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

Cancer. 2021 Apr 1;127(7):1029-1038. doi: 10.1002/cncr.33346. Epub 2021 Jan 11.


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.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Age Distribution
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Case-Control Studies
  • Extramarital Relations
  • Female
  • Human papillomavirus 16 / immunology
  • Humans
  • Logistic Models
  • Male
  • Middle Aged
  • Odds Ratio
  • Oncogene Proteins, Viral / analysis
  • Oropharyngeal Neoplasms / epidemiology
  • Oropharyngeal Neoplasms / virology*
  • Papillomavirus Infections / complications*
  • Repressor Proteins / analysis
  • Risk
  • Risk Factors
  • Sexual Behavior* / statistics & numerical data
  • Sexual Partners*
  • Smoking / adverse effects
  • Socioeconomic Factors
  • Time Factors
  • United States / epidemiology
  • Unsafe Sex
  • Young Adult


  • E6 protein, Human papillomavirus type 16
  • Oncogene Proteins, Viral
  • Repressor Proteins