US Assessment of HPV Types in Cancers: Implications for Current and 9-Valent HPV Vaccines

Mona Saraiya; Elizabeth R. Unger; Trevor D. Thompson; Charles F. Lynch; Brenda Y. Hernandez; Christopher W. Lyu; Martin Steinau; Meg Watson; Edward J. Wilkinson; Claudia Hopenhayn; Glenn Copeland; Wendy Cozen; Edward S. Peters; Youjie Huang; Maria Sibug Saber; Sean Altekruse; Marc T. Goodman


J Natl Cancer Inst. 2015;107(6) 

In This Article

Abstract and Introduction


Background: This study sought to determine the prevaccine type-specific prevalence of human papillomavirus (HPV)–associated cancers in the United States to evaluate the potential impact of the HPV types in the current and newly approved 9-valent HPV vaccines.

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Methods: The Centers for Disease Control and Prevention partnered with seven US population-based cancer registries to obtain archival tissue for cancers diagnosed from 1993 to 2005. HPV testing was performed on 2670 case patients that were fairly representative of all participating cancer registry cases by age and sex. Demographic and clinical data were evaluated by anatomic site and HPV status. Current US cancer registry data and the detection of HPV types were used to estimate the number of cancers potentially preventable through vaccination.

Results: HPV DNA was detected in 90.6% of cervical, 91.1% of anal, 75.0% of vaginal, 70.1% of oropharyngeal, 68.8% of vulvar, 63.3% of penile, 32.0% of oral cavity, and 20.9% of laryngeal cancers, as well as in 98.8% of cervical cancer in situ (CCIS). A vaccine targeting HPV 16/18 potentially prevents the majority of invasive cervical (66.2%), anal (79.4%), oropharyngeal (60.2%), and vaginal (55.1%) cancers, as well as many penile (47.9%), vulvar (48.6%) cancers: 24 858 cases annually. The 9-valent vaccine also targeting HPV 31/33/45/52/58 may prevent an additional 4.2% to 18.3% of cancers: 3944 cases annually. For most cancers, younger age at diagnosis was associated with higher HPV 16/18 prevalence. With the exception of oropharyngeal cancers and CCIS, HPV 16/18 prevalence was similar across racial/ethnic groups.

Conclusions: In the United States, current vaccines will reduce most HPV-associated cancers; a smaller additional reduction would be contributed by the new 9-valent vaccine.


Human papillomavirus (HPV) infection is causally associated with most anogenital[1] cancers, as well as oropharyngeal (OP) and possibly oral cavity (OC) and laryngeal cancers, contributing to an estimated 600 000 incident cancers worldwide and 250 000 premature deaths.[2,3] A small subset of all HPV types are considered oncogenic.[4,5] Internationally, the etiologic fraction of HPV-associated malignancy, based on HPV detection, varies by geography and anatomic site, but overall suggests that 70% of cervical cancers are caused by HPV 16/18, and HPV 16 is the primary oncogenic virus in other anogenital and OP cancers. The fraction of HPV detected in OP cancers ranges from 13% to 72%, with the highest in North America.[2,6,7] HPV detection varies from 40% in vaginal to 90% in anal cancers.[2]

Widespread uptake of HPV 16/18 vaccines has already been shown to decrease high-grade cervical lesions[8,9] and is anticipated to substantially reduce the burden of HPV-associated cancers. Clinical trials and ad hoc analyses demonstrated high efficacy of HPV 16/18 vaccines in preventing cervical, vulvar, anal, and vaginal precursor lesions.[10–13] A recent secondary analysis supports efficacy of the 16/18 vaccine in preventing oral HPV 16/18 infection.[14] The US Food and Drug Administration (FDA) recently approved the nonavalent (9-valent) vaccine targeting HPV 6/11/16/18 and five additional oncogenic types,[15] which could extend protection to almost 90% of all cervical cancers worldwide.[16,17] However, reductions in cancer incidence will take several decades to achieve given the long natural history of disease progression and low vaccine coverage in the United States.[18]

Baseline and ongoing surveillance of type-specific, population-based HPV prevalence in cervical and other HPV-associated cancers will strengthen measures of the impact of HPV vaccines on cancer. Presently, these systematic surveillance efforts have not been established in the United States. Indeed, the United States has been underrepresented in international studies of HPV prevalence in tumors.[19] To address this gap, the CDC used population-based cancer registries to establish the type distribution in HPV-associated malignancies prior to the public introduction of the HPV vaccine in 2006. Cancer registries provide well-annotated tissues linked to demographic and clinical data that allow determination of type-specific differences in HPV prevalence that may be important for monitoring impact and cost-effective analyses for current and future vaccines.