Human Papillomavirus-Associated Head and Neck Cancer

Juan C. Nogues, BS; Scott Fassas, MD; Collin Mulcahy, MD; Philip E. Zapanta, MD


J Am Board Fam Med. 2021;34(4):832-837. 

In This Article


The majority of HPV-positive OPSCCs are caused by HPV 16 with minor contributions from 18, 31, and 33. In 2006, the first HPV vaccine, Gardasil 4, was approved for prevention of cervical cancer and covered HPV 6, 11, 16, and 18. The latest vaccine, Gardasil 9, covers HPV strains 6, 11, 16, 18, 31, 33, 45, 52, and 58 and therefore protects against the most carcinogenic strains of HPV. It has gained US Food and Drug Administration (FDA) approval for prevention of cervical, vulvar, vaginal, anal, oropharyngeal, and other head and neck cancers[16] and is administered in either 2 or 3 doses depending on the age of the patient at the time of the first dose (Table 2). The primary target group for the vaccine is children over the age of 9, ideally before the onset of sexual activity; however, Gardasil 9 has been FDA approved for both men and women up to the age of 45.[17] Despite this expanded coverage, the CDC does not currently recommend routine HPV vaccination for patients above the age of 26 but rather shared clinical decision-making on a case-by-case basis.[18,19] Because of this, insurance may not always cover the vaccine in this extended age group.

Despite the wide availability of HPV vaccines in the United States, many providers are unaware of the link between HPV and OPSCC. A 2017 study reported that only 16% of pediatricians were aware of the link between OPSCC and HPV, and only 46% had knowledge that HPV-related oropharyngeal cancer incidence was increasing in the United States.[20] What is more alarming is that a 2019 national vaccination study found that among adolescents between 13 and 17 years old, only 54% were up to date with the recommended HPV vaccination series.[21] Males (52%) were shown to have a slightly lower vaccination rate than females (57%).

The lack of awareness and low vaccination rate highlights the paramount role that PCPs play in disease prevention. While the vaccine is targeted for virginal adolescents, a recent study of men between the ages of 27 and 45 found that the immune response in this population was comparable to that of younger men ages 16 to 26.[22] Armed with this information, PCPs can increase HPV vaccination rates and greatly reduce the morbidity and mortality associated with OPSCC.

In addition, oro-genital sex is the most important risk factor for developing HPV-positive OPSCC. While studies have shown that properly utilized barrier methods of protection (condoms and dental dams) can lower the risk of contracting HPV,[23] in practice, they have poor adoption and user compliance for oral sex, especially among young adults.[24] Thus, although it is prudent to suggest barrier use for patients who are receptive, it should not serve as an alternative to vaccination, especially for high-risk individuals with multiple sexual partners.

Lastly, smoking is a well-known risk factor for HPV-negative OPSCC but may also be associated with increased risk of HPV-positive OPSCC. A recent study demonstrated that smoking prolongs HPV infections in the oral cavity,[25] suggesting it could play a role in the pathogenesis of HPV-related OPSCC. This provides more evidence to support smoking cessation for patients, especially those at high risk or who have not been vaccinated.