HPV prophylactic vaccines and the potential prevention of noncervical cancers in both men and women

Abstract

Human papillomavirus (HPV) is a necessary cause of cervical cancer. In addition, on the basis of the fulfillment of a combination of viral as well as epidemiological criteria, it is currently accepted that a proportion of anal, oropharyngeal, vulvar, and vaginal cancers among women and anal, oropharyngeal, and penile cancers among men are etiologically related to HPV. At these noncervical sites with etiologic heterogeneity, HPV-associated cancers represent a distinct clinicopathological entity, which is generally characterized by a younger age at onset, basaloid or warty histopathology, association with sexual behavior, and better prognosis, when compared with their HPV-negative counterparts. Currently available estimates indicate that the number of HPV-associated noncervical cancers diagnosed annually in the US roughly approximates the number of cervical cancers, with an equal number of noncervical cancers among men and women. Furthermore, whereas the incidence of cervical cancers has been decreasing over time, the incidence of anal and oropharyngeal cancers, for which there are no effective or widely used screening programs, has been increasing in the US. The efficacy of HPV vaccines in preventing infection at sites other than the cervix, vagina, and vulva should, therefore, be assessed (eg, oral and anal). Given that a substantial proportion of cervical cancers (approximately 70%) and an even greater proportion of HPV-associated noncervical cancers (approximately 86% to 95%) are caused by HPV16 and 18 (HPV types that are targeted by the currently available vaccines), current HPV vaccines may hold great promise (provided equivalent efficacy at all relevant anatomic sites) in reducing the burden of HPV-associated noncervical cancers, in addition to cervical cancers.

FIGURE 1

Incidence trends for HPV-associated cancers in the US, 1973–2004 are depicted. Incidence rates for HPV-associated cancers in the US were derived from 9 population-based cancer registries covered by the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER 9) program during 1973–2004. These registries cover approximately 9% of the US population. Anatomic site classifications are identical to those used in the ABHACUS monograph as described in Watson et al. Table 2, with the exception of rectal cancers, which were not included in this analysis. Incidence rates are shown for cancers of the cervix (ICD-O-3 topography codes: C530-539; all histologies), anus (ICD-O-3 topography codes: C210-218; restricted to squamous cell histologies: ICD-O-3 codes: 8050-8084 and 8120-8131), oropharynx (restricted to sites believed to be HPV-associated with ICD-O-3 codes: C019, C024, C028, C090-099, C102, C108, C109, C140, C142, and C148; restricted to squamous cell histologies: ICD-O-3 codes: 8050-8084 and 8120-8131), penis (ICD-O-3 topography codes: C600-609; restricted to squamous cell histologies: ICD-O-3 codes: 8050-8084 and 8120-8131), vagina (ICD-O-3 codes: C529; restricted to squamous cell histologies: ICD-O-3 codes: 8050-8084 and 8120-8131), and vulva (ICD-O-3 codes: C510-519; restricted to squamous cell histologies: ICD-O-3 codes: 8050-8084 and 8120-8131). Rates are age-adjusted to the US 2000 population. APC denotes the annual percentage change in incidence; APC was calculated in log-linear models by regressing the calendar year of diagnosis on the log of the age-adjusted rate by using SEER*Stat. The P-value for the annual percentage change in incidence rates during 1973 to 2004 is also shown in each panel.

FIGURE 2

(A) Estimated annual number of HPV-associated cancers in the US, 1998–2003, are shown in this panel. Numbers are based on worldwide estimates of the proportion of HPV-associated cancers. (B) Estimated annual number of HPV-associated cancers in the US, 1998–2003, are shown. Numbers are based on US-specific estimates of the proportion of HPV-associated cancers. The estimated annual number of HPV-associated cancers in the US during 1998–2003 are based on data presented in Watson et al. The Watson data are from 39 population-based cancer registries that participate in the National Program of Cancer Registries (NPCR) and/or the Surveillance, Epidemiology, and End Results (SEER) Program and meet high-quality data criteria. These registries cover approximately 83% of the US population. The values from which Figure 2 is derived are shown in Table 4. The total number of cases for each cancer is partitioned into the number of cases caused by HPV genotypes 16 and 18 (in grey), which are, therefore, potentially preventable by the currently available HPV vaccine, and the number of cases caused by other HPV genotypes are shown in black.

FIGURE 3

(A) Estimated annual number of HPV-associated cancers in the US by gender, 1998–2003, is depicted. Numbers are based on worldwide estimates of the proportion of HPV-associated cancers. (B) Estimated annual number of HPV-associated cancers in the US by gender, 1998–2003, is depicted. Numbers are based on US-specific estimates of the proportion of each cancer that is attributable to HPV infection. These numbers are based on data presented in Watson et al. The Watson data are from 39 population-based cancer registries that participate in the National Program of Cancer Registries (NPCR) and/or the Surveillance, Epidemiology, and End Results (SEER) Program and meet high-quality data criteria. These registries cover approximately 83% of the US population. The values from which Figure 3 is derived are shown in Table 4. Results are shown for cervical cancer, other HPV-associated cancers among women, and HPV-associated cancers among men. The annual number of each component cancer is also shown for non-cervical HPV-associated cancers among women and for HPV-associated cancers among men.