Timing, number, and type of sexual partners associated with risk of oropharyngeal cancer

Abstract

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.

Keywords: head and neck cancer; oropharyngeal neoplasms; papillomaviridae; risk factors; sexual behavior.

Figure 1:

Black squares represent unadjusted odds ratios of HPV-OPC for case subjects versus controls. Vertical lines represent 95% confidence intervals. Red asterisks represent statistical significance. Odds ratios and 95% confidence intervals were derived from conditional logistic regression analysis for case-control comparison. A: Odds of HPV-OPC if a participant reported performing oral sex at sexual debut. B: Dose-response relationship for age of first oral sex encounter. C: Dose-response relationship of number for people performed oral sex on in lifetime. D: Dose-response relationship for oral sex-years, a measure of intensity of oral sexual partners defined as number of partners performed oral sex on per ten years since sexual debut.

Figure 2:

Black squares represent unadjusted odds ratios of HPV-OPC for case subjects versus controls. Vertical lines represent 95% confidence intervals. Red asterisks represent statistical significance. Odds ratios and 95% confidence intervals were derived from conditional logistic regression analysis for case-control comparison. A: Dose-response relationship of number of casual sex partners and risk of HPV-OPC. B: Odds of HPV-OPC by presence or suspicion of extramarital sex C: Odds of HPV-OPC when a participant reported having a sexual partner greater than 10 years older when they were under 23 years old