotherapy arm than in the immediate-surgery arm (25% versus 36%, respectively; P =.041). The median duration of survival was 25 months in the immediate-surgery arm and 44 months in the induction-chemotherapy arm and, since the observed hazard ratio was 0.86 (logrank test, P =.006), which was significantly less than 1.43, the two treatments were judged to be equivalent. The 3- and 5-year estimates of retaining a functional larynx in patients treated in the induction chemotherapy arm were 42% (95% confidence interval = 31%-53%) and 35% (95% confidence interval = 22%-48%), respectively. Conclusions and Implications : Larynx preservation without jeopardizing survival appears feasible in patients with cancer of the hypopharynx. On the basis of these observations, the EORTC has now accepted the use of induction chemotherapy followed by radiation as the new standard treatment in its future phase III larynx preservation trials. [J Natl Cancer Inst 1996; 88: 890–9]

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An Intergroup Phase III Comparison of Standard Radiation Therapy and Two Schedules of Concurrent Chemoradiotherapy in Patients With Unresectable Squamous Cell Head and Neck Cancer

2002-12-28

David J. Adelstein , Yi Li , George L. Adams +5 more

The Head and Neck Intergroup conducted a phase III randomized trial to test the benefit of adding chemotherapy to radiation in patients with unresectable squamous cell head and neck cancer.Eligible … The Head and Neck Intergroup conducted a phase III randomized trial to test the benefit of adding chemotherapy to radiation in patients with unresectable squamous cell head and neck cancer.Eligible patients were randomly assigned between arm A (the control), single daily fractionated radiation (70 Gy at 2 Gy/d); arm B, identical radiation therapy with concurrent bolus cisplatin, given on days 1, 22, and 43; and arm C, a split course of single daily fractionated radiation and three cycles of concurrent infusional fluorouracil and bolus cisplatin chemotherapy, 30 Gy given with the first cycle and 30 to 40 Gy given with the third cycle. Surgical resection was encouraged if possible after the second chemotherapy cycle on arm C and, if necessary, as salvage therapy on all three treatment arms. Survival data were compared between each experimental arm and the control arm using a one-sided log-rank test.Between 1992 and 1999, 295 patients were entered on this trial. This did not meet the accrual goal of 362 patients and resulted in premature study closure. Grade 3 or worse toxicity occurred in 52% of patients enrolled in arm A, compared with 89% enrolled in arm B (P <.0001) and 77% enrolled in arm C (P <.001). With a median follow-up of 41 months, the 3-year projected overall survival for patients enrolled in arm A is 23%, compared with 37% for arm B (P =.014) and 27% for arm C (P = not significant).The addition of concurrent high-dose, single-agent cisplatin to conventional single daily fractionated radiation significantly improves survival, although it also increases toxicity. The loss of efficacy resulting from split-course radiation was not offset by either multiagent chemotherapy or the possibility of midcourse surgery.

HPV-associated head and neck cancer: a virus-related cancer epidemic

2010-05-06

Shanthi Marur , Gypsyamber D’Souza , William H. Westra +1 more

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Head and Neck Cancer

2001-12-27

Arlene A. Forastiere , Wayne M. Koch , A. Trotti +1 more

Head and neck cancers include neoplasms of the oral cavity, pharynx, and larynx. The risk of these cancers is strongly associated with smoking and alcohol ingestion. There have been important … Head and neck cancers include neoplasms of the oral cavity, pharynx, and larynx. The risk of these cancers is strongly associated with smoking and alcohol ingestion. There have been important advances in understanding of the molecular pathogenesis and progression of head and neck cancer and also in approaches to therapy, which include innovations in surgery, radiation therapy, and cytotoxic-drug therapy.

Locoregional Recurrence After Sentinel Lymph Node Dissection With or Without Axillary Dissection in Patients With Sentinel Lymph Node Metastases

2010-08-25

Armando E. Giuliano , Linda McCall , Peter D. Beitsch +7 more

Sentinel lymph node dissection (SLND) has eliminated the need for axillary dissection (ALND) in patients whose sentinel node (SN) is tumor-free. However, completion ALND for patients with tumor-involved SNs remains … Sentinel lymph node dissection (SLND) has eliminated the need for axillary dissection (ALND) in patients whose sentinel node (SN) is tumor-free. However, completion ALND for patients with tumor-involved SNs remains the standard to achieve locoregional control. Few studies have examined the outcome of patients who do not undergo ALND for positive SNs. We now report local and regional recurrence information from the American College of Surgeons Oncology Group Z0011 trial.American College of Surgeons Oncology Group Z0011 was a prospective trial examining survival of patients with SN metastases detected by standard H and E, who were randomized to undergo ALND after SLND versus SLND alone without specific axillary treatment. Locoregional recurrence was evaluated.There were 446 patients randomized to SLND alone and 445 to SLND + ALND. Patients in the 2 groups were similar with respect to age, Bloom-Richardson score, estrogen receptor status, use of adjuvant systemic therapy, tumor type, T stage, and tumor size. Patients randomized to SLND + ALND had a median of 17 axillary nodes removed compared with a median of only 2 SN removed with SLND alone (P < 0.001). ALND also removed more positive lymph nodes (P < 0.001). At a median follow-up time of 6.3 years, there were no statistically significant differences in local recurrence (P = 0.11) or regional recurrence (P = 0.45) between the 2 groups.Despite the potential for residual axillary disease after SLND, SLND without ALND can offer excellent regional control and may be reasonable management for selected patients with early-stage breast cancer treated with breast-conserving therapy and adjuvant systemic therapy.

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Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): An update on 93 randomised trials and 17,346 patients

2009-05-15

Jean‐Pierre Pignon , Aurélie Le Maître , E. Maillard +1 more

Concurrent Chemotherapy and Radiotherapy for Organ Preservation in Advanced Laryngeal Cancer

2003-11-26

Arlene A. Forastiere , Helmuth Goepfert , Moshe Maor +7 more

Induction chemotherapy with cisplatin plus fluorouracil followed by radiotherapy is the standard alternative to total laryngectomy for patients with locally advanced laryngeal cancer. The value of adding chemotherapy to radiotherapy … Induction chemotherapy with cisplatin plus fluorouracil followed by radiotherapy is the standard alternative to total laryngectomy for patients with locally advanced laryngeal cancer. The value of adding chemotherapy to radiotherapy and the optimal timing of chemotherapy are unknown.

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Worldwide Trends in Incidence Rates for Oral Cavity and Oropharyngeal Cancers

2013-11-19

Anil K. Chaturvedi , William F. Anderson , Joannie Lortet‐Tieulent +6 more

Human papillomavirus (HPV) has been identified as the cause of the increasing oropharyngeal cancer (OPC) incidence in some countries. To investigate whether this represents a global phenomenon, we evaluated incidence … Human papillomavirus (HPV) has been identified as the cause of the increasing oropharyngeal cancer (OPC) incidence in some countries. To investigate whether this represents a global phenomenon, we evaluated incidence trends for OPCs and oral cavity cancers (OCCs) in 23 countries across four continents.We used data from the Cancer Incidence in Five Continents database Volumes VI to IX (years 1983 to 2002). Using age-period-cohort modeling, incidence trends for OPCs were compared with those of OCCs and lung cancers to delineate the potential role of HPV vis-à-vis smoking on incidence trends. Analyses were country specific and sex specific.OPC incidence significantly increased during 1983 to 2002 predominantly in economically developed countries. Among men, OPC incidence significantly increased in the United States, Australia, Canada, Japan, and Slovakia, despite nonsignificant or significantly decreasing incidence of OCCs. In contrast, among women, in all countries with increasing OPC incidence (Denmark, Estonia, France, the Netherlands, Poland, Slovakia, Switzerland, and United Kingdom), there was a concomitant increase in incidence of OCCs. Although increasing OPC incidence among men was accompanied by decreasing lung cancer incidence, increasing incidence among women was generally accompanied by increasing lung cancer incidence. The magnitude of increase in OPC incidence among men was significantly higher at younger ages (< 60 years) than older ages in the United States, Australia, Canada, Slovakia, Denmark, and United Kingdom.OPC incidence significantly increased during 1983 to 2002 predominantly in developed countries and at younger ages. These results underscore a potential role for HPV infection on increasing OPC incidence, particularly among men.

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Head and neck cancer

2008-05-01

Athanassios Argiris , Michalis V. Karamouzis , David Raben +1 more

Human Papillomavirus and Survival of Patients with Oropharyngeal Cancer

2010-06-08

K. Kian Ang , Jonathan Harris , Richard Wheeler +7 more

Oropharyngeal squamous-cell carcinomas caused by human papillomavirus (HPV) are associated with favorable survival, but the independent prognostic significance of tumor HPV status remains unknown.We performed a retrospective analysis of the … Oropharyngeal squamous-cell carcinomas caused by human papillomavirus (HPV) are associated with favorable survival, but the independent prognostic significance of tumor HPV status remains unknown.We performed a retrospective analysis of the association between tumor HPV status and survival among patients with stage III or IV oropharyngeal squamous-cell carcinoma who were enrolled in a randomized trial comparing accelerated-fractionation radiotherapy (with acceleration by means of concomitant boost radiotherapy) with standard-fractionation radiotherapy, each combined with cisplatin therapy, in patients with squamous-cell carcinoma of the head and neck. Proportional-hazards models were used to compare the risk of death among patients with HPV-positive cancer and those with HPV-negative cancer.The median follow-up period was 4.8 years. The 3-year rate of overall survival was similar in the group receiving accelerated-fractionation radiotherapy and the group receiving standard-fractionation radiotherapy (70.3% vs. 64.3%; P=0.18; hazard ratio for death with accelerated-fractionation radiotherapy, 0.90; 95% confidence interval [CI], 0.72 to 1.13), as were the rates of high-grade acute and late toxic events. A total of 63.8% of patients with oropharyngeal cancer (206 of 323) had HPV-positive tumors; these patients had better 3-year rates of overall survival (82.4%, vs. 57.1% among patients with HPV-negative tumors; P<0.001 by the log-rank test) and, after adjustment for age, race, tumor and nodal stage, tobacco exposure, and treatment assignment, had a 58% reduction in the risk of death (hazard ratio, 0.42; 95% CI, 0.27 to 0.66). The risk of death significantly increased with each additional pack-year of tobacco smoking. Using recursive-partitioning analysis, we classified our patients as having a low, intermediate, or high risk of death on the basis of four factors: HPV status, pack-years of tobacco smoking, tumor stage, and nodal stage.Tumor HPV status is a strong and independent prognostic factor for survival among patients with oropharyngeal cancer. (ClinicalTrials.gov number, NCT00047008.)

