Human Papillomavirus–Associated Cancers — United States, 2008–2012
Weekly / July 8, 2016 / 65(26);661–666
Laura J. Viens, MD1; S. Jane Henley, MSPH1; Meg Watson, MPH1; Lauri E. Markowitz, MD2; Cheryll C. Thomas, MSPH1; Trevor D. Thompson1; Hilda Razzaghi, PhD1; Mona Saraiya, MD1 (View author affiliations)View suggested citation
What is already known about this topic?
Persistent infections with human papillomavirus (HPV) can cause carcinomas of the cervix, and squamous cell cancers of the vulva, vagina, penis, anus, rectum, and oropharynx. Many of these cancers are preventable with currently available vaccines; effective screening programs can identify cervical precancers for treatment before they can progress to cancer.
What is added by this report?
An average of 38,793 HPV-associated cancers (11.7 per 100,000 persons) were diagnosed annually in the United States during 2008–2012, including 23,000 (13.5) among females and 15,793 (9.7) among males. Among these cancers, CDC estimates that 30,700 (79%) can be attributed to HPV, and 28,500 of these are attributable to HPV types that are preventable with the 9-valent HPV vaccine.
What are the implications for public health practice?
Full vaccination coverage of the U.S. population could prevent future HPV-attributable cancers and potentially reduce racial and ethnic disparities in HPV-associated cancer incidence. Ongoing surveillance for HPV-associated cancers using high-quality population-based registries is needed to monitor trends in cancer incidence that might result from increasing use of HPV vaccines and changes in cervical cancer screening practices.
Human papillomavirus (HPV) is a known cause of cervical cancers, as well as some vulvar, vaginal, penile, oropharyngeal, anal, and rectal cancers (1,2). Although most HPV infections are asymptomatic and clear spontaneously, persistent infections with one of 13 oncogenic HPV types can progress to precancer or cancer. To assess the incidence of HPV-associated cancers, CDC analyzed 2008–2012 high-quality data from the CDC’s National Program of Cancer Registries and the National Cancer Institute’s Surveillance, Epidemiology, and End Results program. During 2008–2012, an average of 38,793 HPV-associated cancers were diagnosed annually, including 23,000 (59%) among females and 15,793 (41%) among males. By multiplying these counts by the percentages attributable to HPV (3), CDC estimated that approximately 30,700 new cancers were attributable to HPV, including 19,200 among females and 11,600 among males. Cervical precancers can be detected through screening, and treatment can prevent progression to cancer; HPV vaccination can prevent infection with HPV types that cause cancer at cervical and other sites (3). Vaccines are available for HPV types 16 and 18, which cause 63% of all HPV-associated cancers in the United States, and for HPV types 31, 33, 45, 52, and 58, which cause an additional 10% (3). Among the oncogenic HPV types, HPV 16 is the most likely to both persist and to progress to cancer (3). The impact of these primary and secondary prevention interventions can be monitored using surveillance data from population-based cancer registries.
CDC analyzed data from population-based cancer registries that participate in the CDC’s National Program of Cancer Registries and the National Cancer Institute’s Surveillance, Epidemiology, and End Results program and met the criteria for high data quality for all years 2008–2012, covering approximately 99% of the U.S. population.* Cases were classified by anatomic site using the International Classification of Diseases for Oncology, 3rd Edition† and were confirmed histologically. HPV-associated cancers were defined as invasive cancers at anatomic sites (i.e., cervix, vulva, vagina, penis, oropharynx, anus, and rectum) with cell types in which HPV DNA frequently is found (all carcinomas of the cervix, including adenocarcinomas and squamous cell cancers [SCC]; SCCs only for the other anatomic sites). Oropharyngeal cancers included cancers of the base of tongue; pharyngeal tonsils, anterior and posterior tonsillar pillars, and glossotonsillar sulci; anterior surface of soft palate and uvula; and lateral and posterior pharyngeal walls.§ Age-adjusted incidence rates were calculated per 100,000 persons and standardized to the 2000 U.S. standard population. Rates were considered significantly different from the referent category at a p-value of <0.05.
Cancer registries do not routinely collect information on HPV DNA presence in cancer tissues, and HPV-associated cancers defined by anatomic site and cell type include cancers not caused by HPV. Therefore, to calculate HPV-attributable cases, the number of HPV-associated cancers was multiplied by the percentage of each cancer type attributable to HPV based on polymerase chain reaction genotyping studies (3). Because rectal squamous cell carcinoma was not included in the genotyping study, the HPV-attributable percentage for anal squamous cell carcinoma, a biologically similar tumor, was used (2).
Overall, an average of 38,793 HPV-associated cancers (11.7 per 100,000 persons) were diagnosed annually, including 23,000 (13.5) among females and 15,793 (9.7) among males. The most common of these cancers were 11,771 (7.4 per 100,000 females) cervical carcinomas, and 15,738 (4.5 per 100,000 persons) oropharyngeal SCCs (12,638 among males and 3,100 among females) (Table 1). Rates of oropharyngeal SCC were higher among males (7.6) than females (1.7), whereas rates of anal and rectal SCC were higher among females (1.8 and 0.3) than males (1.1 and 0.2).
