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BACKGROUND: Human papillomavirus (HPV) is responsible for a growing proportion of oropharyngeal squamous cell carcinomas (OPSCCs) among men and White individuals. Whether similar trends apply to women, non‐Whites, and non‐oropharyngeal squamous cell carcinomas (non‐OPSCCs) is unknown. METHODS: This is a cross‐sectional analysis combining 2 multi‐institutional case series of incident head and neck squamous cell carcinoma (HNSCC) cases. Incident HNSCCs from 1995 to 2012 were enrolled retrospectively using banked tumor samples and medical record abstraction. Incident HNSCCs from 2013 to 2019 were enrolled prospectively. The prevalence of tumor HPV biomarkers was tested over 3 time periods (1995‐2003, 2004‐2012, and 2013‐2019). Centralized testing was done for p16 immunohistochemistry (p16) and oncogenic HPV in situ hybridization (ISH). RESULTS: A total of 1209 incident cases of HNSCC were included. Prevalence of p16‐ and ISH‐positive tumors increased significantly for oropharynx cancers over time. The majority were positive after 2013 for White patients (p16, 92%; P <.001; ISH 94%; P <.001), Black patients (p16, 72%; P =.021; ISH 67%; P =.011), and Hispanic patients (p16, 100%; P =.04; ISH 100%; P =.013). For women with OPSCC, the prevalence of p16‐ and ISH‐positive tumors increased significantly to 82% (P <.001) and 78% (P =.004), respectively. For non‐OPSCCs, there was increased p16 and ISH positivity overall with 24% p16 and 16% ISH positivity in the most recent time period (P <.001 for both). CONCLUSIONS: The majority of OPSCCs in US tertiary care centers are now p16 and ISH positive for all sex and race groups. In some populations in the United States, 91% of OPSCCs are now caused by HPV. Few non‐OPSCCs are p16 and ISH positive. This study evaluates the prevalence of p16 and in situ hybridization positivity in head and neck cancers over time. This study shows an increase in prevalence over time among women and non‐Whites, 2 groups that are understudied in the epidemiology of human papillomavirus. [ABSTRACT FROM AUTHOR]

Background: Recursive partitioning analysis (RPA) from the Radiation Therapy Oncology Group (RTOG)‐0129 has identified a low‐risk group of patients with oropharynx cancer (OPC) who might benefit from therapeutic de‐intensification. These risk groups have not yet been reproduced in an independent cohort treated heterogeneously. Therefore, the objective of this analysis was to validate the RPA risk groups and examine the prognostic impact of novel factors. Methods: Patients with OPC were enrolled in a prospective study at 3 academic medical centers from 2013 to 2018. Medical record abstraction was used to ascertain clinical variables including staging and survival according to the 7th edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual. Human papillomavirus–positive tumor status was determined by p16 immunohistochemistry and/or HPV RNA in situ hybridization. Kaplan‐Meier and log‐rank methods were used to compare survival. Cox proportional hazards were used to generate univariate and multivariable hazard ratios (HRs). Results: Median follow‐up time was 3.2 years. The low‐, intermediate‐, and high‐risk groups had significant differences in 2‐year overall survival (OS, 99.1%; 95% CI, 94.4%‐99.9% vs OS, 93.0%; 95% CI, 74.7%‐98.2% vs OS, 80.0%; 95% CI, 40.9%‐94.6%; Poverall =.0001) and 2‐year progression‐free survival (PFS, 97.5%; 95% CI, 92.4%‐99.2% vs PFS, 89.3%; 95% CI, 70.3%‐96.4% vs PFS, 80.0%; 95% CI, 40.9%‐94.6%; Poverall <.002). After adjustment for age, sex, and level of educational attainment, OS and PFS were significantly lower for the intermediate‐ (OS adjusted hazard ratio [aHR], 5.0; 95% CI, 1.0‐23.0; PFS aHR, 3.4; 95% CI, 1.0‐11.5), and high‐ (OS aHR, 7.3; 95% CI, 1.4‐39; PFS aHR, 5.0; 95% CI, 1.2‐21.6) risk groups compared with the low‐risk group. Lower education was also independently significantly associated with worse OS (aHR, 8.9; 95% CI, 1.8‐44.3) and PFS (aHR, 3.1; 95% CI, 1.0‐9.6). Conclusions: In patients with OPC, the RTOG‐0129 RPA model is associated with OS and PFS in a heterogeneously treated cohort. In patients with oropharyngeal squamous cell carcinoma (OPC), the Radiation Therapy Oncology Group (RTOG)‐0129 recursive partitioning analysis model is associated with overall survival and progression‐free survival in a heterogeneously treated cohort. It is the hope that this study will contribute to identifying favorable, low‐risk patients with therapeutic implications for treatment de‐intensification in future clinical trials for OPC. [ABSTRACT FROM AUTHOR]

