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Cancers Head Neck. 2018 Jun 20;3:4. doi: 10.1186/s41199-018-0031-y. eCollection 2018.

Sex differences in patients with high risk HPV-associated and HPV negative oropharyngeal and oral cavity squamous cell carcinomas.

Li H1, Park HS1,2,3, Osborn HA1,4,3, Judson BL1,4,3.

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1Yale School of Medicine, New Haven, CT USA.
2Department of Therapeutic Radiology, Yale New Haven Hospital, New Haven, CT USA.
4Yale Cancer Center, 330 Cedar Street, PO Box 208062, New Haven, CT 06520-8062 USA.
3Department of Surgery (Section of Otolaryngology), Yale New Haven Hospital, New Haven, CT USA.



Human papilloma virus (HPV)-associated head and neck cancer is now recognized as a distinct clinical entity from HPV-negative tumors, which are primarily associated with tobacco and alcohol exposure.Little is known, however, about the behavior of HPV-associated oropharynx (OP) and oral cavity (OC) SCCs as two distinct cancers and how sex affects the overall survival (OS) in these two cancers. The objective of our study is to determine if sex is associated with overall survival (OS) in patients with high-risk human papillomavirus (HPV)-positive and HPV-negative squamous cell carcinomas (SCC) in the oropharynx and oral cavity sites.


This is a retrospective cohort study using a national database. Data were extracted from the National Cancer Database (NCDB) of patients diagnosed with OP or OC SCC from 2010 to 2014. Univariate and multivariate survival analyses were conducted with chi-square tests, Kaplan-Meier estimates, log-rank tests, and Cox proportional hazards multivariable modeling.


A total of 30,707 patients (13,694 OP HPV-associated, 7933 OP HPV-, 1220 OC HPV-associated, 7860 OC HPV-) were identified. In all four groups, women tended to be older and have lower T and N clinical classification than men. Though there were no significant differences in OS between the sexes in OP HPV-associated cancers, female sex was associated with worse OS in OP HPV- cancers (HR: 1.15; 95% CI 1.04-1.28, p = 0.004), whereas it was associated with improved OS in OC HPV-associated and HPV- cancers (HPV-associated: HR: 0.71; 95% CI 0.50-0.99, p = 0.048; HPV-: HR: 0.87; 95% CI 0.78-0.95, p = 0.004).


The effect of sex on OS in OC and OP SCC appears to vary based on tumor location and HPV status. While the source of this difference in prognostic association is unclear, it may be related to an emerging difference in the biology of HPV carcinogenesis in these locations.


Head and neck cancer; Human papilloma virus; Oral cavity cancer; Oropharyngeal cancer; Sex difference

Conflict of interest statement

Our study is exempt from review by the Yale Human Research Protection Program because it uses a pre-existing, de-identified public database.Not applicable.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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