Trends in Human Papillomavirus–Associated Cancers — United States, 1999–2015

Human papillomavirus (HPV) is a known cause of cervical cancer, as well as some oropharyngeal, vulvar, vaginal, penile, and anal cancers. To assess trends, characterized by average annual percent change (AAPC), in HPV-associated cancer incidence during 1999–2015, CDC analyzed data from cancer registries covering 97.8% of the U.S. population. A total of 30,115 new cases of HPV-associated cancers were reported in 1999 and 43,371 in 2015. During 1999–2015, cervical cancer rates decreased 1.6% per year; vaginal squamous cell carcinoma (SCC) rates decreased 0.6% per year; oropharyngeal SCC rates increased among both men (2.7%) and women (0.8%); anal SCC rates also increased among both men (2.1%) and women (2.9%); vulvar SCC rates increased (1.3%); and penile SCC rates remained stable. In 2015 oropharyngeal SCC (15,479 cases among men and 3,438 among women) was the most common HPV-associated cancer. Continued surveillance through high-quality cancer registries is important to monitor cancer incidence and trends in these potentially preventable cancers.

Rates of oropharyngeal SCC increased among men in all age groups ≥40 years, ranging from 0.8% among men aged 40-49 years to 4.0% among those aged 60-69 years ( Table 1). Rates varied by race, with the largest increase occurring among white men (3.3%), and by region, with rates increasing more in the Midwest (3.2%) than in other regions ( Table 2).
During 1999-2015 cervical carcinoma rates were stable among women aged 35-39 years and decreased among women aged 20-34 years and aged ≥40 years, decreasing >3% per year among women aged 20-24 years and ≥70 years ( Table 1). Cervical carcinoma rates decreased among all racial/ethnic groups, more among Hispanics than among non-Hispanics, and more in the West than in all other regions ( Table 2). During 1999-2015 vaginal SCC decreased 0.6% per year.
Anal SCC rates increased among women (2.9% per year) and men (2.1%) during this period. The largest increases in anal SCC rates were among women aged 50-69 years ( per year) and men aged 50-59 years (4.0%). Anal SCC rates increased among white women (3.2% per year), black women (2.2%), white men (2.1%), and black men (3.0%). Anal SCC rates increased among both men and women in all regions except among men in the West region; the largest rate increases were among women in the Northeast (4.3% per year) and Midwest (3.6%).

Discussion
HPV-associated cancer rates changed from 1999 to 2015. Rates increased for oropharyngeal SCC, anal SCC and vulvar SCC, decreased for cervical carcinoma and vaginal SCC, and remained stable for penile SCC.
The decline in cervical cancer from 1999 to 2015 represents a continued trend since the 1950s as a result of cancer screening (4). Rates of cervical carcinoma in this report decreased more among Hispanics, American Indian/Alaska Natives, and blacks than other groups; however, incidence rates were

Summary
What is already known about this topic?
Human papillomavirus (HPV) can cause some types of cervical, vulvar, vaginal, penile, anal, and oropharyngeal cancers.
What is added by this report?
Oropharyngeal squamous cell carcinoma is now the most common HPV-associated cancer. During 1999-2015 cervical carcinoma incidence rates decreased 1.6% per year, and oropharyngeal SCC incidence rates increased 2.7% per year among men and 0.8% per year among women.
What are the implications for public health practice?
Population-based screening is recommended for only one HPV-associated cancer (cervical) at this time; however, HPV vaccination can prevent infection with the HPV types most strongly associated with cancer. Ongoing surveillance for HPV-associated cancers using high-quality population-based registries is critical to monitor cancer rates and trends. still higher among Hispanics and blacks than among whites in 2015. These persistent disparities in incidence suggest that health care delivery needs of some groups are not fully met.
Several factors could contribute to the increase in oropharyngeal and anal cancers including changing sexual behaviors. Unprotected oral sex and receptive anal sex are risk factors for HPV infection (2,5). White men have the highest number of lifetime oral sex partners and report first performing oral sex at a younger age compared with other racial/ethnic groups; these risk factors could be contributing to a higher rate of oropharyngeal SCC among white men than other racial/ethnic groups (6). Although smoking is a risk factor for oropharyngeal cancers, smoking rates have been declining in the United States, and studies have indicated that the increase in oropharyngeal cancer is attributable to HPV (5). In contrast to cervical cancer, there currently is no U.S. Preventive Services Task Force recommended screening for other HPV-associated cancers (7).
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, registries do not routinely determine the HPV status of cancers. In the United States, HPV DNA has been determined through special studies and found in 91% of cervical, 91% of anal, 75% of vaginal, 70% of oropharyngeal, 69% of vulvar, and 63% of penile cancers (1). Second, reporting of race and ethnicity uses data from medical records, which might be inaccurate in a small proportion of cases. An important strength of this study is the use of high quality population-based surveillance data with 97.8% coverage of the U.S. population, allowing for specific histologic definitions to monitor HPV-associated cancer trends. Measures to prevent HPV-associated diseases in the United States include both females and males; HPV vaccination was included in the routine immunization program for females in 2006 and for males in 2011. Although it might be too soon for effects on invasive cancers from HPV vaccination in the United States, studies have reported reductions in cervical HPV infection, genital warts, and cervical precancers (8). Most cervical cancers are preventable with both HPV vaccination and regular and timely screening among women aged 21-65 years with follow-up for abnormal test results. Routine HPV vaccination is recommended at age 11 or 12 years; currently, the 9-valent HPV vaccine, which targets oncogenic types attributed to 73% of HPV-associated cancers, is being used in the United States (1,9). Further research to understand the progression from HPV infection to oropharyngeal cancer would be beneficial. Continued surveillance through high-quality registries is important to monitor changes in HPV-associated cancer incidence.