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Factors Associated With Severe Late Toxicity After Concurrent Chemoradiation for Locally Advanced Head and Neck Cancer: An RTOG Analysis

2008-06-17

Mitchell Machtay , Jennifer Moughan , A. Trotti +5 more

Purpose Concurrent chemoradiotherapy (CCRT) for squamous cell carcinoma of the head and neck (SCCHN) increases both local tumor control and toxicity. This study evaluates clinical factors that are associated with … Purpose Concurrent chemoradiotherapy (CCRT) for squamous cell carcinoma of the head and neck (SCCHN) increases both local tumor control and toxicity. This study evaluates clinical factors that are associated with and might predict severe late toxicity after CCRT. Methods Patients were analyzed from a subset of three previously reported Radiation Therapy Oncology Group (RTOG) trials of CCRT for locally advanced SCCHN (RTOG 91-11, 97-03, and 99-14). Severe late toxicity was defined in this secondary analysis as chronic grade 3 to 4 pharyngeal/laryngeal toxicity (RTOG/European Organisation for the Research and Treatment of Cancer late toxicity scoring system) and/or requirement for a feeding tube ≥ 2 years after registration and/or potential treatment-related death (eg, pneumonia) within 3 years. Case-control analysis was performed, with a multivariable logistic regression model that included pretreatment and treatment potential factors. Results A total of 230 patients were assessable for this analysis: 99 patients with severe late toxicities and 131 controls; thus, 43% of assessable patients had a severe late toxicity. On multivariable analysis, significant variables correlated with the development of severe late toxicity were older age (odds ratio 1.05 per year; P = .001); advanced T stage (odds ratio, 3.07; P = .0036); larynx/hypopharynx primary site (odds ratio, 4.17; P = .0041); and neck dissection after CRT (odds ratio, 2.39; P = .018). Conclusion Severe late toxicity after CCRT is common. Older age, advanced T-stage, and larynx/hypopharynx primary site were strong independent risk factors. Neck dissection after CCRT was associated with an increased risk of these complications.

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Platinum-Based Chemotherapy plus Cetuximab in Head and Neck Cancer

2008-09-10

Jan B. Vermorken , Ricard Mesı́a , Fernando Rivera +7 more

Cetuximab is effective in platinum-resistant recurrent or metastatic squamous-cell carcinoma of the head and neck. We investigated the efficacy of cetuximab plus platinum-based chemotherapy as first-line treatment in patients with … Cetuximab is effective in platinum-resistant recurrent or metastatic squamous-cell carcinoma of the head and neck. We investigated the efficacy of cetuximab plus platinum-based chemotherapy as first-line treatment in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck.We randomly assigned 220 of 442 eligible patients with untreated recurrent or metastatic squamous-cell carcinoma of the head and neck to receive cisplatin (at a dose of 100 mg per square meter of body-surface area on day 1) or carboplatin (at an area under the curve of 5 mg per milliliter per minute, as a 1-hour intravenous infusion on day 1) plus fluorouracil (at a dose of 1000 mg per square meter per day for 4 days) every 3 weeks for a maximum of 6 cycles and 222 patients to receive the same chemotherapy plus cetuximab (at a dose of 400 mg per square meter initially, as a 2-hour intravenous infusion, then 250 mg per square meter, as a 1-hour intravenous infusion per week) for a maximum of 6 cycles. Patients with stable disease who received chemotherapy plus cetuximab continued to receive cetuximab until disease progression or unacceptable toxic effects, whichever occurred first.Adding cetuximab to platinum-based chemotherapy with fluorouracil (platinum-fluorouracil) significantly prolonged the median overall survival from 7.4 months in the chemotherapy-alone group to 10.1 months in the group that received chemotherapy plus cetuximab (hazard ratio for death, 0.80; 95% confidence interval, 0.64 to 0.99; P=0.04). The addition of cetuximab prolonged the median progression-free survival time from 3.3 to 5.6 months (hazard ratio for progression, 0.54; P<0.001) and increased the response rate from 20% to 36% (P<0.001). The most common grade 3 or 4 adverse events in the chemotherapy-alone and cetuximab groups were anemia (19% and 13%, respectively), neutropenia (23% and 22%), and thrombocytopenia (11% in both groups). Sepsis occurred in 9 patients in the cetuximab group and in 1 patient in the chemotherapy-alone group (P=0.02). Of 219 patients receiving cetuximab, 9% had grade 3 skin reactions and 3% had grade 3 or 4 infusion-related reactions. There were no cetuximab-related deaths.As compared with platinum-based chemotherapy plus fluorouracil alone, cetuximab plus platinum-fluorouracil chemotherapy improved overall survival when given as first-line treatment in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck. (ClinicalTrials.gov number, NCT00122460.)

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Postoperative Irradiation with or without Concomitant Chemotherapy for Locally Advanced Head and Neck Cancer

2004-05-05

Jacques Bernier , C. Domenge , Mahmut Özsahin +7 more

We compared concomitant cisplatin and irradiation with radiotherapy alone as adjuvant treatment for stage III or IV head and neck cancer. We compared concomitant cisplatin and irradiation with radiotherapy alone as adjuvant treatment for stage III or IV head and neck cancer.

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Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: phase III randomized Intergroup study 0099.

1998-04-01

Muhyi Al‐Sarraf , Michael LeBlanc , Padmini Giri +7 more

PURPOSE The Southwest Oncology Group (SWOG) coordinated an Intergroup study with the participation of Radiation Therapy Oncology Group (RTOG), and Eastern Cooperative Oncology Group (ECOG). This randomized phase III trial … PURPOSE The Southwest Oncology Group (SWOG) coordinated an Intergroup study with the participation of Radiation Therapy Oncology Group (RTOG), and Eastern Cooperative Oncology Group (ECOG). This randomized phase III trial compared chemoradiotherapy versus radiotherapy alone in patients with nasopharyngeal cancers. MATERIALS AND METHODS Radiotherapy was administered in both arms: 1.8- to 2.0-Gy/d fractions Monday to Friday for 35 to 39 fractions for a total dose of 70 Gy. The investigational arm received chemotherapy with cisplatin 100 mg/m2 on days 1, 22, and 43 during radiotherapy; postradiotherapy, chemotherapy with cisplatin 80 mg/m2 on day 1 and fluorouracil 1,000 mg/m2/d on days 1 to 4 was administered every 4 weeks for three courses. Patients were stratified by tumor stage, nodal stage, performance status, and histology. RESULTS Of 193 patients registered, 147 (69 radiotherapy and 78 chemoradiotherapy) were eligible for primary analysis for survival and toxicity. The median progression-free survival (PFS) time was 15 months for eligible patients on the radiotherapy arm and was not reached for the chemo-radiotherapy group. The 3-year PFS rate was 24% versus 69%, respectively (P < .001). The median survival time was 34 months for the radiotherapy group and not reached for the chemo-radiotherapy group, and the 3-year survival rate was 47% versus 78%, respectively (P = .005). One hundred eighty-five patients were included in a secondary analysis for survival. The 3-year survival rate for patients randomized to radiotherapy was 46%, and for the chemoradiotherapy group was 76% (P < .001). CONCLUSION We conclude that chemoradiotherapy is superior to radiotherapy alone for patients with advanced nasopharyngeal cancers with respect to PFS and overall survival.

Improved Survival of Patients With Human Papillomavirus-Positive Head and Neck Squamous Cell Carcinoma in a Prospective Clinical Trial

2008-02-12

Carole Fakhry , William H. Westra , S. Li +5 more

The improved prognosis for patients with human papillomavirus (HPV)–positive head and neck squamous cell carcinoma (HNSCC) relative to HPV-negative HNSCC observed in retrospective analyses remains to be confirmed in a … The improved prognosis for patients with human papillomavirus (HPV)–positive head and neck squamous cell carcinoma (HNSCC) relative to HPV-negative HNSCC observed in retrospective analyses remains to be confirmed in a prospective clinical trial. We prospectively evaluated the association of tumor HPV status with therapeutic response and survival among 96 patients with stage III or IV HNSCC of the oropharynx or larynx who participated in an Eastern Cooperative Oncology Group (ECOG) phase II trial and who received two cycles of induction chemotherapy with intravenous paclitaxel and carboplatin followed by concomitant weekly intravenous paclitaxel and standard fractionation radiation therapy. The presence or absence of HPV oncogenic types in tumors was determined by multiplex polymerase chain reaction (PCR) and in situ hybridization. Two-year overall and progression-free survival for HPV-positive and HPV-negative patients were estimated by Kaplan–Meier analysis. The relative hazard of mortality and progression for HPV-positive vs HPV-negative patients after adjustment for age, ECOG performance status, stage, and other covariables was estimated by use of a multivariable Cox proportional hazards model. All statistical tests were two-sided. Genomic DNA of oncogenic HPV types 16, 33, or 35 was located within tumor cell nuclei of 40% (95% confidence interval [CI] = 30% to 50%) of patients with HNSCC of the oropharynx or larynx by in situ hybridization and PCR. Compared with patients with HPV-negative tumors, patients with HPV-positive tumors had higher response rates after induction chemotherapy (82% vs 55%, difference = 27%, 95% CI = 9.3% to 44.7%, P = .01) and after chemoradiation treatment (84% vs 57%, difference = 27%, 95% CI = 9.7% to 44.3%, P = .007). After a median follow-up of 39.1 months, patients with HPV-positive tumors had improved overall survival (2-year overall survival = 95% [95% CI = 87% to 100%] vs 62% [95% CI = 49% to 74%], difference = 33%, 95% CI = 18.6% to 47.4%, P = .005, log-rank test) and, after adjustment for age, tumor stage, and ECOG performance status, lower risks of progression (hazard ratio [HR] = 0.27, 95% CI = 0.10 to 0.75), and death from any cause (HR = 0.36, 95% CI = 0.15 to 0.85) than those with HPV-negative tumors. For patients with HNSCC of the oropharynx, tumor HPV status is strongly associated with therapeutic response and survival.

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Incidence Trends for Human Papillomavirus–Related and –Unrelated Oral Squamous Cell Carcinomas in the United States

2008-01-30

Anil K. Chaturvedi , Eric A. Engels , William F. Anderson +1 more

To investigate the impact of human papillomavirus (HPV) on the epidemiology of oral squamous cell carcinomas (OSCCs) in the United States, we assessed differences in patient characteristics, incidence, and survival … To investigate the impact of human papillomavirus (HPV) on the epidemiology of oral squamous cell carcinomas (OSCCs) in the United States, we assessed differences in patient characteristics, incidence, and survival between potentially HPV-related and HPV-unrelated OSCC sites.Data from nine Surveillance, Epidemiology, and End Results program registries (1973 to 2004) were used to classify OSCCs by anatomic site as potentially HPV-related (n = 17,625) or HPV-unrelated (n = 28,144). Joinpoint regression and age-period-cohort models were used to assess incidence trends. Life-table analyses were used to compare 2-year overall survival for HPV-related and HPV-unrelated OSCCs.HPV-related OSCCs were diagnosed at younger ages than HPV-unrelated OSCCs (mean ages at diagnosis, 61.0 and 63.8 years, respectively; P < .001). Incidence increased significantly for HPV-related OSCC from 1973 to 2004 (annual percentage change [APC] = 0.80; P < .001), particularly among white men and at younger ages. By contrast, incidence for HPV-unrelated OSCC was stable through 1982 (APC = 0.82; P = .186) and declined significantly during 1983 to 2004 (APC = -1.85; P < .001). When treated with radiation, improvements in 2-year survival across calendar periods were more pronounced for HPV-related OSCCs (absolute increase in survival from 1973 through 1982 to 1993 through 2004 for localized, regional, and distant stages = 9.9%, 23.1%, and 18.6%, respectively) than HPV-unrelated OSCCs (5.6%, 3.1%, and 9.9%, respectively). During 1993 to 2004, for all stages treated with radiation, patients with HPV-related OSCCs had significantly higher survival rates than those with HPV-unrelated OSCCs.The proportion of OSCCs that are potentially HPV-related increased in the United States from 1973 to 2004, perhaps as a result of changing sexual behaviors. Recent improvements in survival with radiotherapy may be due in part to a shift in the etiology of OSCCs.

