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Human papillomavirus–attributable cancers in the United States, 2012–2016

Human papillomavirus ( HPV ) causes nearly all cervical cancers and some cancers of the vagina, vulva, penis, anus, and oropharynx.
Most HPV infections are asymptomatic and clear spontaneously within 1 to 2 years; however, persistent infection with oncogenic HPV types can lead to development of precancer or cancer.
In the United States, the 9-valent HPV vaccine ( 9vHPV ) is available to protect against oncogenic HPV types 16, 18, 31, 33, 45, 52, and 58 as well as nononcogenic types 6 and 11 that cause genital warts.

CDC ( Centers for Disease Control and Prevention ) have analyzed data from the U.S. Cancer Statistics ( USCS ) to assess the incidence of HPV-associated cancers and to estimate the annual number of cancers caused by HPV, overall and by state, during 2012–2016.

An average of 43,999 HPV-associated cancers were reported annually, and an estimated 34,800 ( 79% ) of those cancers were attributable to HPV. Of these 34,800 cancers, an estimated 32,100 ( 92% ) were attributable to the types targeted by 9vHPV, with 19,000 occurring among females and 13,100 among males.
The most common were cervical ( 9,700 ) and oropharyngeal cancers ( 12,600 ).
The number of cancers estimated to be attributable to the types targeted by 9vHPV ranged by state from 40 to 3,270 per year.

HPV vaccination is an important strategy that could prevent these cancers, but during 2018, only half of adolescents were up to date on HPV vaccination.

CDC analyzed cancer incidence data from USCS, which includes cancer registry data from CDC’s National Program of Cancer Registries and the National Cancer Institute’s Surveillance, Epidemiology, and End Results Program.
Cancers are not tested for HPV in most cancer registries; therefore, HPV-associated cancers were defined as invasive cancers at anatomic sites with cell types in which HPV DNA frequently is found, including carcinomas of the cervix ( i.e., squamous cell cancers [ SCC ], adenocarcinomas, and other carcinomas ) and SCC of the vulva, vagina, penis, oropharynx, and anus ( including rectal SCC ).
Oropharyngeal SCC included squamous cell cancer types at the base of tongue, pharyngeal tonsils, anterior and posterior tonsillar pillars, glossotonsillar sulci, anterior surface of soft palate and uvula, and lateral and posterior pharyngeal walls.
Anal SCC also included rectal SCCs because they are biologically similar and might be misclassified.

HPV-associated cancer incidence rates were calculated using reported cases as the numerator and modification of annual county population estimates as the denominator, standardized to the 2000 U.S. standard population and expressed as cases per 100,000 persons.
The USCS data, including the numbers and rates of HPV-associated cancers, are available to the public through the USCS Data Visualizations Tool. To estimate the number of HPV-attributable cancers ( cancers that are probably caused by HPV ), the average annual number of HPV-associated cancers was multiplied by the percentage of each cancer type found to be attributable to HPV in a large U.S. study using HPV genotyping. Estimates of HPV-attributable cancers were rounded to the nearest 100 for national data and to the nearest 10 for state-level data.
Cancers were grouped as those attributable to the types targeted by 9vHPV, to other HPV types, and HPV-negative cancers ( those that occur at anatomic sites in which HPV-associated cancers are often found but do not have detectable HPV DNA ).
The percentage of HPV-negative cancers was calculated as the difference between the total HPV-associated cancers and the HPV-attributable estimates.

During 2012–2016, an average of 43,999 HPV-associated cancers ( 12.2 per 100,000 persons ) were reported annually, and an estimated 79% ( 34,800 ) of these cancers were attributable to HPV. Of these cancers, an estimated 32,100 ( 92% ) were attributable to the types targeted by 9vHPV.
The largest number were oropharyngeal cancer ( 12,600 ), followed by cervical ( 9,700 ), anal ( 6,000 ), vulvar ( 2,500 ), penile ( 700 ), and vaginal cancers ( 600 ).
Among cancers estimated to be attributable to the types targeted by 9vHPV, 19,000 ( 59% ) occurred among females, and 13,100 ( 41% ) occurred among males.

