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Human papillomavirus-associated (HPV+) head and neck squamous cell carcinoma (HNSCC) is the most common HPV-associated cancer in the United States, with a rapid increase in incidence over the last two decades. The burden of HPV+ HNSCC is likely to continue to rise, and given the long latency between infection and the development of HPV+ HNSCC, it is estimated that the effect of the HPV vaccine will not be reflected in HNSCC prevalence until 2060. Efforts have begun to decrease morbidity of standard therapies for this disease, and its improved characterization is being leveraged to identify and target molecular vulnerabilities. Companion biomarkers for new therapies will identify responsive tumors. A more basic understanding of two mechanisms of HPV carcinogenesis in the head and neck has identified subtypes of HPV+ HNSCC that correlate with different carcinogenic programs and that identify tumors with good or poor prognosis. Current development of biomarkers that reliably identify these two subtypes, as well as biomarkers that can detect recurrent disease at an earlier time, will have immediate clinical application. [ABSTRACT FROM AUTHOR]

Background: Human papillomavirus–positive (HPV+) squamous cell carcinoma of the oropharynx (OPSCC) is the most prevalent HPV‐associated malignancy in the United States. Favorable treatment outcomes have led to increased interest in treatment de‐escalation to reduce treatment morbidity as well as the development of prognostic markers to identify appropriately low‐risk patients. Intratumoral genomic heterogeneity and copy number alteration burden have been demonstrated to be predictive of poor outcomes in many other cancers; therefore, we sought to determine whether intratumor heterogeneity and genomic instability are associated with poor outcomes in HPV+ OPSCC. Methods: Tumor heterogeneity estimates were made based on targeted exome sequencing of 45 patients with HPV+ OPSCC tumors. Analysis of an additional cohort of HPV+ OPSCC tumors lacking matched normal sequencing allowed copy number analysis of 99 patient tumors. Results: High intratumorally genomic heterogeneity and high numbers of copy number alterations were strongly associated with worse recurrence‐free survival. Tumors with higher heterogeneity and frequent copy number alterations were associated with loss of distal 11q, which encodes key genes related to double‐strand break repair, including ATM and MRE11A. Conclusions: Both intratumor genomic heterogeneity and high‐burden copy number alterations are strongly associated with poor recurrence‐free survival in patients with HPV+ OPSCC. The drivers of genomic instability and heterogeneity in these tumors remains to be elucidated. However, 11q loss and defective DNA double‐strand break repair have been associated with genomic instability in other solid tumors. Copy number alteration burden and intratumoral heterogeneity represent promising avenues for risk stratification of patients with HPV+OPSCC. Molecular markers are needed to determine which human papillomavirus (HPV)‐positive patients with squamous cell carcinoma of the oropharynx (OPSCC) are best served by reduced intensity treatment, which has the potential to reduce severe treatment‐related morbidity. We demonstrate that 11q‐related copy number variant burden and heterogeneity are highly associated with poor recurrence‐free survival in patients with HPV‐positive OPSCC and may have potential as translational biomarkers. [ABSTRACT FROM AUTHOR]