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Distinct Risk Factor Profiles for Human Papillomavirus Type 16–Positive and Human Papillomavirus Type 16–Negative Head and Neck Cancers

2008-03-12

Maura L. Gillison , Gypsyamber D’Souza , William H. Westra +4 more

High-risk types of human papillomavirus (HPV), including HPV-16, cause a subgroup of head and neck squamous cell carcinomas (HNSCCs). We examined whether the risk factors for HPV-16-positive HNSCCs are similar … High-risk types of human papillomavirus (HPV), including HPV-16, cause a subgroup of head and neck squamous cell carcinomas (HNSCCs). We examined whether the risk factors for HPV-16-positive HNSCCs are similar to those for HPV-16-negative HNSCCs in a hospital-based case-control study.Case subjects (n = 240) diagnosed with HNSCC at the Johns Hopkins Hospital from 2000 through 2006 were stratified by tumor HPV-16 status as determined by in situ hybridization. Two control subjects (n = 322) without cancer were individually matched by age and sex to each HPV-16-positive and HPV-16-negative case subject. Data on risk behaviors were obtained by use of audio computer-assisted self-interview technology. Multivariable conditional logistic regression models were used to estimate the odds ratios (ORs) for HPV-16-positive HNSCC and HPV-16-negative HNSCC associated with risk factors. All statistical tests were two-sided.HPV-16 was detected in 92 of 240 case subjects. HPV-16-positive HNSCC was independently associated with several measures of sexual behavior and exposure to marijuana but not with cumulative measures of tobacco smoking, alcohol drinking, or poor oral hygiene. Associations increased in strength with increasing number of oral sex partners (P(trend) = .01) and with increasing intensity (joints per month, P(trend) = .007), duration (in years, P(trend) = .01), and cumulative joint-years (P(trend) = .003) of marijuana use. By contrast, HPV-16-negative HNSCC was associated with measures of tobacco smoking, alcohol drinking, and poor oral hygiene but not with any measure of sexual behavior or marijuana use. Associations increased in strength with increasing intensity (cigarettes per day), duration, and cumulative pack-years of tobacco smoking (for all, P(trend) < .001), increasing years of heavy alcohol drinking (> or = 15 years of 14 drinks per week; P(trend) = .03), and increasing number of lost teeth (P(trend) = .001). Compared with subjects who neither smoked tobacco nor drank alcohol, those with heavy use of tobacco (> or = 20 pack-years) and alcohol had an increased risk of HPV-16-negative HNSCC (OR = 4.8, 95% confidence interval [CI] = 1.8 to 12) but not of HPV-16-positive HNSCC (OR = 0.67, 95% CI = 0.29 to 1.9).HPV-16-positive HNSCCs and HPV-16-negative HNSCCs have different risk factor profiles, indicating that they should be considered to be distinct cancers.

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Parotid-sparing intensity modulated versus conventional radiotherapy in head and neck cancer (PARSPORT): a phase 3 multicentre randomised controlled trial

2011-01-14

Christopher M. Nutting , James P. Morden , Kevin J. Harrington +7 more

Xerostomia is the most common late side-effect of radiotherapy to the head and neck. Compared with conventional radiotherapy, intensity-modulated radiotherapy (IMRT) can reduce irradiation of the parotid glands. We assessed … Xerostomia is the most common late side-effect of radiotherapy to the head and neck. Compared with conventional radiotherapy, intensity-modulated radiotherapy (IMRT) can reduce irradiation of the parotid glands. We assessed the hypothesis that parotid-sparing IMRT reduces the incidence of severe xerostomia.We undertook a randomised controlled trial between Jan 21, 2003, and Dec 7, 2007, that compared conventional radiotherapy (control) with parotid-sparing IMRT. We randomly assigned patients with histologically confirmed pharyngeal squamous-cell carcinoma (T1-4, N0-3, M0) at six UK radiotherapy centres between the two radiotherapy techniques (1:1 ratio). A dose of 60 or 65 Gy was prescribed in 30 daily fractions given Monday to Friday. Treatment was not masked. Randomisation was by computer-generated permuted blocks and was stratified by centre and tumour site. Our primary endpoint was the proportion of patients with grade 2 or worse xerostomia at 12 months, as assessed by the Late Effects of Normal Tissue (LENT SOMA) scale. Analyses were done on an intention-to-treat basis, with all patients who had assessments included. Long-term follow-up of patients is ongoing. This study is registered with the International Standard Randomised Controlled Trial register, number ISRCTN48243537.47 patients were assigned to each treatment arm. Median follow-up was 44·0 months (IQR 30·0-59·7). Six patients from each group died before 12 months and seven patients from the conventional radiotherapy and two from the IMRT group were not assessed at 12 months. At 12 months xerostomia side-effects were reported in 73 of 82 alive patients; grade 2 or worse xerostomia at 12 months was significantly lower in the IMRT group than in the conventional radiotherapy group (25 [74%; 95% CI 56-87] of 34 patients given conventional radiotherapy vs 15 [38%; 23-55] of 39 given IMRT, p=0·0027). The only recorded acute adverse event of grade 2 or worse that differed significantly between the treatment groups was fatigue, which was more prevalent in the IMRT group (18 [41%; 99% CI 23-61] of 44 patients given conventional radiotherapy vs 35 [74%; 55-89] of 47 given IMRT, p=0·0015). At 24 months, grade 2 or worse xerostomia was significantly less common with IMRT than with conventional radiotherapy (20 [83%; 95% CI 63-95] of 24 patients given conventional radiotherapy vs nine [29%; 14-48] of 31 given IMRT; p<0·0001). At 12 and 24 months, significant benefits were seen in recovery of saliva secretion with IMRT compared with conventional radiotherapy, as were clinically significant improvements in dry-mouth-specific and global quality of life scores. At 24 months, no significant differences were seen between randomised groups in non-xerostomia late toxicities, locoregional control, or overall survival.Sparing the parotid glands with IMRT significantly reduces the incidence of xerostomia and leads to recovery of saliva secretion and improvements in associated quality of life, and thus strongly supports a role for IMRT in squamous-cell carcinoma of the head and neck.Cancer Research UK (CRUK/03/005).

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Long-Term Results of RTOG 91-11: A Comparison of Three Nonsurgical Treatment Strategies to Preserve the Larynx in Patients With Locally Advanced Larynx Cancer

2012-11-27

Arlene A. Forastiere , Qiang Zhang , Randal S. Weber +7 more

Purpose To report the long-term results of the Intergroup Radiation Therapy Oncology Group 91-11 study evaluating the contribution of chemotherapy added to radiation therapy (RT) for larynx preservation. Patients and … Purpose To report the long-term results of the Intergroup Radiation Therapy Oncology Group 91-11 study evaluating the contribution of chemotherapy added to radiation therapy (RT) for larynx preservation. Patients and Methods Patients with stage III or IV glottic or supraglottic squamous cell cancer were randomly assigned to induction cisplatin/fluorouracil (PF) followed by RT (control arm), concomitant cisplatin/RT, or RT alone. The composite end point of laryngectomy-free survival (LFS) was the primary end point. Results Five hundred twenty patients were analyzed. Median follow-up for surviving patients is 10.8 years. Both chemotherapy regimens significantly improved LFS compared with RT alone (induction chemotherapy v RT alone: hazard ratio [HR], 0.75; 95% CI, 0.59 to 0.95; P = .02; concomitant chemotherapy v RT alone: HR, 0.78; 95% CI, 0.78 to 0.98; P = .03). Overall survival did not differ significantly, although there was a possibility of worse outcome with concomitant relative to induction chemotherapy (HR, 1.25; 95% CI, 0.98 to 1.61; P = .08). Concomitant cisplatin/RT significantly improved the larynx preservation rate over induction PF followed by RT (HR, 0.58; 95% CI, 0.37 to 0.89; P = .0050) and over RT alone (P < .001), whereas induction PF followed by RT was not better than treatment with RT alone (HR, 1.26; 95% CI, 0.88 to 1.82; P = .35). No difference in late effects was detected, but deaths not attributed to larynx cancer or treatment were higher with concomitant chemotherapy (30.8% v 20.8% with induction chemotherapy and 16.9% with RT alone). Conclusion These 10-year results show that induction PF followed by RT and concomitant cisplatin/RT show similar efficacy for the composite end point of LFS. Locoregional control and larynx preservation were significantly improved with concomitant cisplatin/RT compared with the induction arm or RT alone. New strategies that improve organ preservation and function with less morbidity are needed.

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Case–Control Study of Human Papillomavirus and Oropharyngeal Cancer

2007-05-09

Gypsyamber D’Souza , Aimée R. Kreimer , Raphael P. Viscidi +5 more

Substantial molecular evidence suggests a role for human papillomavirus (HPV) in the pathogenesis of oropharyngeal squamous-cell carcinoma, but epidemiologic data have been inconsistent.We performed a hospital-based, case-control study of 100 … Substantial molecular evidence suggests a role for human papillomavirus (HPV) in the pathogenesis of oropharyngeal squamous-cell carcinoma, but epidemiologic data have been inconsistent.We performed a hospital-based, case-control study of 100 patients with newly diagnosed oropharyngeal cancer and 200 control patients without cancer to evaluate associations between HPV infection and oropharyngeal cancer. Multivariate logistic-regression models were used for case-control comparisons.A high lifetime number of vaginal-sex partners (26 or more) was associated with oropharyngeal cancer (odds ratio, 3.1; 95% confidence interval [CI], 1.5 to 6.5), as was a high lifetime number of oral-sex partners (6 or more) (odds ratio, 3.4; 95% CI, 1.3 to 8.8). The degree of association increased with the number of vaginal-sex and oral-sex partners (P values for trend, 0.002 and 0.009, respectively). Oropharyngeal cancer was significantly associated with oral HPV type 16 (HPV-16) infection (odds ratio, 14.6; 95% CI, 6.3 to 36.6), oral infection with any of 37 types of HPV (odds ratio, 12.3; 95% CI, 5.4 to 26.4), and seropositivity for the HPV-16 L1 capsid protein (odds ratio, 32.2; 95% CI, 14.6 to 71.3). HPV-16 DNA was detected in 72% (95% CI, 62 to 81) of 100 paraffin-embedded tumor specimens, and 64% of patients with cancer were seropositive for the HPV-16 oncoprotein E6, E7, or both. HPV-16 L1 seropositivity was highly associated with oropharyngeal cancer among subjects with a history of heavy tobacco and alcohol use (odds ratio, 19.4; 95% CI, 3.3 to 113.9) and among those without such a history (odds ratio, 33.6; 95% CI, 13.3 to 84.8). The association was similarly increased among subjects with oral HPV-16 infection, regardless of their tobacco and alcohol use. By contrast, tobacco and alcohol use increased the association with oropharyngeal cancer primarily among subjects without exposure to HPV-16.Oral HPV infection is strongly associated with oropharyngeal cancer among subjects with or without the established risk factors of tobacco and alcohol use.

