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

Elizabeth A. Van Dyne, MD; S. Jane Henley, MSPH; Mona Saraiya, MD; Cheryll C. Thomas, MSPH; Lauri E. Markowitz, MD; Vicki B. Benard, PhD

Disclosures

Morbidity and Mortality Weekly Report. 2018;67(33):918-924. 

In This Article

Abstract and Introduction

Introduction

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.

HPV causes cervical cancer and some types of oropharyngeal, vulvar, vaginal, penile, and anal cancer; HPV DNA is found in specific tissue types that include carcinomas of the cervix and SCCs of the vulva, vagina, penis, oropharynx, and anus.[1,2] The natural history from HPV infection to precancerous lesion to invasive cervical cancer is well established. HPV is the most commonly sexually transmitted infection in the United States and is often acquired soon after initiating sexual activity.[3] Studies indicate that approximately 90% of new cervical HPV infections, including types that cause cancer, clear or become undetectable within 2 years, and those that do not clear take decades to progress to invasive cervical cancer.* Less is known about carcinogenic progression of HPV-associated infection at other anatomic sites.[2]

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 that met the criteria for high data quality for all years from 1999 to 2015; these data cover approximately 97.8% of the U.S. population. Invasive cancers are not tested for HPV in most cancer registries; therefore, an HPV-associated cancer was defined as an invasive malignancy in which HPV DNA was frequently found in special studies, including carcinomas of the cervix (i.e., SCC, adenocarcinomas, and other carcinomas) and SCC of the vulva, vagina, penis, oropharynx, and anus (including rectal SCC)[2] and was microscopically confirmed.§ Cases were classified by anatomic site and cell type using the International Classification of Diseases for Oncology, Third Edition. 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. Age-adjusted incidence rates were calculated per 100,000 persons and standardized to the 2000 U.S. standard population. Trends were measured with AAPC in rates calculated using joinpoint regression. Rates were considered to increase if the AAPC was greater than zero (p<0.05) and to decrease if the AAPC was less than zero (p<0.05); otherwise, rates were considered stable. A maximum of two joinpoints was used. Rates and trends were estimated by sex, age group, race,** ethnicity,†† and region.§§

In the United States, a total of 30,115 new cases of HPV-associated cancer were reported in 1999 and 43,371 in 2015 (Table 1). In 1999, cervical carcinoma (13,125 cases) was the most common HPV-associated cancer: 3,750 more cases of cervical carcinoma than of oropharyngeal SCC were identified. During 1999–2015 cervical carcinoma rates decreased 1.6% per year, and oropharyngeal SCC rates increased 2.7% per year among men and 0.8% per year among women (Figure 1) (Figure 2). In 2015, there were 11,788 reported cases of cervical carcinoma and 18,917 cases of oropharyngeal SCC, including 15,479 (82%) among men and 3,438 (18%) among women.

Figure 1.

Trends* in age-adjusted incidence of cervical carcinoma among females and oropharyngeal SCC among men, — United States,§ 1999–2015
Sources: CDC's National Program of Cancer Registries; National Cancer Institute's Surveillance, Epidemiology, and End Results program.
Abbreviations: AAPC=average annual percent change; NS=not significant; SCC = squamous cell carcinoma.
*Trends were measured with AAPC in age-adjusted rates, and were considered to increase or decrease if p<0.05; otherwise trends were considered stable.
HPV-associated cancers were defined as cancers at specific anatomic sites with specific cell types in which HPV DNA frequently is found. All cancers were microscopically confirmed. Cervical cancers (International Classification of Diseases for Oncology, Third Edition [ICD-O-3] site codes C53.0–C53.9) are limited to carcinomas (ICD-O-3 histology codes 8010–8671, 8940–8941). Oropharyngeal (ICD-O-3 site codes C01.9, C02.4, C02.8, C05.1, C05.2, C09.0, C09.1, C09.8, C09.9, C10.0, C10.1, C10.2, C10.3, C10.4, C10.8, C10.9, C14.0, C14.2 and C14.8) cancer sites are limited to squamous cell carcinomas (ICD-O-3 histology codes 8050–8084, 8120–8131).
§Cancer incidence compiled from cancer registries that meet the data quality criteria for all invasive cancer sites combined for each year during the period 1999–2015 (covering 97.8% of the U.S. population).

Figure 2.