Purpose: To assess the prevalence and predictors of mental health disorders (MDHs) among head and neck squamous cell carcinoma (HNSCC) survivors, and the association with health-related quality of life (HRQOL), pain, and survival outcomes., Materials and Methods: This was a retrospective, cross-sectional study of HNSCC survivors surveyed at an outpatient oncology clinic from May 2012 through July 2016., Results: Among 198 HNSCC survivors, 21% reported a MHD. Female sex (OR 6.60, 95% CI 2.08 to 20.98; p = 0.001) and Medicare insurance status (OR 4.95, 95% CI 1.52 to 16.11; p = 0.008) were significant predictors of reporting a MHD in the fully adjusted model. Patients reporting a MHD reported significantly worse pain (p < 0001) and worse HRQOL on the PROMIS Physical (p < 0.001), PROMIS Mental (p < 0.001), and FACT-GP (p < 0.026) questionnaires. Diagnosis of a MHD was not correlated with 5-year OS (74% vs. 84%; p = 0.087)., Conclusion: Initiatives for early identification and intervention of MHDs as part of survivorship initiatives may engender clinically meaningful outcomes in head and neck cancer., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives/hypothesis: The current state of the U.S. public's knowledge of the relationship between human papillomavirus (HPV) and HPV vaccinations to oropharyngeal squamous cell carcinoma (OPSCC) is unknown. Our objective was to 1) assess the general population's knowledge of human papillomavirus (HPV) and willingness to vaccinate, and 2) assess whether targeted education on HPV-related OPSCC can change intentions to vaccinate., Study Design: Online cross-sectional survey., Methods: An online, cross-sectional survey utilizing U.S. census-derived quotas to represent the U.S. population was distributed and analyzed to 517 adults in 2020., Results: Exactly 72.7% of participants stated that they had or would vaccinate their child against HPV and were designated as "vaccinators." In multivariate regression, Black individuals were less likely to be vaccinators (OR 0.51 [95% CI 0.27-0.94]), but those who were aware of HPV's role in OPSCC were more likely to vaccinate (OR 2.56 [95% CI 1.47-4.46]). Knowledge about vaccination side-effects, eligibility, and mechanisms of HPV spread was low. Only 30.6% of the sample reported understanding the role of HPV in OPSCC. Of these, 43.0% gained this knowledge exclusively from nonhealthcare professional sources, like television. When presented with four short HPV-OPSCC-centered facts (HPV's role in OPSCC etiology, prevalence of infection, clinically silent course, and vaccine preventative effects), 54.0% of "nonvaccinators" indicated a willingness to change their minds., Conclusions: General knowledge about HPV, HPV's role in OPSCC, and the vaccine remains low in the general population. There are racial disparities in willingness to vaccinate within this sample, but these may be overcome by effective education on HPV-related OPSCC., Level of Evidence: 3 Laryngoscope, 132:528-537, 2022., (© 2021 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: To assess knowledge regarding head and neck cancers (HNCs) in 2020, factors associated with knowledge of the role of human papillomavirus (HPV) in HNCs, and factors associated with exposure to Oral, Head and Neck Cancer Awareness Week (OHANCAW)., Study Design: Cross-sectional survey., Setting: Online., Methods: The survey was distributed to 517 participants via a paid panel and utilized US Census-built quotas to represent the US population., Results: Participants surpassed 50% awareness rates in only 5 of 10 (50.0%), 2 of 6 (33.3%), and 5 of 9 (55.5%) preselected answer choices for subsites, risk factors, and signs/symptoms of HNCs, respectively. Knowledge of HPV's role in oropharyngeal cancer was also low, at 30.6%. However, of the controlled variables, exposure to OHANCAW was closely associated with knowledge of HPV's role in HNC (odds ratio, 10.25; 95% CI, 5.36-19.62). Women and elderly individuals were less likely to be exposed to OHANCAW, while those with higher education, those who drink heavily (>4 drinks/d), and current but not former tobacco users were more likely to be exposed., Conclusions: Knowledge of HNCs and the causal role of HPV remains suboptimal, though our results suggest that OHANCAW remains a viable educational pathway. However, certain at-risk populations, such as former smokers and older individuals, whom we may not be effectively reaching and screening, represent a priority for future outreach efforts.

Objectives: To compare long-term oncologic outcomes and adjuvant therapies for patients treated with transoral robotic surgery (TORS), nonrobotic surgery, or transoral laser microsurgery (TLM)., Study Design: A retrospective analysis of the National Cancer Database (2010-2014)., Methods: Patients with clinical tumor (T)1 and T2 oropharyngeal squamous cell carcinomas (OPSCC) were classified into those receiving TORS versus nonrobotic surgery versus TLM. Univariate and multivariate survival analyses were conducted with chi-square tests; Kaplan-Meier log-rank test; and Cox multivariate, logistic regression, and multinomial regression modeling., Results: We identified 2,224 OPSCC TORS patients; 6,697 nonrobotic surgery patients; and 333 TLM patients. The majority of patients were white males with a mean age of approximately 59 years. No significant difference was noted between the cohorts in tumor stage; however, TORS patients were more likely to have nodal (N)1 to N3 disease than nonrobotic surgery and TLM patients, respectively (69.8% vs. 62.0% vs. 59.7%, P < 0.001). TORS was associated with a lower likelihood of positive margins when compared to nonrobotic surgery, although not TLM (nonrobotic surgery: hazard ratio [HR] 1.51, P < 0.001, TLM: HR 1.13, P = 0.582). TORS was associated with lower likelihood of postsurgical chemoradiotherapy (TLM: HR 2.07, P < 0.001, nonrobotic surgery: 1.65, P < 0.001) but not adjuvant radiotherapy alone (TLM: HR 1.06, P = 0.569, nonrobotic surgery: 0.96, P = 0.655). On multivariate Cox analysis of overall survival, the use of TORS was not associated with increased survival (TLM: HR 1.31, P = 0.233, nonrobotic surgery: HR 1.12, P < 0.303)., Conclusion: The advantages of TORS for early-stage OPSCC may be a lower likelihood of postsurgical positive margins and subsequent need for adjuvant chemoradiotherapy., Level of Evidence: NA Laryngoscope, 129:1844-1855, 2019., (© 2018 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Evidence surrounding the effect of adjuvant treatment in salivary gland cancers is limited. The benefit of adding chemotherapy to adjuvant treatment is also of interest. We investigated the association of these treatments with survival and whether this differed by stage or the presence of adverse features., Methods: A retrospective study of adult salivary gland cancer cases diagnosed from 2004 to 2013 in the National Cancer Data Base (NCDB) was conducted., Results: Treatment with adjuvant radiotherapy was associated with improved survival for both patients with early-stage (hazard ratio [HR] 0.744; P = .004) and late-stage (HR 0.688; P < .001) disease with adverse features. Further addition of chemotherapy to the adjuvant treatment of patients with late-stage disease with adverse features was not associated with a survival benefit (HR 1.028; P = .705)., Conclusion: Adjuvant radiotherapy is associated with improved survival for patients with adverse features, regardless of stage. The addition of chemotherapy to the adjuvant treatment of patients with late-stage disease with adverse features is not associated with improved outcomes., (© 2018 Wiley Periodicals, Inc.)