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Cisplatin and Fluorouracil Alone or with Docetaxel in Head and Neck Cancer

2007-10-24

Marshall R. Posner , Diáne Hershock , C. Blajman +7 more

A randomized phase 3 trial of the treatment of squamous-cell carcinoma of the head and neck compared induction chemotherapy with docetaxel plus cisplatin and fluorouracil (TPF) with cisplatin and fluorouracil … A randomized phase 3 trial of the treatment of squamous-cell carcinoma of the head and neck compared induction chemotherapy with docetaxel plus cisplatin and fluorouracil (TPF) with cisplatin and fluorouracil (PF), followed by chemoradiotherapy.

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Defining risk levels in locally advanced head and neck cancers: A comparative analysis of concurrent postoperative radiation plus chemotherapy trials of the EORTC (#22931) and RTOG (# 9501)

2005-01-01

Jacques Bernier , Jay S. Cooper , Thomas F. Pajak +7 more

Background. In 2004, level I evidence was established for the postoperative adjuvant treatment of patients with selected high-risk locally advanced head and neck cancers, with the publication of the results … Background. In 2004, level I evidence was established for the postoperative adjuvant treatment of patients with selected high-risk locally advanced head and neck cancers, with the publication of the results of two trials conducted in Europe (European Organization Research and Treatment of Cancer; EORTC) and the United States (Radiation Therapy Oncology Group; RTOG). Adjuvant chemotherapy-enhanced radiation therapy (CERT) was shown to be more efficacious than postoperative radiotherapy for these tumors in terms of locoregional control and disease-free survival. However, additional studies were needed to identify precisely which patients were most suitable for such intense treatment. Methods. Both studies compared the addition of concomitant relatively high doses of cisplatin (on days 1, 22, and 43) to radiotherapy vs radiotherapy alone given after surgery in patients with high-risk cancers of the oral cavity, oropharynx, larynx, or hypopharynx. A comparative analysis of the selection criteria, clinical and pathologic risk factors, and treatment outcomes was carried out using data pooled from these two trials. Results. Extracapsular extension (ECE) and/or microscopically involved surgical margins were the only risk factors for which the impact of CERT was significant in both trials. There was also a trend in favor of CERT in the group of patients who had stage III–IV disease, perineural infiltration, vascular embolisms, and/or clinically enlarged level IV–V lymph nodes secondary to tumors arising in the oral cavity or oropharynx. Patients who had two or more histopathologically involved lymph nodes without ECE as their only risk factor did not seem to benefit from the addition of chemotherapy in this analysis. Conclusions. Subject to the usual caveats of retrospective subgroup analysis, our data suggest that in locally advanced head and neck cancer, microscopically involved resection margins and extracapsular spread of tumor from neck nodes are the most significant prognostic factors for poor outcome. The addition of concomitant cisplatin to postoperative radiotherapy improves outcome in patients with one or both of these risk factors who are medically fit to receive chemotherapy. © 2005 Wiley Periodicals, Inc. Head Neck 27: XXX–XXX, 2005

Human Papillomavirus and Rising Oropharyngeal Cancer Incidence in the United States

2011-10-04

Anil K. Chaturvedi , Eric A. Engels , Ruth M. Pfeiffer +7 more

Recent increases in incidence and survival of oropharyngeal cancers in the United States have been attributed to human papillomavirus (HPV) infection, but empirical evidence is lacking. Recent increases in incidence and survival of oropharyngeal cancers in the United States have been attributed to human papillomavirus (HPV) infection, but empirical evidence is lacking.

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Postoperative Concurrent Radiotherapy and Chemotherapy for High-Risk Squamous-Cell Carcinoma of the Head and Neck

2004-05-05

Jay S. Cooper , Thomas F. Pajak , Arlene A. Forastiere +7 more

Despite the use of resection and postoperative radiotherapy, high-risk squamous-cell carcinoma of the head and neck frequently recurs in the original tumor bed. We tested the hypothesis that concurrent postoperative … Despite the use of resection and postoperative radiotherapy, high-risk squamous-cell carcinoma of the head and neck frequently recurs in the original tumor bed. We tested the hypothesis that concurrent postoperative administration of cisplatin and radiotherapy would improve the rate of local and regional control.Between September 9, 1995, and April 28, 2000, 459 patients were enrolled. After undergoing total resection of all visible and palpable disease, 231 patients were randomly assigned to receive radiotherapy alone (60 to 66 Gy in 30 to 33 fractions over a period of 6 to 6.6 weeks) and 228 patients to receive the identical treatment plus concurrent cisplatin (100 mg per square meter of body-surface area intravenously on days 1, 22, and 43).After a median follow-up of 45.9 months, the rate of local and regional control was significantly higher in the combined-therapy group than in the group given radiotherapy alone (hazard ratio for local or regional recurrence, 0.61; 95 percent confidence interval, 0.41 to 0.91; P=0.01). The estimated two-year rate of local and regional control was 82 percent in the combined-therapy group, as compared with 72 percent in the radiotherapy group. Disease-free survival was significantly longer in the combined-therapy group than in the radiotherapy group (hazard ratio for disease or death, 0.78; 95 percent confidence interval, 0.61 to 0.99; P=0.04), but overall survival was not (hazard ratio for death, 0.84; 95 percent confidence interval, 0.65 to 1.09; P=0.19). The incidence of acute adverse effects of grade 3 or greater was 34 percent in the radiotherapy group and 77 percent in the combined-therapy group (P<0.001). Four patients who received combined therapy died as a direct result of the treatment.Among high-risk patients with resected head and neck cancer, concurrent postoperative chemotherapy and radiotherapy significantly improve the rates of local and regional control and disease-free survival. However, the combined treatment is associated with a substantial increase in adverse effects.

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Genetic progression model for head and neck cancer: implications for field cancerization.

1996-06-01

Joseph A. Califano , Peter van der Riet , William H. Westra +7 more

A genetic progression model of head and neck squamous cell carcinoma has not yet been elucidated, and the genetic basis for "field cancerization" of the aerodigestive tract has also remained … A genetic progression model of head and neck squamous cell carcinoma has not yet been elucidated, and the genetic basis for "field cancerization" of the aerodigestive tract has also remained obscure. Eighty-seven lesions of the head and neck, including preinvasive lesions and benign lesions associated with carcinogen exposure, were tested using microsatellite analysis for allelic loss at 10 major chromosomal loci which have been defined previously. The spectrum of chromosomal loss progressively increased at each histopathological step from benign hyperplasia to dysplasia to carcinoma in situ to invasive cancer. Adjacent areas of tissue with different histopathological appearance shared common genetic changes, but the more histopathologically advanced areas exhibited additional genetic alterations. Abnormal mucosal cells surrounding preinvasive and microinvasive lesions shared common genetic alterations with those lesions and thus appear to arise from a single progenitor clone. Based on these findings, the local clinical phenomenon of field cancerization seems to involve the expansion and migration of clonally related preneoplastic cells.

Interaction between Tobacco and Alcohol Use and the Risk of Head and Neck Cancer: Pooled Analysis in the International Head and Neck Cancer Epidemiology Consortium

2009-02-01

Mia Hashibe , Paul Brennan , Shu‐Chun Chuang +7 more

Abstract Background: The magnitude of risk conferred by the interaction between tobacco and alcohol use on the risk of head and neck cancers is not clear because studies have used … Abstract Background: The magnitude of risk conferred by the interaction between tobacco and alcohol use on the risk of head and neck cancers is not clear because studies have used various methods to quantify the excess head and neck cancer burden. Methods: We analyzed individual-level pooled data from 17 European and American case-control studies (11,221 cases and 16,168 controls) participating in the International Head and Neck Cancer Epidemiology consortium. We estimated the multiplicative interaction parameter (ψ) and population attributable risks (PAR). Results: A greater than multiplicative joint effect between ever tobacco and alcohol use was observed for head and neck cancer risk (ψ = 2.15; 95% confidence interval, 1.53-3.04). The PAR for tobacco or alcohol was 72% (95% confidence interval, 61-79%) for head and neck cancer, of which 4% was due to alcohol alone, 33% was due to tobacco alone, and 35% was due to tobacco and alcohol combined. The total PAR differed by subsite (64% for oral cavity cancer, 72% for pharyngeal cancer, 89% for laryngeal cancer), by sex (74% for men, 57% for women), by age (33% for cases &lt;45 years, 73% for cases &gt;60 years), and by region (84% in Europe, 51% in North America, 83% in Latin America). Conclusions: Our results confirm that the joint effect between tobacco and alcohol use is greater than multiplicative on head and neck cancer risk. However, a substantial proportion of head and neck cancers cannot be attributed to tobacco or alcohol use, particularly for oral cavity cancer and for head and neck cancer among women and among young-onset cases. (Cancer Epidemiol Biomarkers Prev 2009;18(2):541–50)

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Evidence for a Causal Association Between Human Papillomavirus and a Subset of Head and Neck Cancers

2000-05-03

Maura L. Gillison

High-risk human papillomaviruses (HPVs) are etiologic agents for anogenital tract cancers and have been detected in head and neck squamous cell carcinomas (HNSCCs). We investigated, retrospectively, an etiologic role for … High-risk human papillomaviruses (HPVs) are etiologic agents for anogenital tract cancers and have been detected in head and neck squamous cell carcinomas (HNSCCs). We investigated, retrospectively, an etiologic role for HPVs in a large series of patients with HNSCC.Tumor tissues from 253 patients with newly diagnosed or recurrent HNSCC were tested for the presence of HPV genome by use of polymerase chain reaction (PCR)-based assays, Southern blot hybridization, and in situ hybridization. The viral E6 coding region was sequenced to confirm the presence of tumor-specific viral isolates. Exons 5-9 of the TP53 gene were sequenced from 166 specimens. The hazard of death from HNSCC in patients with and without HPV-positive tumors was determined by proportional hazards regression analysis.HPV was detected in 62 (25%) of 253 cases (95% confidence interval [CI] = 19%-30%). High-risk, tumorigenic type HPV16 was identified in 90% of the HPV-positive tumors. HPV16 was localized specifically by in situ hybridization within the nuclei of cancer cells in preinvasive, invasive, and lymph node disease. Southern blot hybridization patterns were consistent with viral integration. Poor tumor grade (odds ratio [OR] = 2.4; 95% CI = 1.2- 4.9) and oropharyngeal site (OR = 6.2; 95% CI = 3.1-12.1) independently increased the probability of HPV presence. As compared with HPV-negative oropharyngeal cancers, HPV-positive oropharyngeal cancers were less likely to occur among moderate to heavy drinkers (OR = 0.17; 95% CI = 0.05-0.61) and smokers (OR = 0.16; 95% CI = 0.02-1.4), had a characteristic basaloid morphology (OR = 18.7; 95% CI = 2.1-167), were less likely to have TP53 mutations (OR = 0.06; 95% CI = 0.01-0. 36), and had improved disease-specific survival (hazard ratio [HR] = 0.26; 95% CI = 0.07-0.98). After adjustment for the presence of lymph node disease (HR = 2.3; 95% CI = 1.4- 3.8), heavy alcohol consumption (HR = 2.6; 95% CI = 1.4-4.7), and age greater than 60 years old (HR = 1.4; 95% CI = 0.8-2.3), all patients with HPV-positive tumors had a 59% reduction in risk of death from cancer when compared with HPV-negative HNSCC patients (HR = 0.41; 95% CI = 0.20-0.88).These data extend recent molecular and epidemiologic studies and strongly suggest that HPV-positive oropharyngeal cancers comprise a distinct molecular, clinical, and pathologic disease entity that is likely causally associated with HPV infection and that has a markedly improved prognosis.