Trends* in age-adjusted HPV-associated cancer incidence, by cancer type and sex — United States,§ 1999–2015
Sources: CDC's National Program of Cancer Registries; National Cancer Institute's Surveillance, Epidemiology, and End Results program.
Abbreviations: AAPC=average annual percent change; HPV = human papillomavirus; NS=not significant; SCC = squamous cell carcinoma.
*Trends were measured with AAPC in age-adjusted rates, and were considered to increase or decrease if p<0.05; otherwise trends were considered stable.
HPV-associated cancers were defined as cancers at specific anatomic sites with specific cell types in which HPV DNA frequently is found. All cancers were microscopically confirmed. Vaginal (International Classification of Diseases for Oncology, Third Edition [ICD-O-3] site code C52.9), vulvar (ICD-O-3 site codes C51.0–C51.9), penile (ICD-O-3 site codes C60.0–60.9), anal (including rectal SCC; ICD-O-3 site code C20.9, C21.0–C21.9), and oropharyngeal (ICD-O-3 site codes C01.9, C02.4, C02.8, C05.1, C05.2, C09.0, C09.1, C09.8, C09.9, C10.0, C10.1, C10.2, C10.3, C10.4, C10.8, C10.9, C14.0, C14.2 and C14.8) cancer sites are limited to squamous cell carcinomas (ICD-O-3 histology codes 8050–8084, 8120–8131).
§Cancer incidence compiled from cancer registries that meet the data quality criteria for all invasive cancer sites combined for each year during the period 1999–2015 (covering 97.8% of the U.S. population).

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.

In contrast, penile SCC rates were stable, and vulvar SCC rates increased 1.3% per year (Table 1) (Figure 2). Specifically, vulvar SCC rates increased during 1999–2015 among women aged 50–69 years, among whites (1.5%), and blacks (1.0%), and in the Northeast (1.5%), Midwestern (1.5%), and Southern (1.3%) regions of the United States.

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 (4.6%–4.8% 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%).

*Manual for the Surveillance of Vaccine-Preventable Diseases, Chapter 5: Human Papillomavirus (HPV). https://www.cdc.gov/vaccines/pubs/surv-manual/chpt05-hpv.html.
Cancer registries' incidence data met the following five United States Cancer Statistics criteria: 1) ≤5% of cases ascertained solely on the basis of death certificate; 2) ≤3% of cases missing information on sex; 3) ≤3% of cases missing information on age; 4) ≤5% of cases missing information on race; and 5) ≥97% of registry's records passed a set of single-field and interfield computerized edits that test the validity and logic of data components. https://gis.cdc.gov/Cancer/USCS/DataViz.html.
§HPV-associated cancers were defined as cancers at specific anatomic sites with specific cell types in which HPV DNA frequently is found. All cancers were microscopically confirmed. Cervical cancers (ICD-O-3 http://codes.iarc.fr/ [ICD-O-3] site codes C53.0–C53.9) are limited to carcinomas (ICD-O-3 histology codes 8010–8671, 8940–8941). Vaginal (ICD-O-3 site code C52.9), vulvar (ICD-O-3 site codes C51.0–C51.9), penile (ICD-O-3 site codes C60.0–60.9), anal (including rectal SCC; ICD-O-3 site code C20.9, C21.0–C21.9), and oropharyngeal (ICD-O-3 site codes C01.9, C02.4, C02.8, C05.1, C05.2, C09.0, C09.1, C09.8, C09.9, C10.0, C10.1, C10.2, C10.3, C10.4, C10.8, C10.9, C14.0, C14.2 and C14.8) cancer sites are limited to squamous cell carcinomas (ICD-O-3 histology codes 8050–8084, 8120–8131). Anal and rectal SCC were combined into a single category "anal SCC" because a very small subset of rectal cancers (i.e. the SCCs, around 700 per year) are similar to anal SCC.
https://surveillance.cancer.gov/joinpoint/.
**Population estimates incorporate bridged single-race estimates derived from the original multiple-race categories in the 2010 U.S. Census. https://seer.cancer.gov/popdata.
†† https://www.census.gov/prod/cen2010/briefs/c2010br-04.pdf.
§§ Midwest: Illinois, Indiana, Iowa, Kansas, Michigan, Minnesota, Missouri, Nebraska, North Dakota, Ohio, and Wisconsin. Northeast: Connecticut, Maine, Massachusetts, New Hampshire, New Jersey, New York, Pennsylvania, Rhode Island, and Vermont. South: Alabama, Delaware, District of Columbia, Florida, Georgia, Kentucky, Louisiana, Maryland, North Carolina, Oklahoma, South Carolina, Tennessee, Texas, Virginia, and West Virginia. West: Alaska, Arizona, California, Colorado, Hawaii, Idaho, Montana, Nevada, New Mexico, Oregon, Utah, Washington, and Wyoming.

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