Rates of cervical carcinoma were higher among blacks (9.2) than among whites (7.1), and among Hispanics (9.7) than non-Hispanics (7.1); a similar pattern was observed for penile SCCs (Table 1). Rates of vulvar SCC were lower among blacks (1.5) compared with whites (2.1) and among Hispanics (1.3) compared with non-Hispanics (2.1). Among females, rates of anal SCC were lower among blacks (1.4) than whites (1.9), but among males, were higher among blacks (1.5) compared with whites (1.1). The rate of anal SCC among Hispanic males and females (1.1) was lower than among non-Hispanics (1.5). Rates of oropharyngeal SCC in both males and females were higher among whites (8.0 and 1.8) compared with blacks (6.9 and 1.5), and among non-Hispanics (8.0 and 1.8) compared with Hispanics (4.2 and 0.9).
By state, overall rates of all HPV-associated cancers combined ranged from 7.5 per 100,000 persons (Utah) to 14.7 (Kentucky); among females, rates ranged from 9.1 (Utah) to 17.0 (Kentucky and West Virginia), and among males, rates ranged from 6.0 (Utah) to 12.8 (District of Columbia) (Table 2). Most states with overall HPV-associated cancer rates that exceeded the U.S. rate (11.7 per 100,000) were located in the U.S. Census Southern region,¶ driven by a similar pattern in the distribution of the rates of cervical, anal, and oropharyngeal cancers. The highest rate of cervical cancer was found in Puerto Rico (11.7 per 100,000 females); among the states, the lowest was found in Vermont (4.1) and the highest in West Virginia (9.9).
By multiplying HPV-associated cancer counts by the percent attributable to HPV, 30,700 HPV-associated cancers (79%) were estimated to be attributable to HPV (Table 3). Among these, 24,600 (80%) were attributable to HPV types 16 and 18, which can be prevented by the bivalent, quadrivalent and 9-valent HPV vaccines, and 3,800 (12%) were attributable to the five additional HPV types (31, 33, 45, 52, 58), which can be prevented by the 9-valent HPV vaccine. Among cervical carcinoma cases, 7,800 cases were attributable to HPV types 16 and 18 and 1,700 were attributable to the additional HPV types. Among oropharyngeal SCC cases, 9,500 cases were attributable to HPV types 16 and 18, and another 900 cases were attributable to the additional types.
Each year during 2008–2012, an average of 38,793 HPV-associated cancers were diagnosed, including 23,000 among females and 15,793 among males; 79% of these were attributable to HPV. Compared with a previous analysis, which reported 33,369 HPV-associated cancer cases diagnosed each year during 2004–2008, the results of this analysis demonstrate an overall increase in HPV-associated cancer incidence, from 10.8 per 100,000 persons during 2004–2008 to 11.7 per 100,000 persons during 2008–2012, despite a slight decrease in the rate of cervical carcinoma (4). Part of this increase is because of the inclusion of additional subsites for oropharyngeal cancer; however, the increase persisted when these subsites were excluded from analysis.
The Advisory Committee on Immunization Practices recommends routine vaccination with any of the available HPV vaccines (bivalent, quadrivalent, or 9-valent) for females and quadrivalent or 9-valent for males (5). Vaccination is recommended at ages 11–12 years and through age 26 years for females and age 21 years for males, if they were not previously vaccinated (5). High-income countries have observed a population-level impact of HPV vaccination programs, including reductions in vaccine type prevalence and rates of anogenital warts, most of which are caused by HPV types 6 and 11, two types targeted by the quadrivalent and 9-valent HPV vaccines (6). Among U.S. adolescent females aged 13–17 years in 2014, 60.0% received >1 dose, 50.3% received >2 doses, and 39.7% received >3 doses; male coverage with >1, >2, and >3 doses was 41.7%, 31.4%, and 21.6%, respectively (7). Series initiation was higher among blacks and Hispanics compared with whites, and among persons below the poverty level, in both male and female U.S. populations. Increasing vaccination coverage could decrease the cancer incidence and disparities in the United States.
Most cervical cancers are preventable with regular screening for precancerous lesions among women aged 21–65 years linked with follow-up for abnormal test results (8); there are currently no effective population-based screening strategies for the other HPV-associated cancers. The Healthy People 2020 target for cervical cancer screening is 93%**; however in 2013, only 80.7% of women reported up-to-date cervical cancer screening, with even lower rates noted among Asians, Hispanics, women aged 51–65 years, foreign-born, uninsured, and publicly insured women (9).