Impact of epidermal growth factor receptor expression on survival and pattern of relapse in patients with advanced head and neck carcinoma.

2002-12-15

K. Kian Ang , Brian Berkey , Xiaoyu Tu +5 more

A correlative study was performed to address the impact of epidermal growth factor receptor (EGFR) overexpression on survival and pattern of failure in patients with advanced head and neck squamous … A correlative study was performed to address the impact of epidermal growth factor receptor (EGFR) overexpression on survival and pattern of failure in patients with advanced head and neck squamous cell carcinomas (HNSCCs) enrolled in a Phase III trial and randomized to receive conventional radiotherapy. The study population comprised 155 of 268 (58%) randomized patients with sufficient pretreatment biopsy specimens for immunohistochemical assay. The specimens were dewaxed and incubated after standard preparation with mouse monoclonal antibodies recognizing the extracellular domain of the EGFR molecule. The catalyzed product was visualized with 3,3'-diaminobenzidine Chromogen Kit and lightly counterstained with Mayer's hematoxylin. Quantitative EGFR immunohistochemistry (IHC) was done with SAMBA 4000 Cell Image Analysis System, without knowledge of the clinical outcome, to yield mean absorbance (MOD), staining index (SI), and quick score (QS). These EGFR IHC parameters were correlated with the T stage, N stage, combined stage grouping, and recursive partitioning analysis classes. Subsequently, the EGFR parameters were correlated with the outcome end points, i.e., overall survival (OS), disease-free survival (DFS), local-regional (LR) relapse, and distant metastasis rates. We found that HNSCCs exhibited a wide variation in EGFR expression (MOD, 0.2-66.0; SI, 0.3-97.0; QS, 0.01-69.9) with a relatively strong but nonlinear correlation between MOD and SI (r = 0.79). There was no correlation between EGFR expression and T stage, N stage, stage grouping, and recursive partitioning analysis classes (r = -0.07 to 0.17). The OS and DFS rates of patients with high EGFR-expressing HNSCCs (>median MOD) were highly significantly lower (P = 0.0006 and P = 0.0016, respectively) and the LR relapse rate was highly significantly higher (P = 0.0031) compared with those of patients with low EGFR-expressing HNSCCs. However, there was no difference in the distant metastasis rate between the two groups (P = 0.96). Significant correlations, although somewhat less robust than MOD, were also observed between SI and QS and the OS, DFS, and LR relapse rates. Multivariate analysis showed that EGFR expression was an independent determinant of survival and a robust independent predictor of LR relapse. In summary, this correlative study in a large series of patients revealed that EGFR expression, which varied considerably among HNSCCs, was a strong independent prognostic indicator for OS and DFS and a robust predictor for LR relapse but not for distant metastasis. The data suggest that EGFR IHC should be considered for selecting patients for more aggressive combined therapies or enrollment into trials targeting EGFR signaling pathways.

A radiation therapy oncology group (RTOG) phase III randomized study to compare hyperfractionation and two variants of accelerated fractionation to standard fractionation radiotherapy for head and neck squamous cell carcinomas: first report of RTOG 9003

2000-08-01

Karen K. Fu , Thomas F. Pajak , Andy Trotti +7 more

Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer: 5-year survival data from a phase 3 randomised trial, and relation between cetuximab-induced rash and survival

2009-11-12

James A. Bonner , Paul M. Harari , J. Giralt +7 more

Chemotherapy added to locoregional treatment for head and neck squamous-cell carcinoma: three meta-analyses of updated individual data

2000-03-01

Jean‐Pierre Pignon , Jean Bourhis , C. Domenge +1 more

Radiotherapy plus Cetuximab for Squamous-Cell Carcinoma of the Head and Neck

2006-02-08

James A. Bonner , Paul M. Harari , J. Giralt +7 more

We conducted a multinational, randomized study to compare radiotherapy alone with radiotherapy plus cetuximab, a monoclonal antibody against the epidermal growth factor receptor, in the treatment of locoregionally advanced squamous-cell … We conducted a multinational, randomized study to compare radiotherapy alone with radiotherapy plus cetuximab, a monoclonal antibody against the epidermal growth factor receptor, in the treatment of locoregionally advanced squamous-cell carcinoma of the head and neck.

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Hyperfractionated Irradiation with or without Concurrent Chemotherapy for Locally Advanced Head and Neck Cancer

1998-06-18

David M. Brizel , MARY ALBERS , Samuel R. Fisher +6 more

Radiotherapy is often the primary treatment for advanced head and neck cancer, but the rates of locoregional recurrence are high and survival is poor. We investigated whether hyperfractionated irradiation plus … Radiotherapy is often the primary treatment for advanced head and neck cancer, but the rates of locoregional recurrence are high and survival is poor. We investigated whether hyperfractionated irradiation plus concurrent chemotherapy (combined treatment) is superior to hyperfractionated irradiation alone.

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Head and Neck Cancer

1993-01-21

Everett E. Vokes , Ralph R. Weichselbaum , Scott M. Lippman +1 more

Head and neck cancer was last reviewed in the Journal in 19831. At that time, there was promising new information on a possible role for chemotherapy1,2. During the past decade, … Head and neck cancer was last reviewed in the Journal in 19831. At that time, there was promising new information on a possible role for chemotherapy1,2. During the past decade, chemotherapy has undergone further investigation and important clinical advances have been made in chemoprevention, organ preservation, and the simultaneous use of chemotherapy and radiation. In this review, we shall discuss the diagnosis of and standard therapy for head and neck cancer, as well as the status of recent basic and clinical investigations.EpidemiologyHead and neck cancer, as defined here, includes the common squamous-cell carcinomas of the . . .

Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck

2016-10-09

Robert L. Ferris , George R. Blumenschein , Jérôme Fayette +7 more

Patients with recurrent or metastatic squamous-cell carcinoma of the head and neck after platinum chemotherapy have a very poor prognosis and limited therapeutic options. Nivolumab, an anti-programmed death 1 (PD-1) … Patients with recurrent or metastatic squamous-cell carcinoma of the head and neck after platinum chemotherapy have a very poor prognosis and limited therapeutic options. Nivolumab, an anti-programmed death 1 (PD-1) monoclonal antibody, was assessed as treatment for this condition.In this randomized, open-label, phase 3 trial, we assigned, in a 2:1 ratio, 361 patients with recurrent squamous-cell carcinoma of the head and neck whose disease had progressed within 6 months after platinum-based chemotherapy to receive nivolumab (at a dose of 3 mg per kilogram of body weight) every 2 weeks or standard, single-agent systemic therapy (methotrexate, docetaxel, or cetuximab). The primary end point was overall survival. Additional end points included progression-free survival, rate of objective response, safety, and patient-reported quality of life.The median overall survival was 7.5 months (95% confidence interval [CI], 5.5 to 9.1) in the nivolumab group versus 5.1 months (95% CI, 4.0 to 6.0) in the group that received standard therapy. Overall survival was significantly longer with nivolumab than with standard therapy (hazard ratio for death, 0.70; 97.73% CI, 0.51 to 0.96; P=0.01), and the estimates of the 1-year survival rate were approximately 19 percentage points higher with nivolumab than with standard therapy (36.0% vs. 16.6%). The median progression-free survival was 2.0 months (95% CI, 1.9 to 2.1) with nivolumab versus 2.3 months (95% CI, 1.9 to 3.1) with standard therapy (hazard ratio for disease progression or death, 0.89; 95% CI, 0.70 to 1.13; P=0.32). The rate of progression-free survival at 6 months was 19.7% with nivolumab versus 9.9% with standard therapy. The response rate was 13.3% in the nivolumab group versus 5.8% in the standard-therapy group. Treatment-related adverse events of grade 3 or 4 occurred in 13.1% of the patients in the nivolumab group versus 35.1% of those in the standard-therapy group. Physical, role, and social functioning was stable in the nivolumab group, whereas it was meaningfully worse in the standard-therapy group.Among patients with platinum-refractory, recurrent squamous-cell carcinoma of the head and neck, treatment with nivolumab resulted in longer overall survival than treatment with standard, single-agent therapy. (Funded by Bristol-Myers Squibb; CheckMate 141 ClinicalTrials.gov number, NCT02105636 .).

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Induction Chemotherapy plus Radiation Compared with Surgery plus Radiation in Patients with Advanced Laryngeal Cancer

1991-06-13

Gregory T. Wolf , Susan G. Fisher , Waun Ki Hong +6 more

We performed a prospective, randomized study in patients with previously untreated advanced (Stage III or IV) laryngeal squamous carcinoma to compare the results of induction chemotherapy followed by definitive radiation … We performed a prospective, randomized study in patients with previously untreated advanced (Stage III or IV) laryngeal squamous carcinoma to compare the results of induction chemotherapy followed by definitive radiation therapy with those of conventional laryngectomy and postoperative radiation.

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The molecular landscape of head and neck cancer

2018-03-02

C. René Leemans , Peter J.F. Snijders , Ruud H. Brakenhoff

Radiotherapy plus cetuximab or cisplatin in human papillomavirus-positive oropharyngeal cancer (NRG Oncology RTOG 1016): a randomised, multicentre, non-inferiority trial

2018-11-15

Maura L. Gillison , Andy Trotti , Jonathan Harris +7 more

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WHO classification of head and neck tumours

2017-01-01

Adel K. El‐Naggar , John Chan , Jennifer R. Grandis +2 more

Head and Neck Cancer

2020-01-01

Laura Q.M. Chow

Most head and neck cancers (73% in the United States) are now related to human papillomavirus infection rather than tobacco and alcohol. Primary cancers are largely squamous-cell cancers, but combined … Most head and neck cancers (73% in the United States) are now related to human papillomavirus infection rather than tobacco and alcohol. Primary cancers are largely squamous-cell cancers, but combined treatment is resulting in long-term survival for most patients.