Objective After radiation failure for early T-stage larynx cancer, national guidelines recommend salvage surgery. Total laryngectomy and conservation laryngeal surgery with an open or endoscopic approach are both used. Beyond single-institution studies, there is a lack of evidence concerning the outcomes of these procedures. We aim to study whether treatment with conservation laryngeal surgery is associated with poorer outcomes than treatment with total laryngectomy as salvage surgery after radiation failure for T1/T2 larynx cancers. Study Design A retrospective study was conducted of adult squamous cell larynx cancer cases in the National Cancer Database diagnosed from 2004 to 2012. Setting Commission on Cancer cancer programs in the United States. Methods Demographic, facility, tumor, and survival variables were included in the analyses. Multivariate survival regressions as well as univariate Kaplan-Meier analyses were conducted. Results Slightly more than 7% of patients receiving radiotherapy for T1/T2 larynx cancers later received salvage surgery. Salvage with partial laryngectomy was not associated with diminished survival as compared with total laryngectomy. However, positive surgical margins were associated with worse outcomes (hazard ratio, 1.782; P = .001), and a larger percentage of patients receiving partial laryngectomy had positive margins than those receiving total laryngectomy. Facility characteristics were not associated with differences in salvage surgery type or outcomes. Conclusion In recognition of the inherent selection bias, patients who experienced recurrences after radiation for T1/T2 larynx cancer and underwent conservation salvage laryngeal surgery demonstrated clinical outcomes similar to those of patients undergoing salvage total laryngectomy. Increased rates of positive surgical margins were observed among patients undergoing salvage conservation surgery.

Background: Treatment durations and factors associated with delays for oral cavity squamous cell carcinoma (SCC) have previously been described but are not fully understood. Impact of delays on overall survival (OS) remains unclear., Methods: The National Cancer Data Base (NCDB) was used to analyze 4868 patients with oral cavity SCC from 1998 to 2011. Diagnosis-to-surgery, surgery-to-radiotherapy (RT) start , RT duration, total treatment package (surgery-to-RT end ), and diagnosis-to-RT end were evaluated. Associations between delays and various factors were analyzed using binary logistic regression. Associations with OS were analyzed using the Cox proportional hazards model., Results: Medians for diagnosis-to-surgery, surgery-to-RT start , RT duration, total treatment package, and diagnosis-to-RT end were 30, 50, 49, 101, and 136 days, respectively. Age ≥60 years, uninsured or Medicaid insurance, comorbidity, late pT, and treatment at an academic/research institution were associated with diagnosis-to-surgery delays. Only delays in RT duration were significantly associated with decreased OS (hazard ratio [HR] = 1.21; p = .02)., Conclusion: Numerous factors are associated with treatment delays. RT duration is significantly associated with OS. © 2017 Wiley Periodicals, Inc. Head Neck 39: 639-646, 2017., (© 2017 Wiley Periodicals, Inc.)