The findings in this report are subject to at least two limitations. First, although population-based cancer registries provide a reliable system for counting invasive cancers, no registry routinely collects or reports information on HPV DNA status in cancer tissue, so the HPV-attributable cancers are only estimates. Second, reporting of race and ethnicity uses data from medical records, which might be inaccurate in a small proportion of cases.
Of the 38,793 cancers that occurred each year in the United States at anatomic sites associated with HPV, approximately 30,700 can be attributed to HPV. Of these, 24,600 cancers are attributable to HPV types 16 and 18, which are included in all current HPV vaccines, and 28,500 are attributable to high-risk HPV types included in the 9-valent HPV vaccine. Ongoing surveillance for HPV-associated cancers using high-quality population-based registries is needed to monitor trends in cancer incidence that might result from increasing use of HPV vaccines and changes in cervical cancer screening practices.
Corresponding author: Laura J. Viens, email@example.com, 404-639-3286.
1 Division of Cancer Prevention and Control, National Center for Chronic Disease Prevention and Health Promotion, CDC; 2 Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, CDC.
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§ American Joint Committee on Cancer (AJCC). AJCC Cancer Staging Manual. 7th ed. Chicago, IL: Springer; 2010.
TABLE 1. Rate* and average annual number of human papillomavirus (HPV)-associated cancers,† by anatomic site, sex, age, race, and ethnicity§ — United States, 2008–2012¶
|Characteristic||Cervical carcinoma||Vaginal SCC||Vulvar SCC||Penile SCC||Rectal SCC|
|Age group (yrs)|
|American Indians/Alaska Natives||6.3§§||113||0.3||5||1.1§§||16||0.7||8||—||—||—||—|
|Characteristic||Oropharyngeal SCC||Anal SCC|
|Female||Male||Female and male||Female||Male||Female and male|
|Age group (yrs)|
|American Indians/Alaska Natives||0.9§§||16||4.4§§||66||2.6§§||81||0.9§§||15||0.5§§||7||0.7§§||22|
TABLE 2. State incidence* of human papillomavirus (HPV)-associated cancers,† by cancer site and sex — National Program of Cancer Registries and Surveillance, Epidemiology, and End Results program, United States, 2008–2012§
|State/Territory||Cervical||Vaginal||Vulvar||Penile||Anal||Rectal||Oropharyngeal||HPV-associated cancers combined|
|Female||Female||Female||Male||Male and female||Male||Female||Male and female||Male||Female||Male and female||Male||Female||Male and female||Male||Female|
|District of Columbia||9.2||—¶||1.7||—¶||2.4||2.7||2.0||—¶||—¶||—¶||5.2||8.9||2.2||14.3||12.8||15.9|
TABLE 3. Estimated average annual percentage and estimated number of cancers attributable to human papillomavirus (HPV),* by anatomic site and sex — United States, 2008–2012†
|Cancer||Average annual no.||Attributable to any HPV type§||Attributable to HPV 16/18§||Attributable to HPV 31/33/45/52/58§||Attributable to HPV 16/18/31/33/45/52/58§|
|No. (%)||No. (%)||No. (%)||No. (%)|
|Cervical||11,771||10,700 (90.6)||7,800 (66.2)||1,700 (14.7)||9,500 (80.9)|
|Vaginal||802||600 (75.0)||400 (55.1)||100 (18.3)||600 (73.4)|
|Vulvar||3,554||2,400 (68.8)||1,700 (48.6)||500 (14.2)||2,200 (62.8)|
|Penile||1,168||700 (63.3)||600 (47.9)||100 (9.0)||700 (56.9)|
|All anal cancers||5,010||4,600 (91.1)||4,000 (79.4)||400 (8.2)||4,400 (87.6)|
|Female||3,260||3,000 (92.5)||2,600 (79.5)||400 (10.8)||2,900 (90.3)|
|Male||1,750||1,600 (88.7)||1,400 (79.1)||100 (3.8)||1,500 (82.9)|
|All rectal cancers||750||700 (91.1)||600 (79.4)||100 (8.2)||700 (87.6)|
|Female||513||500 (92.5)||400 (79.5)||100 (10.8)||500 (90.3)|
|Male||237||200 (88.7)||200 (79.1)||— (3.8)||200 (82.9)|
|All oropharyngeal cancers||15,738||11,000 (70.1)||9,500 (60.2)||900 (5.7)||10,400 (65.9)|
|Female||3,100||2,000 (63.3)||1,600 (50.8)||300 (9.5)||1,900 (60.3)|
|Male||12,638||9,100 (72.4)||8,000 (63.4)||600 (4.4)||8,600 (67.8)|
|Total||38,793||30,700 (—)||24,600 (—)||3,800 (—)||28,500 (—)|
Suggested citation for this article: Viens LJ, Henley SJ, Watson M, et al. Human Papillomavirus–Associated Cancers — United States, 2008–2012. MMWR Morb Mortal Wkly Rep 2016;65:661–666. DOI: http://dx.doi.org/10.15585/mmwr.mm6526a1external icon.
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