Head and Neck Cancers, Version 2.2020, NCCN Clinical Practice Guidelines in Oncology

2020-07-01

David G. Pfister , Sharon Spencer , David J. Adelstein +7 more

Treatment is complex for patients with head and neck (H&N) cancers with specific site of disease, stage, and pathologic findings guiding treatment decision-making. Treatment planning for H&N cancers involves a … Treatment is complex for patients with head and neck (H&N) cancers with specific site of disease, stage, and pathologic findings guiding treatment decision-making. Treatment planning for H&N cancers involves a multidisciplinary team of experts. This article describes supportive care recommendations in the NCCN Guidelines for Head and Neck Cancers, as well as the rationale supporting a new section on imaging recommendations for patients with H&N cancers. This article also describes updates to treatment recommendations for patients with very advanced H&N cancers and salivary gland tumors, specifically systemic therapy recommendations.

Head and neck squamous cell carcinoma

2020-11-26

Daniel E. Johnson , Barbara Burtness , C. René Leemans +3 more

Most head and neck cancers are derived from the mucosal epithelium in the oral cavity, pharynx and larynx and are known collectively as head and neck squamous cell carcinoma (HNSCC). … Most head and neck cancers are derived from the mucosal epithelium in the oral cavity, pharynx and larynx and are known collectively as head and neck squamous cell carcinoma (HNSCC). Oral cavity and larynx cancers are generally associated with tobacco consumption, alcohol abuse or both, whereas pharynx cancers are increasingly attributed to infection with human papillomavirus (HPV), primarily HPV-16. Thus, HNSCC can be separated into HPV-negative and HPV-positive HNSCC. Despite evidence of histological progression from cellular atypia through various degrees of dysplasia, ultimately leading to invasive HNSCC, most patients are diagnosed with late-stage HNSCC without a clinically evident antecedent pre-malignant lesion. Traditional staging of HNSCC using the tumour–node–metastasis system has been supplemented by the 2017 AJCC/UICC staging system, which incorporates additional information relevant to HPV-positive disease. Treatment is generally multimodal, consisting of surgery followed by chemoradiotherapy (CRT) for oral cavity cancers and primary CRT for pharynx and larynx cancers. The EGFR monoclonal antibody cetuximab is generally used in combination with radiation in HPV-negative HNSCC where comorbidities prevent the use of cytotoxic chemotherapy. The FDA approved the immune checkpoint inhibitors pembrolizumab and nivolumab for treatment of recurrent or metastatic HNSCC and pembrolizumab as primary treatment for unresectable disease. Elucidation of the molecular genetic landscape of HNSCC over the past decade has revealed new opportunities for therapeutic intervention. Ongoing efforts aim to integrate our understanding of HNSCC biology and immunobiology to identify predictive biomarkers that will enable delivery of the most effective, least-toxic therapies. Head and neck squamous cell carcinomas (HNSCCs) originate from the mucosal epithelium in the oral cavity, pharynx and larynx and are commonly associated with viral infection and tobacco use. This Primer provides an overview of the epidemiology, pathogenesis and treatment of HNSCCs of different aetiologies and the effects of the cancer and its treatment on patient quality of life.

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Nasopharyngeal carcinoma

2019-06-07

Yu‐Pei Chen , Anthony T.�C. Chan , Quynh‐Thu Le +3 more

Nasopharyngeal carcinoma

2005-06-01

WI Wei , Jonathan S. T. Sham

Administration of a Single Dose of Pembrolizumab, Docetaxel, and Cisplatin Leads to Complete Disappearance of a Locally Advanced Hypopharyngeal Squamous Cell Carcinoma: A Case Report

2025-06-25

Basil A. Alzahrani , Md Zahir Ahmed , Anas Alzahrani +2 more | Case Reports in Oncology

Introduction: Immune-checkpoint inhibition has improved the outcomes of patients with a metastatic squamous cell carcinoma in the head and neck. The combination of pembrolizumab, platinum agent, and 5-fluorouracil had been … Introduction: Immune-checkpoint inhibition has improved the outcomes of patients with a metastatic squamous cell carcinoma in the head and neck. The combination of pembrolizumab, platinum agent, and 5-fluorouracil had been shown to improve the survival of patients with a positive programmed death ligand 1 (PD-L1) test and had become the standard treatment. Patients with a high combined positive score (CPS) of >20 can be treated solely with pembrolizumab. The treatment is usually continued until disease progression. Induction immunotherapy has also shown benefits. Case presentation: We present a case of a locally advanced hypopharyngeal squamous cell carcinoma in a 63-year-old Arabic man who was started on pembrolizumab, docetaxel, and cisplatin for the first treatment cycle, but he failed to show up for the subsequent cycles due to the coronavirus disease 2019 pandemic restrictions. He came back after 10 months with complete clinical and radiological response. Conclusion: The present report may possibly be the first to report a case of locally advanced squamous cell carcinoma of the hypopharynx that showed complete clinical and radiological response to a single dose of pembrolizumab, docetaxel, and cisplatin.

Indirect comparison of TPF and GP induction chemotherapy regimens in nasopharyngeal carcinoma: a data-driven reassessment before the transition to induction chemoimmunotherapy

2025-06-24

Stefano Cavalieri , Arianna Ottini , Benedetta Lombardi Stocchetti +1 more | The Oncologist

Prognosis of Oral Cavity Cancers After Surgical Treatment: A 5-Year Retrospective Study of 80 Patients at the Maxillofacial Surgery Department of E.H.U. Oran

2025-06-24

J. Benzaoui , Hossein Karim | International Journal of Oral and Maxillofacial Surgery

Predicting Survival Outcomes of Buccal Mucosa Squamous Cell Carcinoma (BMSCC) Patients Using Dynamic Nomograms and Random Survival Forest Analysis

2025-06-24

Chao Cheng | International Journal of Oral and Maxillofacial Surgery

Total Laryngectomy in Department of Oral and Maxillofacial Surgery: A 10-Year Experience

2025-06-24

C. Enfinger , Majid Rezaei , Daniel P. Caruso +3 more | International Journal of Oral and Maxillofacial Surgery

How Has the Epidemiology of Squamous Cell Carcinoma in the Head and Neck Region Changed Over Time?

2025-06-24

Hideo Maki , Hung‐Pei Tsai | International Journal of Oral and Maxillofacial Surgery

Câncer de laringe e biomarcadores moleculares: uma revisão sistemática

2025-06-24

Barbára Mendes Paz Chao , Marciane Conti Zornita Bortolanza , Isabela Cequinel +3 more | Caderno Pedagógico

O câncer de laringe, fortemente associado ao consumo de tabaco e álcool, é uma doença de origem multifatorial, sendo o carcinoma de células escamosas seu subtipo mais comum. Apesar dos … O câncer de laringe, fortemente associado ao consumo de tabaco e álcool, é uma doença de origem multifatorial, sendo o carcinoma de células escamosas seu subtipo mais comum. Apesar dos avanços nas formas de diagnóstico e tratamento, como a radioterapia, quimioterapia e, em alguns casos, a cirurgia, as taxas de sobrevida em cinco anos permanecem estagnadas, principalmente devido à ocorrência de recidivas locais e metástases precoces. A abordagem terapêutica atual visa não apenas prolongar a sobrevida dos pacientes, mas também preservar funções vitais, como a fala, a deglutição e a respiração, essenciais para a qualidade de vida. No entanto, ainda existem lacunas importantes na detecção precoce da doença e na utilização de marcadores biológicos confiáveis para fins de previsão, diagnóstico e prognóstico. Diante desse cenário, o presente estudo realizou uma revisão sistemática da literatura científica com o objetivo de identificar e analisar os principais biomarcadores envolvidos no câncer de laringe, avaliando sua aplicabilidade clínica e seu potencial na prática oncológica.

Systematic Review of Intraoperative Radiotherapy (IORT) in Head and Neck Oncology: Past, Present, and Future Perspectives

2025-06-24

Laurence Pincet , Aurelie Fanchette , Jolanda Elmers +3 more | Cancers

Background/Objectives: Intraoperative radiotherapy (IORT) has been used for decades to improve local control in advanced and recurrent head and neck cancers by delivering a concentrated dose of radiation directly to … Background/Objectives: Intraoperative radiotherapy (IORT) has been used for decades to improve local control in advanced and recurrent head and neck cancers by delivering a concentrated dose of radiation directly to the tumor bed during surgery. Despite its potential advantages, IORT remains controversial due to its high complication rates and logistical complexity. This systematic review aims to assess the current evidence on IORT in head and neck oncology, evaluating its indications, effectiveness, and limitations. Methods: A systematic literature review was conducted in accordance with Cochrane systematic review method and reported following PRISMA guidelines. Databases, including Medline, Embase, Cochrane, and Web of Science, were searched for studies evaluating IORT in head and neck cancer. Outcomes of interest included local control rates, overall survival, complications, and treatment logistics. Data were weighted based on patient numbers, and statistical analyses included weighted means and comparative tests. Results: Included in this review are 47 studies that included 2330 patients. The studies were highly heterogeneous, limiting definitive conclusions. IORT was mainly used in stage III/IV or recurrent tumors, with an average dose of 14.7 Gy (range: 1–40 Gy). The five-year local control was 47% to 82%. Complication rates included wound necrosis (22,3%), fistulas 34 (17.8%), and carotid blow-out (14.5%). Logistical constraints remain a major limitation. Conclusions: The heterogeneous data and logistic challenges of IORT in head and neck oncology have limited its use, and the benefits remain uncertain.

Surgical Reconstructive Strategies After Major Resection in Advanced Cancer Head & Neck Patients

2025-06-24

Vedran Zubčić | International Journal of Oral and Maxillofacial Surgery

Family Medicine Physician Understanding and Management of Head and Neck Cancer Survivorship Care: A National Assessment

2025-06-24

Matthew E. Lin , Oluwatobiloba Ayo‐Ajibola , Ryan J. Davis +3 more | Annals of Otology Rhinology & Laryngology

Objectives: To understand United States family medicine physicians’ and trainees’ awareness, understanding, and confidence in following HNC survivorship guidelines. Methods: Cross-sectional survey regarding FM provider awareness of HNC survivorship guidelines. … Objectives: To understand United States family medicine physicians’ and trainees’ awareness, understanding, and confidence in following HNC survivorship guidelines. Methods: Cross-sectional survey regarding FM provider awareness of HNC survivorship guidelines. The survey was distributed to FM mailing lists and national forums. Descriptive statistics were used to characterize responses. Results: Eighty-six-physician cohort of majority attending physicians (86.1%) reporting an average of 20.0 years in practice working in non-rural (75.6%) outpatient community medical centers (41.9%). Respondents rarely cared for HNC survivors – 4.9% of patients per provider on average. They were largely unaware of the updated AHNS guidelines (8.1%). Physicians were least aware of the importance of discussing sexual intimacy/dysfunction (29%), considering pituitary dysfunction among patients with prior skull base radiation (29.1%), and evaluating for thyroid dysfunction (54.65%). Physicians were generally aware of cardiovascular disease’s impact on mortality risk (64.0%) and higher prevalence of lung cancer (60.5%) among HNC patients but were less aware of their increased risk of depression (45.4%) and suicide (39.5%). On a 5-point Likert scale, physicians endorsed high confidence in counseling about substance use cessation (mean = 3.67), screening for thyroid dysfunction (mean = 3.65), and low confidence in managing long-term effects of chemotherapy (mean = 1.48), radiotherapy (mean = 1.48), and surgery (mean = 1.47). Physicians endorsed moderate overall confidence in managing HNC patients (mean = 2.38). Conclusions: FM physicians are critical to HNC survivorship care but have a variable understanding of HNC survivorship guidelines. Increasing FM physicians’ awareness and understanding of survivorship care will help to continue improvement in HNC survivors’ quality of care and life.