Background: The current study was performed to characterize trends and survival outcomes for chemotherapy in the definitive and adjuvant treatment of hypopharyngeal cancer in the United States., Methods: A total of 16,248 adult patients diagnosed with primary hypopharyngeal cancer without distant metastases between 1998 and 2011 were identified in the National Cancer Data Base. The association between treatment modality and overall survival was analyzed using Kaplan-Meier survival curves and 5-year survival rates. A multivariate Cox regression analysis was performed on a subset of 3357 cases to determine the treatment modalities that predict improved survival when controlling for demographic and clinical factors., Results: There was a significant increase in the use of chemotherapy with radiotherapy both as definitive treatment (P<.001) and as adjuvant chemoradiotherapy with surgery (P=.001). This was accompanied by a decrease in total laryngectomy/pharyngectomy rates (P<.001). Chemoradiotherapy was associated with improved 5-year survival compared with radiotherapy alone in the definitive setting (31.8% vs 25.2%; log rank P<.001). Similarly, in multivariateanalysis, definitive radiotherapy was found to be associated with compromised survival compared with definitive chemoradiotherapy (hazard ratio, 1.51; P<.001)., Conclusions: Survival analysis revealed that overall 5-year survival rates were higher for chemoradiotherapy compared with radiotherapy alone in the definitive setting, but were comparable between surgery with chemoradiotherapy and surgery with radiotherapy. Cancer 2016;122:1853-60. © 2016 American Cancer Society., (© 2016 American Cancer Society.)

Objectives/hypothesis: The objective was to characterize incidence, treatment, and survival for hypopharyngeal cancer in the United States between 1988 and 2010, and to analyze associations between changes in treatment modality and survival., Study Design: Retrospective cohort study., Methods: A total of 3,958 adult patients with hypopharyngeal cancer were identified in the Surveillance, Epidemiology, and End Results database. Incidence, treatment, and survival, controlling for patient demographics and disease severity, were analyzed using two-tailed t tests, Kaplan-Meier analysis, and univariate and multivariate Cox regression., Results: The incidence of hypopharyngeal cancer decreased from 1973 to 2010 with an average annual percent change (APC) of -2.0% every year (P < .05). Treatment with laryngopharyngectomy decreased (-2.5% APC, P < .001), treatment with radiotherapy without surgery increased (+2.0% APC, P < .001), and treatment with neither surgery nor radiotherapy increased (+0.5% APC, P < .001) between 1988 and 2010. There was a significant increase in the 5-year overall survival between 1988 and 1990 and between 1991 and 1995 (P = .024) with no other significant temporal trends in survival. Multivariate analysis revealed that age (65-74, 75-84, or 85+ relative to 18-54 years old), race (white relative to non-African races), T stage (T2, T3, or T4 relative to T1), N stage (N2 or N3 relative to N0), and treatment modality (-surgery/-radiation, -surgery/+radiation, and +surgery/-radiation relative to +surgery/+radiation) were all significantly associated with worse survival., Conclusions: Hypopharyngeal cancer has had a decreasing incidence with little change in patient or tumor characteristics. Treatment has increasingly involved radiation without laryngopharyngectomy. This has not been associated with a decrease in survival. Controlling for patient demographics and disease severity, radiation with laryngopharyngectomy is associated with improved survival., (© 2014 The American Laryngological, Rhinological and Otological Society, Inc.)

Importance: Head and neck cancer (HNC) is responsible for substantial morbidity, mortality, and cost in the United States. Early detection and lifestyle risk factors associated with HNC, both determinants of disease burden and outcomes, are interrelated with public knowledge of this disease. Understanding of current public knowledge of HNC is lacking., Objective: To assess awareness and knowledge of HNC among US adults., Design, Setting, and Participants: Online survey of 2126 randomly selected adults in the United States conducted in 2013., Interventions: Online survey administration., Main Outcomes and Measures: Subjective and objective assessment of knowledge of HNC including symptoms, risk factors, and association with the human papillomavirus., Results: Self-reported respondent knowledge of HNC was low, with 66.0% reporting that they were "not very" or "not at all" knowledgeable. This did not vary significantly with tobacco use (P = .92), education (P = .053), sex (P = .07), or race (P = .02). Regarding sites comprising HNC, 22.1% of respondents correctly identified throat cancer, 15.3% mouth cancer, and 2.0% cancer of the larynx, with 21.0% incorrectly identifying brain cancer as HNC. Regarding symptoms, 14.9% of respondents identified "red or white sores that do not heal," 5.2% "sore throat," 1.3% "swelling or lump in the throat," and 0.5% "bleeding in the mouth or throat." Smoking and chewing or spitting tobacco were identified by 54.5% and 32.7% of respondents as risk factors for mouth and throat cancer, respectively. Only 0.8% of respondents identified human papillomavirus (HPV) infection as a risk factor for mouth and throat cancer, but specific questioning revealed that 12.8% were aware of the association between HPV infection and throat cancer whereas 70.0% of respondents were aware of the vaccine targeting HPV., Conclusions and Relevance: Self-reported and objective measures indicate that few American adults know much about HNC including risk factors such as tobacco use and HPV infection and common symptoms. Strategies to improve public awareness and knowledge of signs, symptoms, and risk factors may decrease the disease burden of HNC and are important topics for future research.