Study Shows That Men are More Vulnerable to Oral HPV Infection Than Women

The incidence of head and neck cancers, which is often correlated with patterns of tobacco use,¹ differs by geographic region. Although the incidence of head and neck cancer in general has been declining in many countries and regions in recent years, the incidence of oropharyngeal cancers, such as cancers of the base of tongue, tonsil, and other parts of the oropharynx, has significantly and rapidly increased over the past 20 years in the US.² Furthermore, the increasing incidence of oropharyngeal cancers has been attributed to human papillomavirus (HPV) infection rather than smoking, as smoking rates have been declining during this same period of time. Unfortunately, oropharyngeal cancers are on track to become the dominant HPV-associated cancer in the US, with the annual number of HPV-positive oropharynx cancers projected to overcome that of cervical cancers by the year 2020.³

HPV was implicated as the primary cause of the increased incidence of these cancers based on the prevalence of HPV DNA in tumors, as well as the rapidly increasing incidence of HPV-positive oropharyngeal cancers. The prevalence of HPV in oropharyngeal tumors increased from 16% during the late 1980s to 72% during the early 2000s in the US.³ However, oropharyngeal cancer incidence increased among men in the US at the same time that rates significantly declined among women.²

The underlying causes of the observed gender differences in oropharyngeal cancer incidence in the US remain unknown. A team led by Gypsyamber D’Souza, PhD, MPH, an associate professor of epidemiology at the Johns Hopkins Bloomberg School of Public Health in Baltimore MD, conducted a study in order to address this research question. In explaining their study, D’Souza et al stated, "We investigated differences in oral HPV natural history among young adult men and women, a population known to be at high risk for sexually transmitted infections." The results from their study were recently published in the Journal of Infectious Diseases.⁴

D’Souza and colleagues conducted a prospective, natural history study of oral HPV infection among adult men and women aged 18—25 years enrolled in the Study of Papillomavirus in Teens and Twenties between April 2010 and November 2012.⁵ Study participants were followed every three months for 18 months, and those with persistent infection at 18 months had their follow-ups extended up to 30 months. A 30-second oral rinse and gargle sample was collected at each visit. Additionally, study participants completed a computer assisted self-interview in order to provide behavioral information, predominantly focused on sexual behaviors. The median follow-up was 18 months, with a median of six oral rinse samples collected per participant. These samples were processed and tested for 36 HPV genotypes using PCR.

The majority of the baseline demographic variables that were assessed did not differ between the genders, and the sexual behavior data indicated that both genders reported nearly identical percentages (~70%) for recent oral sex on an individual of the opposite sex.

As expected, men showed a higher oral HPV prevalence and incidence when compared with women. Furthermore, significant interactions were detected between gender, oral sexual behavior, and risk of incident oral HPV infection. More specifically, the risk of oral HPV infection significantly increased among men who recently engaged in oral sex, but not among women.

Regarding the effect of gender on oral HPV clearance, additional study data showed that the median time to clearance was significantly longer in men, and that men remained 37% less likely than women to clear an oral HPV infection.

In the discussion of their study and its results, D’Souza and colleagues stated, "We describe, for the first time, a difference in this oral HPV natural history between men and women." The study data very clearly, and perhaps surprisingly, demonstrated that men were at a much higher risk for oral HPV infection when performing oral sex on an individual of the opposite sex, and that HPV clearance in men was far less robust than in women.” Dr. D’Souza and her team related HVP infection back to oropharyngeal cancer by stating, "These natural history differences suggest that increased oral HPV16 prevalence and higher rates of HPV-related oropharyngeal cancer observed in men compared to women in the US are explained both by higher oral HPV acquisition rates, as well as slower clearance once infected."

Based on the results of this study, it would seem that men in the US are much more vulnerable to HPV infection from performing oral sex on opposite sex partners than women, and have a great deal more difficultly in oral HPV clearance. These gender-based differences may explain the skyrocketing incidence of oropharyngeal cancers in men as opposed to women in the US.

William Perlman, PhD, CMPP is a former research scientist currently working as a medical/scientific content development specialist. He earned his BA in Psychology from Johns Hopkins University, his PhD in Neuroscience at UCLA, and completed three years of

postdoctoral fellowship in the Neuropathology Section of the Clinical Brain Disorders Branch of the National Institute of Mental Health.

References

1. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2011;127:2893—917.
2. Chaturvedi AK, Engels EA, Anderson WF, Gillison ML. Incidence trends for human papillomavirus-related and -unrelated oral squamous cell carcinomas in the United States. J Clin Oncol 2008;26:612—9.
3. Chaturvedi A, Engels E, Pfeiffer R, Hernandez B, Xiao W, Kim E, et al. Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol 2011;29:4294—301.
4. D'Souza G, Wentz A, Kluz N, Zhang Y, Sugar E, Youngfellow RM, Guo Y, Xiao W, Gillison ML. Gender differences in risk factors and natural history of oral human papillomavirus (HPV) infection. J Infect Dis. 2016 Feb 10. pii: jiw063. [Epub ahead of print]
5. D'Souza G, Kluz N, Wentz A, et al. Oral Human Papillomavirus (HPV) Infection among Unvaccinated High-Risk Young Adults. Cancers 2014; 6:1691-704.