In Reply to Bassi and Harris

2025-06-24

Catharine West , James M. Price , David J. Thomson | International Journal of Radiation Oncology*Biology*Physics

Personalized volume-deescalated elective nodal irradiation in oropharyngeal squamous cell carcinoma (DeEscO): a study protocol

2025-06-24

Esmée L Looman , Yoel Pérez Haas , Roman Ludwig +7 more

Abstract Background Definitive (chemo)radiotherapy of oropharyngeal squamous cell carcinoma (SCC) consists of treatment of the macroscopic tumor and prophylactic irradiation of large parts of the lymphatic drainage system: the elective … Abstract Background Definitive (chemo)radiotherapy of oropharyngeal squamous cell carcinoma (SCC) consists of treatment of the macroscopic tumor and prophylactic irradiation of large parts of the lymphatic drainage system: the elective clinical target volume (CTV). There is limited data and quantification of (occult) lymphatic spread and the required extent of the elective CTV. De-escalation of the irradiated volume could result in less early and late toxicity and less affection of the immune system. In this study, we reduce the elective CTV based on the personalized factors T-stage, clinical lymphatic involvement, and lateralization of the primary tumor. Methods The primary objective is to evaluate the efficacy and safety of an individualized de-escalation of elective node irradiation volumes. We collected a multi-institutional dataset of 598 oropharyngeal SCC patients in whom detailed lymph node involvement was reported. The data can be explored on the publicly available online platform LyProX.org. Based on the data, we developed a model of lymphatic tumor progression to estimate the probability of occult metastases in the clinically negative lymph node levels (LNLs). Metastatic lymphatic progression is described via a hidden Markov model. The patient’s state of lymph node involvement is described by hidden binary random variables, and the transition matrix describes the probabilities of lymphatic spread. Based on this model and clinical judgement, we created tables that define the personalized elective CTV for different combinations of T-stage, midline extension and clinical LNL involvement. The elective CTV is defined such that the cumulative risk of occult metastases in all non-irradiated LNLs is below 10%. The primary endpoint of this multicentric, prospective, single-arm trial is the rate of out-of-field nodal recurrences after 2 years. The study will be conducted in 6 centers across Switzerland and 120 patients will be enrolled. Discussion This study sets out to personalize the elective CTV in oropharyngeal SCC patients, with the goal to de-escalate radiotherapy for patients and herewith improve therapy-associated toxicity and quality of life. The results of this study may be used to personalize treatment in oropharyngeal SCC patients. Trial Registration This study sets out to personalize the elective CTV in oropharyngeal SCC patients, with the goal to de-escalate radiotherapy for patients and herewith improve therapy-associated toxicity and quality of life. The results of this study may be used to personalize treatment in oropharyngeal SCC patients.

Quantifying Genetic and Environmental Factors Accounting for Multistage Progression of Precancerous Lesions and Oral Cancer: Applications to Risk-Guided Prevention

2025-06-24

Donlagon Jumparway , Chiu‐Wen Su , Amy Ming‐Fang Yen +5 more | Cancers

Background: Oral squamous cell carcinoma (OSCC) is a multifactorial and multistage disease influenced by both genetic susceptibility and environmental risk factors. However, conventional oral cancer preventions are often based on … Background: Oral squamous cell carcinoma (OSCC) is a multifactorial and multistage disease influenced by both genetic susceptibility and environmental risk factors. However, conventional oral cancer preventions are often based on environmental exposures but do not allow for genetic susceptibility and both factors contributing to multistage progressions. This study developed a comprehensive multistate risk model combining both types of factors. Methods: Using data from literature, the researchers built a multistate progression model and calculated transition risks to simulate outcomes in a high-risk population, similar to those eligible for oral cancer screening in Taiwan. Results: The findings showed that OSCC risk varied dramatically across the population, ranging from 362 to over 24,000 cases per 100,000, depending on risk level. The integration of genetic and environmental risk factors into a multistate disease model allows for more accurate risk stratifications of precancerous and invasive OSCC. Frequent screening is more effective, notably in high-risk individuals. Incorporating a health education program provided an additional 2 to 6% reduction in incidence, particularly benefiting higher-risk groups. Simulation findings indicate that tailored screening strategies, particularly when combined with health education interventions, can significantly improve the effectiveness of oral cancer prevention. Conclusions: Quantifying the effects of genetic susceptibility and environmental factors on multistate natural history of precancerous lesions and oral cancer provides a valuable framework for developing the risk-guided policies for oral cancer prevention.

Independent Prognostic Significance of Worst Pattern of Invasion-5 in Oral Squamous Cell Carcinoma Patients.

2025-06-24

Ray Dang , Shih‐Chiang Huang | International Journal of Oral and Maxillofacial Surgery

Epidemiology of Oral Cancer in Southeast Asia (2000-2024) – A Systematic Review

2025-06-24

Nicholas Sim , Kai Wang | International Journal of Oral and Maxillofacial Surgery

Correlation Between Depth of Invasion and Nodal metastasis in Oral Squamous Cell Carcinoma (OSCC): Effect on Disease Free Survival and Overall Survival

2025-06-24

Prashant Kumar | International Journal of Oral and Maxillofacial Surgery

Neck management of pathological N1 oral squamous cell carcinoma: a retrospective study

2025-06-24

Z. Chen , Weidong Zhang , Xin Peng | International Journal of Oral and Maxillofacial Surgery

Impact of Technological and Therapeutic Advances on Survival Outcomes in Advanced Oral Cavity Squamous Cell Carcinoma: Insights from a Single-Center Retrospective Study

2025-06-24

Shang‐Ju Wu , Chuanle Cheng | International Journal of Oral and Maxillofacial Surgery

Correlation of High Lymph Node Yield and Patient BMI in Head and Neck Cancer

2025-06-24

Yi Chen | International Journal of Oral and Maxillofacial Surgery

Among patients with oral cavity squamous cell carcinoma does timing of adjuvant radiation therapy affect survival?

2025-06-24

Joseph S. Dillon , Andrew Che‐Fai Hui , KK Lee +2 more | International Journal of Oral and Maxillofacial Surgery

Utility of inflammation based prognostic score in oral cancer treatment

2025-06-24

K. Kubota , N Narita , Wataru Kobayashi +1 more | International Journal of Oral and Maxillofacial Surgery

Challenges in Laryngeal Cancer: Just Like the Text Books

2025-06-24

S. Alotaibi , Juan Martínez , C. Ramirez-Neyra +1 more | International Journal of Oral and Maxillofacial Surgery

Advanced Buccal Mucosa Cancer: Comprehensive Surgical Strategies in the Indian Context

2025-06-24

Sanjukta Chakraborty | International Journal of Oral and Maxillofacial Surgery

Advanced Oral Cancer Management And Its Outcome

2025-06-24

Arif Masud | International Journal of Oral and Maxillofacial Surgery

Head and Neck Cancer Risk Predictive Models: A Solution to Streamline Urgent Referrals?

2025-06-24

Meriel Fishwick , Meng Wei Ho | International Journal of Oral and Maxillofacial Surgery

Analysis of Neck Lymph Node Metastasis Patterns and Related Risk Factors in Recurrent/Ipsilateral Second Primary OSCC

2025-06-24

Changchuan Jiang | International Journal of Oral and Maxillofacial Surgery

Post Surgical Exercise to Prevent Mandibular Deviation in Partially Resected Mandible of Oral Squamous Cell Carcinoma Patients

2025-06-24

Nasir Uddin | International Journal of Oral and Maxillofacial Surgery

Textbook Outcome After Oral Cancer Surgery as a Composite Measure for Survival and Quality‐of‐Care Evaluation

2025-06-24

Hanneke Doremiek van Oorschot , Dominique V.C. de Jel , José A. Hardillo +7 more | Otolaryngology

To enhance survival outcomes for oral cavity cancer (OCC) surgery, a composite measure has been developed: "textbook outcome" (TO). Three studies have reported on this concept in OCC, but the … To enhance survival outcomes for oral cavity cancer (OCC) surgery, a composite measure has been developed: "textbook outcome" (TO). Three studies have reported on this concept in OCC, but the need for population-level results remains. This study investigates OCC surgery, focusing on survival and hospital-level results. Cohort study. National multicenter study. All first primary OCC patients who underwent curative tumor resection between 2018 and 2021 were selected from the Dutch Head and Neck Audit database. Resections were categorized as local or extensive, the latter including neck dissection and/or free or pedicled flap reconstruction. TO was defined as the absence of 30-day mortality, hospital readmission, prolonged length-of-stay, severe complications, surgical margins <1 mm, and <18 lymph nodes per side. Adjusted hazard ratios (aHRs) were determined for 2-year overall survival (OS) and disease-free survival (DFS). TO was reached in 81.1% and 46.9% after local (1039 patients) and extensive (1227 patients) resection, respectively. Reduced TO rates were observed in females, non-squamous cell carcinoma, cT3-T4, and floor of mouth compared to tongue. Obtaining TO was significantly associated with less adjuvant therapy and improved 2-year survival after local (aHR 0.55 OS P = .004, 0.70 DFS P = .085) and extensive (aHR 0.61 OS P ≤ .001, 0.69 DFS P = .002) surgery. After correction for population differences, no interhospital variation in TO remained. Achieving TO is strongly linked to improved survival, highlighting its importance as a short-term composite quality-of-care indicator. The separate outcomes that were influential to the hospital's TO score differed between hospitals, indicating opportunities to improve outcomes.