The annual number of cancers estimated to be attributable to the types targeted by 9vHPV ranged by state from 40 ( Wyoming ) to 3,270 ( California ).
Oropharyngeal cancer was the most common cancer estimated to be attributable to types targeted by 9vHPV in most states, except in Texas, where cervical cancer was most common and in Alaska, DC, New Mexico, and New York, where estimates of oropharyngeal and cervical cancers attributable to the types targeted by 9vHPV were the same.

Each year during 2012–2016, an estimated average of 34,800 HPV-attributable cancers were diagnosed in the United States, and 92% ( 32,100 ) were attributable to the HPV types targeted by 9vHPV.
Previous annual estimates of cancers attributable to the types targeted by 9vHPV were 28,500 for 2008–2012, 30,000 for 2010–2014, and 31,200 for 2011–2015.
The higher estimates in more recent years are, in part, due to an aging and growing population and increases in oropharyngeal, anal, and vulvar cancers.

HPV vaccination is an important component of cancer prevention, yet only about half of adolescents are up to date on this vaccine.
The Advisory Committee on Immunization Practices recommends routine HPV vaccination at age 11–12 years and catch-up HPV vaccination for all persons through age 26 years.
Catch-up vaccination is not recommended for all adults aged more than 26 years because the benefit of HPV vaccination decreases in older age groups; however, vaccination based on shared clinical decision-making can be considered for some persons aged 27–45 years who are not adequately vaccinated.

In 2018, HPV vaccination coverage varied by state, and no state met the Healthy People 2020 objective for HPV vaccination ( receipt of 2 or 3 doses of HPV vaccine by 80% of adolescents aged 13–15 years ).
State efforts to meet the Healthy People 2020 objective for HPV vaccination could reduce geographic disparities in HPV-associated cancer incidence in the future.

Cervical cancer is the only HPV-associated cancer for which screening is routinely recommended.
Recommendations state that women aged 21–65 years be screened regularly for cervical precancers and cancers. Women aged 21–29 years should be screened with the Papanicolaou ( Pap ) test every 3 years. Women aged 30–65 years can be screened with one of three strategies: the Pap test every 3 years, an HPV test every 5 years, or both a Pap and HPV test every 5 years.
Regardless of screening strategy, all abnormal test results require follow-up of abnormal results and appropriate treatment.
The Healthy People 2020 target for cervical cancer screening coverage is 93%; however, in 2015 only 81% of women aged 21–65 years reported receiving a Pap test within the past 3 years; coverage was lower among Asians, Hispanics, non–U.S. born, and uninsured women.

Progression from persistent HPV infection to precancers and eventually invasive cancer occurs over many years, so it might be too soon to see the effects of HPV vaccination on invasive cancers.
However, several studies have demonstrated the population-level impact of HPV vaccination in the United States, including a reduction in the prevalence of vaccine-type HPV infection and rates of high-grade cervical precancers in women aged less than 25 years.
Cervical cancer rates declined 1.6% per year during 1999–2015, largely because of screening, although decreases among the youngest age group of women might be due in part to HPV vaccination.

The findings in this report are subject to at least one limitation. Although population-based cancer registries provide a reliable system for counting invasive cancers, they do not routinely collect or report information on HPV genotype status in cancer tissue; actual counts of HPV-associated cancers can be provided, but for HPV-attributable cancers, only estimates are available.
An important strength of this study, however, is the use of high-quality, population-based surveillance data with 100% coverage of the U.S. population, allowing for specific histologic definitions to monitor HPV-associated cancer incidence nationally and in each state.

Among the 43,999 HPV-associated cancers that occur each year in the United States, an estimated 34,800 are attributable to HPV, including 32,100 attributable to HPV types targeted by 9vHPV.
During 2018, only half of adolescents were up to date on HPV vaccination.
Surveillance for HPV-associated cancers using population-based cancer registries with high-quality data and the assessment of HPV-attributable cancers can be used to monitor the long-term impact of HPV vaccination and current cervical cancer screening strategies in the United States.
The examination of state-level data enables states to plan for and monitor the impact of vaccination and cervical cancer screening. ( Xagena )

Source: CDC - Centers for Disease Control and Prevention, 2019