Background: Case‐control studies from the early 2000s demonstrated that human papillomavirus–related oropharyngeal cancer (HPV‐OPC) is a distinct entity associated with number of oral sex partners. Using contemporary data, we investigated novel risk factors (sexual debut behaviors, exposure intensity, and relationship dynamics) and serological markers on odds of HPV‐OPC. Methods: HPV‐OPC patients and frequency‐matched controls were enrolled in a multicenter study from 2013 to 2018. Participants completed a behavioral survey. Characteristics were compared using a chi‐square test for categorical variables and a t test for continuous variables. Adjusted odds ratios (aOR) were calculated using logistic regression. Results: A total of 163 HPV‐OPC patients and 345 controls were included. Lifetime number of oral sex partners was associated with significantly increased odds of HPV‐OPC (>10 partners: odds ratio [OR], 4.3 [95% CI, 2.8‐6.7]). After adjustment for number of oral sex partners and smoking, younger age at first oral sex (<18 vs >20 years: aOR, 1.8 [95% CI, 1.1‐3.2]) and oral sex intensity (>5 sex‐years: aOR, 2.8 [95% CI, 1.1‐7.5]) remained associated with significantly increased odds of HPV‐OPC. Type of sexual partner such as older partners when a case was younger (OR, 1.7 [95% CI, 1.1‐2.6]) or having a partner who had extramarital sex (OR, 1.6 [95% CI, 1.1‐2.4]) was associated with HPV‐OPC. Seropositivity for antibodies to HPV16 E6 (OR, 286 [95% CI, 122‐670]) and any HPV16 E protein (E1, E2, E6, E7; OR, 163 [95% CI, 70‐378]) was associated with increased odds of HPV‐OPC. Conclusion: Number of oral sex partners remains a strong risk factor for HPV‐OPC; however, timing and intensity of oral sex are novel independent risk factors. These behaviors suggest additional nuances of how and why some individuals develop HPV‐OPC. This comprehensive behavioral case‐control study of human papillomavirus (HPV)‐related oropharyngeal cancer reveals that oral sex and number of partners remain strong risk factors for HPV‐related oropharyngeal cancer. Measures of oral sexual behavior—including early age and intensity of exposure—are independent risk factors, suggesting that these behaviors may explain additional nuances of how and why some individuals develop HPV‐related oropharyngeal cancer. [ABSTRACT FROM AUTHOR]

Background: The incidence of oropharyngeal squamous cell carcinoma (OPSCC) is increasing among older adults. It is unknown whether these trends can be explained by human papillomavirus (HPV) and whether HPV-related tumors remain associated with an improved prognosis among older patients.Methods: In a retrospective study of OPSCCs diagnosed from 1995 to 2013 at 2 National Comprehensive Cancer Network-designated cancer centers, p16 immunohistochemistry and in situ hybridization (ISH) for HPV-16, high-risk DNA, and/or E6/E7 RNA were performed. The median age at diagnosis was compared by p16 and ISH tumor status. Trends in age were analyzed with nonparametric trends. Survival was analyzed with the Kaplan-Meier method and Cox proportional hazards models.Results: Among 239 patients, 144 (60%) were p16-positive. During 1998-2013, the median age increased among p16-positive patients (Ptrend = .01) but not among p16-negative patients (Ptrend = .71). The median age of p16-positive patients increased from 53 years (interquartile range [IQR] in 1995-2000, 45-65 years) to 58 years (IQR for 2001-2013, 53-64 years). Among patients ≥ 65 years old, the proportion of OPSCCs that were p16-positive increased from 41% during 1995-2000 to 75% during 2007-2013 (Ptrend = .04). Among all age groups, including older patients, a p16-positive tumor status conferred improved overall survival in comparison with a p16-negative status.Conclusions: The median age at diagnosis for HPV-related OPSCC is increasing as the proportion of OPSCCs caused by HPV rises among older adults. The favorable survival conferred by an HPV-positive tumor status persists in older adults. Cancer 2018;124:2993-9. © 2018 American Cancer Society. [ABSTRACT FROM AUTHOR]