Depth of Invasion Evaluation in Tongue Squamous Cell Carcinoma with Head and Neck MRI

2025-06-24

Han‐Yi Chou , Hong-Jian Cheng | International Journal of Oral and Maxillofacial Surgery

Investigation of prognostic factors of oral cancer using skeletal muscle mass and inflammation-based prognostic scores

2025-06-24

Emiko Yamasaki , Sachiko Yamasaki , Mirai Higaki +5 more | International Journal of Oral and Maxillofacial Surgery

Induction Chemotherapy with or without Radical Surgery for Advanced Stage IVb Oral Cancer: A 7-Year Experience at National Taiwan University Hospital

2025-06-24

Li-Chi Chiang , Edward Y. Cheng | International Journal of Oral and Maxillofacial Surgery

Analysis of Predictors of Recurrence in Patients with Oral Cavity Squamous Cell Carcinoma After Surgical Treatment

2025-06-24

Valéria Maria Prado Barreto , A. González Jiménez , N. Vieira Sebe +7 more | International Journal of Oral and Maxillofacial Surgery

Correlation of Depth of Invasion in Early Stage Oral Cavity Squamous Cell Carcinoma

2025-06-24

Sahal Alotaibi , C. Ramirez-Neyra , Y. Al-Riyami +1 more | International Journal of Oral and Maxillofacial Surgery

Gender-, Age-, and Tumor Stage-Dependent Changes in Daily Mobility After Surgical Treatment of Oral Cavity Carcinoma: A Retrospective Analysis of 100 Patients

2025-06-24

Myla Ebeling | International Journal of Oral and Maxillofacial Surgery

Risk of Second Primary Cancer in Patients with Head and Neck Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis

2025-06-24

Liang Yang | International Journal of Oral and Maxillofacial Surgery

Outcomes of Selective Neck Dissection in Oral Cancer Surgery: A Prognostic Evaluation

2025-06-24

Hoon Park | International Journal of Oral and Maxillofacial Surgery

Three-Dimensional Analysis of Volumetric Change of Oral Cancer Following Neoadjuvant Chemotherapy

2025-06-24

Wook Nam | International Journal of Oral and Maxillofacial Surgery

A Novel Metastatic Propensity Grading System as a Research Tool in Head & Neck Squamous Cell Carcinomas (HNSCC)

2025-06-24

Jonathan J. Hue , Lorenzo Veschini , Selvam Thavaraj | International Journal of Oral and Maxillofacial Surgery

The Association of HBV Infection and Head and Neck Cancer: A Systematic Review and Meta-Analysis

2025-06-24

Yang Luo | International Journal of Oral and Maxillofacial Surgery

Investigation of Lingual Inclination of Dental Axes in Patients with Tongue Cancer

2025-06-24

Jumpei Tanaka , Takafumi Satomi | International Journal of Oral and Maxillofacial Surgery

Predictive Value of ACE 27 Tool for Surgical Outcomes in Geriatric Head and Neck Cancer in the Indian Subcontinent

2025-06-23

Amit Kumar , Rajeev Kumar , Rachit Sood +7 more | Indian Journal of Otolaryngology and Head & Neck Surgery

Editorial: Challenges to research on oral potentially malignant disorders and oral cancer

2025-06-23

Alberto Rodríguez-Archilla , Luis Alberto Gaitán-Cepeda | Frontiers in Oncology

Radiation Dose Effects on Salivary Gland Function in Head and Neck cancer patients- A Prospective Study

2025-06-23

K V Apoorva , Vijendra Shenoy , Rabia Suzanne Angiras +5 more | Indian Journal of Otolaryngology and Head & Neck Surgery

Optimal induction chemotherapy courses in nasopharyngeal carcinoma in the IMRT era: Comment

2025-06-23

Hinpetch Daungsupawong , Viroj Wiwanitkit | Oral Oncology

Head and Neck Examinations Among Patients Presenting to <scp>HRSA</scp>‐Funded Health Centers in the United States

2025-06-23

Leah I. Leinbach | Journal of Public Health Dentistry

Health centers funded by the Health Resources and Services Administration (HRSA) are a safety net for people who may not be able to access care elsewhere. Patients eligible for care … Health centers funded by the Health Resources and Services Administration (HRSA) are a safety net for people who may not be able to access care elsewhere. Patients eligible for care at these facilities share some of the same risk factors for developing head and neck cancer. The objective of this study is to examine the prevalence of head and neck cancer examinations among patients of HRSA-funded health centers. This is an analysis of the cross-sectional 2022 Health Center Patient Survey (HCPS). Self-reported data from this survey of patients of health centers regarding receipt of head and neck examinations is summarized, with results stratified by sociodemographic, behavioral, and health-related factors. Four thousand four hundred and fourteen unweighted patients (20,693,940 weighted) participated in the HCPS, 69.5% of whom answered questions about a head and neck exam. Of these, 9.9% of patients reported a history of a head and neck exam (HNE). Patients from minoritized racial/ethnic groups were less likely to report an HNE compared to White, non-Hispanic patients. Patients with Medicare, Medicaid, and lower incomes were also less likely to report an HNE compared to patients with private insurance and incomes above $50,000 per year. A dental exam anywhere within the last year was associated with a report of an HNE. Disparities in reported HNEs were observed by patient race/ethnicity, medical payor, income, and recency of dental visit among patients of US health centers. Health centers may be uniquely positioned to explore and generate evidence regarding HNEs that could inform changes in practice.

Oral cancer awareness among dentists: what is missing? A cross-sectional study

2025-06-22

Dalia Ghalwash , Fatheya Zahran | Journal of the Egyptian National Cancer Institute

Abstract Introduction Oral cancer (OC) is one of the major global health problems with a high incidence rate in developing countries. Early detection can improve the prognosis and survival rate … Abstract Introduction Oral cancer (OC) is one of the major global health problems with a high incidence rate in developing countries. Early detection can improve the prognosis and survival rate of the disease. Aim The current study evaluates dentists’ general awareness, knowledge, attitude, and practice regarding oral cancer. Methods In the current cross-sectional study, a self-reported questionnaire was distributed to a sample of dentists in Egypt. A total of 700 dentists participated. The questionnaire included 27 questions on oral cancer knowledge, opinions, attitudes, and practices. Results The highest awareness of risk factors concentrated around tobacco and alcohol consumption, and the most acknowledged clinical presentations were non-healing ulcers, red lesions, white lesions, and induration. The tongue was considered a high-risk site by 69% of participants, followed by the floor of the mouth and the buccal/lip mucosa. Only 37% of the participants carried out proper clinical screening for OC, while only 31% carried out routine lymph node examinations. Sixty-six percent of participants considered themselves incompetent regarding detection of OC. Ninety-two percent of participants acknowledged the important role of dentists in the early detection of oral cancer, and 99% of them thought that oral cancer awareness campaigns are needed and would be effective. Awareness was significantly associated with years of practice. Conclusion Awareness regarding OC among the Egyptian dentists participating in the current survey showed definitive defects. Hence, efforts to raise awareness of OC among dental practitioners are an important factor in improving/early detection of OC, with the resultant increase in survival rate and decrease in morbidity. This can be reached only through more solid undergraduate syllabi and training as well as workshops and campaigns.

Chronic Hypoxia Due to Hypopharyngeal Cancer Presenting As Generalized Weakness: A Case Report

2025-06-22

Ryunosuke Hashikawa , Akira Kuriyama , Takao Terai +1 more | Cureus

THE EFFECT OF NEOADJUVANT THERAPY IN THE TREATMENT OF HEAD AND NECK TUMORS USING PROTON RADIATION THERAPY

2025-06-22

Alexey Vladimirovich Nezvetskiy , Irina Valeryevna Nezvetskaya , Yuri Dmitrievich Dmitrievich | Journal of clinical practice

The aim of the study was to evaluate the effect of induction drug therapy on the treatment outcomes of patients with locally advanced tumors of the head and neck who … The aim of the study was to evaluate the effect of induction drug therapy on the treatment outcomes of patients with locally advanced tumors of the head and neck who received radiation treatment using proton therapy, IMPT technique. Methods. The retrospective study included an analysis of the medical records of 103 patients with head and neck tumors, who were divided into two groups: patients who received induction chemotherapy followed by proton chemoradiotherapy (I+CPLT) (n=50), and patients who did not receive induction antitumor treatment before starting proton chemoradiotherapy (CPLT) (n=53). T-tests for independent samples were used to assess differences between patient groups. The statistical significance of the differences was considered at a level of p 0.05. Results. The median follow–up was 13.4 months (IQR: 11.6-21.6 months). The average follow-up time was 15.7 ± 7.8 months. In the group of monitored patients, none interrupted planned treatment, and therapy was completed on time. In the IPHLT group, the average OS was 27.65 months (95% CI: 24.46 – 30.85), while for the PHLT groups it was 27.27 months (95% CI: 22.15 – 31.72), which was a statistically insignificant difference (Chi-squared = 0.776, p = 0.378). The median OS for both study groups was not reached. The progression–free survival assessment showed that the average time to progression in the IPHLT group was 23.1 months (95% CI: 19.6 – 26.6), versus 21.2 months (95% CI: 16.7 - 25.7) in the PHLT group. The incidence of grade 1 leukopenia was 30% in the IPHLT group versus 20.8% in the PHLT group, the incidence of grade 3 disorders was 26% in the IPHLT group and 11.3% in the PHLT group, and grade 3 complications were noted only in the IPHLT group (12%). These differences are statistically significant (p0.01). Conclusion. This study demonstrated that induction chemotherapy does not improve overall survival and progression-free survival in patients with locally advanced squamous cell carcinoma of the head and neck receiving proton chemoradiotherapy.

Utilising remote imaging consultation for the early detection of oral cancer: a case series and pilot study

2025-06-21

Nobuyuki Kaibuchi , Akira Shimasaki , Masaki Ikeda +3 more | Oral and Maxillofacial Surgery

Comparative efficacy of p16 versus HPV RNA in situ hybridization in oropharyngeal squamous cell carcinomas

2025-06-21

Ebenezer Amarachukwu Okoh | World Journal of Advanced Research and Reviews

The accurate determination of human papillomavirus (HPV) status in oropharyngeal squamous cell carcinoma (OPSCC) has profound prognostic and therapeutic implications. As the incidence of HPV-associated OPSCC continues to rise globally, … The accurate determination of human papillomavirus (HPV) status in oropharyngeal squamous cell carcinoma (OPSCC) has profound prognostic and therapeutic implications. As the incidence of HPV-associated OPSCC continues to rise globally, particularly in developed nations, the need for precise, reliable biomarkers to distinguish HPV-driven malignancies has become increasingly critical. While p16 immunohistochemistry (IHC) has long served as a surrogate marker for HPV involvement, concerns over its specificity given its ability to overexpress in HPV-negative tumors have prompted interest in more direct molecular assays. Among these, HPV RNA in situ hybridization (ISH) offers a promising technique capable of detecting transcriptionally active viral RNA within the tumor microenvironment, directly reflecting oncogenic activity. This study conducts a comparative analysis of p16 IHC and HPV RNA ISH in a cohort of OPSCC patients, examining concordance rates, diagnostic sensitivity and specificity, and their association with clinical outcomes such as overall survival and recurrence-free interval. While p16 IHC maintains high sensitivity and remains cost-effective, RNA ISH demonstrates superior specificity and a closer correlation with disease progression and patient stratification in treatment protocols. Our results reveal discordance in a subset of cases, underscoring the limitations of relying solely on p16 status for clinical decision-making. Incorporating both assays in a dual-testing algorithm may optimize diagnostic accuracy, enhance prognostic stratification, and better inform tailored therapeutic strategies. The findings highlight the importance of nuanced biomarker selection in HPV-driven head and neck cancers and advocate for standardized molecular pathology workflows that integrate both surrogate and direct detection modalities.