Surprisingly, in the United States, the most common cancer associated with human papillomavirus (HPV) is oropharyngeal squamous cell cancer (SCC), with one study reporting 15,479 cases among men and 3,428 cases among women in 2015.1 In the same year, the investigators reported 11,788 cases of cervical cancer.1 A public health concern is that cases of oropharyngeal SCC are increasing, while cases of cervical cancer are decreasing. From 1999 to 2015, the rate of oropharyngeal SCC increased annually among both men and women, at rates of 2.7% and 0.8% per year, respectively. By contrast, the rate of cervical cancer decreased by 1.6% per year.1
Although the incidence of HPV-negative oropharyngeal SCC (cases associated with cigarette smoking) has declined by 50% from 1988 to 2004, the incidence of HPV-positive oropharyngeal SCC has increased by 225%, with much of the increase occurring among young, white men.2 HPV infection is a major cause of oropharyngeal SCC at the base of the tongue and tonsils, but not in the soft palate or oropharyngeal walls.3
Most physicians and parents recognize that the 9-valent (9v)HPV vaccine prevents the majority of cervical cancers and precancers in women. Far fewer people realize that there is an important opportunity to prevent a large number of oropharyngeal cancers by improving 9vHPV vaccination in men and women.
Which HPV types are associated with oropharyngeal cancer?
HPV16 is the most common HPV type associated with oropharyngeal SCC. Among these cancer types, greater than 80% harbor HPV16, with greater than 90% harboring HPV16 or 18 and less than 10% of tumors associated with HPV types 31, 33, 45, 52, or 58.4-7
The high prevalence of HPV16 in patients with oropharyngeal cancer raises the question of the HPV status of the intimate partner of the index patient. In one study of 164 people with HPV detected in their oropharyngeal, the partner of the index patient had a low prevalence of high-risk HPV types (1.2%) in oral rinse and gargle samples, similar to the rate in the general population (1.3%).7 This finding is reassuring and suggests that intimate partners of patients with HPV-positive oropharyngeal cancer effectively clear high-risk HPV virus from the oropharynx. The HPV status of the genital tissue of the intimate partner of an index patient with oropharyngeal SCC has not been adequately studied.
Men are more likely than women to harbor oral HPV
Among a sample of 5,501 men and women aged 14 to 69 years from the National Health and Nutrition Examination Survey, oral rinses were obtained and analyzed for the presence of HPV.8 The prevalence of any oral HPV and any oral high-risk HPV was 6.9% and 3.7%, respectively. Oral HPV-16 was detected in 1.6% of men and 0.3% of women. The prevalence of HPV was higher among current smokers, heavy alcohol drinkers, and people with a history of a greater number of sexual partners. In men and women reporting more than 20 lifetime sexual partners, the prevalence of oral HPV was 20%.
In a study of 2,627 men and women aged 18 to 33 years, the prevalence of oral HPV 16/18/6/11 was lower among those vaccinated versus those unvaccinated (0.11% and 1.6%, respectively; P = .008).9 Among men, oral HPV 16/18/6/11 was lower among those vaccinated versus unvaccinated (0.0% and 2.13%, respectively; P = .007).9 The results of this observational study support the important role of vaccination in reducing oral HPV infection.
9vHPV vaccine: Indications and immunization schedule
In 2020, the US Food and Drug Administration (FDA) approved the 9-valent human papillomavirus (9vHPV) vaccine for the prevention of oropharyngeal cancer. The 9vHPV vaccine contains inactive L1 capsid proteins for 9 HPV types, including types 6, 11, 16, 18, 31, 33, 45, 52, and 58. The vaccine stimulates the production of neutralizing antibodies to the capsid protein.
9vHPV is approved for females aged 9 to 45 years to prevent cancers and precancers of the cervix, vulva, vagina, and anus caused by HPV types 16, 18, 31, 33, 45, 52, and 58.1 It is also approved for males aged 9 to 45 years to prevent cancer and precancers of the anus caused by those viral types. In 2020 the 9vHPV vaccine was approved by the FDA to prevent oropharyngeal cancer in males and females. Of note, the FDA reported that, “the oropharyngeal and head and neck cancer indication is approved under accelerated approval based on effectiveness in preventing HPV-related anogenital disease. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.”2
The Advisory Committee on Immunization Practices (ACIP) recommends routine vaccination of girls and boys, 11 to 12 years of age.1 Children with a history of sexual abuse or assault can start the vaccine at 9 years of age. Catch-up vaccination is recommended for all females and males through age 26 years. The ACIP recommends shared clinical decision-making regarding vaccination for some adults 27 to 45 years of age. Gynecologists with routine exposure to HPV may have occupational risk that warrants HPV vaccination3 (see “As a gynecologist, should you receive the 9vHPV vaccine?”).
For most individuals who start the vaccine series before age 15, two doses of 9vHPV vaccine are recommended, with the second dose 6 to 12 months following the first dose. For teens and adults aged 15 to 26 years, 3 doses of 9vHPV vaccine are recommended, with the second dose 1 to 2 months later and the third dose 6 months following the first dose. Immunocompromised individuals 9 to 26 years of age, including those with HIV infection, should receive 3 doses of the vaccine.
References
1. Meites E, Szilagyi PG, Chesson HW, et al. Human papillomavirus vaccination for adults: updated recommendations of the Advisory Committee on Immunization Practices. MMWR Morb Mortal Wkly Rep. 2019;68:698-702.
2. Gardasil 9 [package insert]. Whitehouse Station, NJ: Merck & Co. Inc; 2020.
3. Stockdale CK, Einstein MH, Huh WK. ASCCP recommends HPV vaccination for providers. February 19, 2020. https://www.asccp.org/Assets/d3abdb05-25c5-4e58-9cec-05c11fb2b920/637177876310030000/hpv-vaccinemember-announcment-02-19-20-pdf. Accessed October 23, 2020.
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