Human Papillomavirus and the Epidemiology of Head and Neck Cancer

Epidemiology of Oral Human Papillomavirus Infection

Oral HPV infection is strongly associated with and the precursor to HPV-OPSCC. Oral HPV infection is detected in oral rinses that sample the oral cavity and the oropharynx. By convention in the literature, these infections are referred to as “oral” HPV infections, although both the oral cavity and the oropharynx are sampled. Oral HPV infection refers to viral DNA detected in oral rinses using polymerase chain reaction testing with PGMY primers and linear-array genotyping. Studies in the National Health and Nutrition Examination Survey (NHANES), which is representative of the U.S. civilian and noninstitutionalized population, provide the most robust prevalence estimates of oral HPV infection to date. Oral infection with HPV16, which is responsible for the overwhelming majority of HPV-OPSCCs, was observed in 1% of the U.S. population and was the most commonly detected type of oral HPV infection. Any oral HPV infection—including low-risk types, recognized to not have oncogenic potential, and high-risk types, which are carcinogenic—was more common. About 7% of individuals sampled (6.9% to 7.3%) had an oral HPV infection. This represents 14.2 million men and women in the United States with a prevalent oral HPV infection in 2011–2014. Prevalence estimates do vary by geographic location.

Oral HPV infection is at least twice as common in men as it is in women. Indeed, in NHANES, oral HPV prevalence was 11.5% (95% confidence interval [CI] 9.8% to 13.1%) among men compared with only 3.2% (95% CI 2.7% to 3.8%) among women. The prevalence of oral HPV infection is 61% higher among non-Hispanic blacks than among whites (PR, 1.61; 95% CI, 1.01 to 2.57). This is consistent with prior analyses, which found that black race is significantly associated with the presence of an oral HPV infection. Oral HPV infection has a unique age distribution that is bimodal, with an early peak in prevalence in the fourth decade and a second higher peak in the sixth to early seventh decade of life. Given the differential gender distribution, the bimodal nature of oral HPV infection is more pronounced among men. Reasons for these unique epidemiologic features of oral HPV infection are not well understood, but thought to relate to age-, gender- and race-associated differences in sexual behaviors.

As with most viruses, oral HPV infection is also strongly associated with immunosuppression. Human immunodeficiency virus (HIV), worsening CD4 count, and iatrogenically immunosuppressed patients (e.g., transplant recipients) are at increased risk for oral HPV infection.

The odds of oral HPV infection increase with increasing current tobacco use. This occurs in a dose-response fashion, such that the odds of oral HPV infection increase per measure of current tobacco exposure. Of note, the association between current tobacco use and oral HPV infection is stronger for women than for men. A dose-response relationship has also been observed between intensity of marijuana use and prevalence of oral HPV infection.

Given that oral HPV infection is a sexually transmitted infection, it is not unexpected that the presence of oral HPV infection is strongly associated with sexual behaviors. Oral HPV infection is associated with ever performing oral sex, ever having vaginal sex, ever having anal sex, increasing lifetime vaginal and oral sex partners, deep tongue kissing, early oral and vaginal sexual debut, and lack of condom use ( Table 74.1 ). Although each of these sexual behaviors has consistently been shown to be associated with the presence of oral HPV infection, they are also recognized to be colinear, and, therefore, the contribution of each behavior independently is unknown.

The natural history of oral HPV infection has not been comprehensively investigated to date. Initial data from large cohort studies suggest that most incident infections are cleared within 1 year, with a median duration of infection of about 7 months (6.9 months; 95% CI, 6.2 to 9.3). The natural history of oral HPV infection appears to differ from anogenital HPV infection, although further research is necessary. Factors associated with clearance and persistence of oral HPV include tobacco use, systemic immunosuppression (e.g., CD4 count), and differences in incidence secondary to frequency of exposure (e.g., sexual behaviors) (see Table 74.1 ). There are also significant gender differences in oral HPV infection acquisition and clearance that are not fully understood: Men have a higher risk of incident infection even when compared to women with similar numbers of sexual partners, and are less likely than women to clear infections.

Epidemiology of Human Papillomavirus-Positive Oropharyngeal Squamous Cell Cancers

Incidence

HPV-OPSCC accounts for 30% of OPSCCs worldwide, and 60% to 85% of OPSCCs in recent U.S. series. Although the incidence of HNSCC overall has declined in the United States, attributed to a successful tobacco-cessation campaign, the incidence of OPSCC has significantly risen in recent decades. This is driven by an increase of HPV-OPSCC, the incidence of which increased by 225% from 1988 to 2004 in an analysis of the U.S. Surveillance, Epidemiology and End Results (SEER) Program a cancer registry. The proportion of OPSCCs that are HPV positive also increased in the same calendar periods, from 16% in 1984–1989 to approximately 70% in 2000–2004 ( Fig. 74.1 ). The shift in epidemiologic trends is likely due to increased oral sexual activity attributed to the sexual revolution ; however, other unknown factors may also contribute to the increase in HPV-OPSCC. The incidence trends are largely among white men, and more recently Hispanic men. Projections from the SEER data predict that HPV-OPSCC will dramatically rise in the United States and that the incidence of HPV-OPSCC in men and women will be greater than cervical cancer in women. The incidence trends of HPV-OPSCC are similar in other economically developed countries and are especially notable in recent birth cohorts of men. The geographic differences in HPV-OPSCC appear to be driven by differences in sexual behaviors and tobacco consumption.