HPV-Associated Cancers in the United States, 1998–2003: Questions and Answers

Key Points

• In order to monitor the impact of the HPV vaccine on the incidence of HPV-associated cancers and precancers in the United States, baseline cancer data collected prior to widespread immunization are critical.



• During 1998–2003, there was an average of nearly 25,000 HPV-associated cancers per year in the United States, with an incidence rate of 10.6 per 100,000 persons.



• The top HPV-associated cancer sites were cervix, oral cavity and oropharynx, anus, vulva, penis, and vagina.



• Both lower education and higher poverty were associated with increased risks for HPV-associated cancers of the cervix, penis, and vagina.



• Among women with a first primary diagnosis of cervical cancer, there is a statistically significant increased risk of developing subsequent in situ cancers of the vagina and vulva, and invasive cancers of the vagina, vulva, and rectum.

Questions

1. What is the purpose of these reports and who created them?
2. What are the sources of the data?
3. What is happening with incidence rates for HPV-associated cancers overall?
4. How do these data differ from the usual reports of cancer at these sites?
5. What is happening with incidence rates for HPV-associated cervical cancers?
6. What is happening with incidence rates for HPV-associated cancers of the oral cavity and oropharynx
7. What is happening with incidence rates for HPV-associated cancers of the anus?
8. What is happening with incidence rates for HPV-associated cancers of the vulva?
9. What is happening with incidence rates for HPV-associated cancers of the penis?
10. What is happening with incidence rates for HPV-associated cancers of the vagina?
11. What is happening with multiple primaries and HPV-associated cancers?
12. What is happening with HPV-associated precancers?
13. How do HPV-associated cancer incidence rates differ by geographic region
14. How do HPV-associated cancer incidence rates differ by race and socio-economic status?
15. What do we know about treatment for HPV-associated cancers?
16. How are disparity issues being addressed for prevention of HPV-associated cancers?
17. What do we know about the HPV vaccine?
18. What additional steps are needed to monitor the impact of the HPV vaccine on precancers or cancers?
19. How might cervical cancer screening be affected with the HPV vaccine?
20. How are cancer incidence and death rates presented?
21. Where is this report published?
22. Where can I find out more about HPV and the HPV vaccine?

1. What is the purpose of these reports and who created them?

These reports provide baseline data about the occurrence of human papillomavirus (HPV)-associated cancers in the United States prior to widespread immunization against specific oncogenic types of HPV. These data and data to be collected in the future are critical for monitoring the impact of the HPV vaccine on the incidence of HPV-associated cancers and precancers. These studies were conducted by scientists at the CDC, cancer registry staff and researchers in several states across the country, the National Cancer Institute, and the American Cancer Society.

2. What are the sources of the data?

Information on newly diagnosed cancer cases (incidence) occurring in the United States is based on data collected by registries in the CDC's National Program of Cancer Registries (NPCR) and NCI's Surveillance, Epidemiology, and End Results (SEER) Program. Established by Congress through the Cancer Registries Amendment Act in 1992, the NPCR collects data on the occurrence of cancer; the type, extent, and location of the cancer; and the type of initial treatment. NPCR supports central cancer registries in 45 states, the District of Columbia, Puerto Rico, and the U.S. Pacific Island jurisdictions. SEER currently collects and publishes cancer incidence and survival data from population-based cancer registries covering approximately 26 percent of the U.S. population. Together, NPCR and the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program collect data for the entire U.S. population.

Cancer mortality information in the United States is based on causes of death reported by physicians on death certificates and filed by state vital statistics offices. The mortality information is processed and consolidated in a national database by CDC through the National Vital Statistics System, which covers the entire United States.

Survival after a diagnosis of cancer information in the United States is based on data from the NCI's SEER Program. Five-year relative survival rates were examined by the life table method and are based on follow-up for vital status into 1994.

The Incidence of HPV-Associated Cancers

3. What is happening with incidence rates for HPV-associated cancers overall?

During 1998–2003, the incidence rate of HPV-associated cancers in the United States was 10.6 per 100,000 people. The top HPV-associated cancer sites were cervix, oral cavity and oropharynx, anus, vulva, penis, and vagina.¹

4. How do these data differ from the usual reports of cancer at these sites?

This report uses standardized criteria on all HPV-associated cancers type using standardized criteria through a consensus of cancer registry and subject matter experts. To focus on cancers that were potentially HPV-associated, most analyses were restricted by histology, or cell type. Cervical cancer was limited to all carcinomas including squamous cell and adenocarcinomas. All other sites were limited to squamous cell carcinomas. In addition, analyses of head and neck cancers were restricted by anatomic subsites most likely to be HPV-associated, called "oral cavity and oropharynx."¹

5. What is happening with incidence rates for HPV-associated cervical cancers?

More HPV-associated cancers occur in the uterine cervix than at any other site. The incidence rate of cervical cancer was 8.9 per 100,000 females during 1998–2003. Over 70% of all cervical cancers were squamous cell carcinomas, and nearly 20% were adenocarcinomas. Black and Hispanic women had higher rates of cervical cancer and, more specifically, squamous cell cervical cancer, than white and non-Hispanic women.²

6. What is happening with incidence rates for HPV-associated cancers of the oral cavity and oropharynx?

During 1998–2003, 43.6% of HPV-associated cancers of the oral cavity and oropharynx occurred in the tonsils and 38.4% occurred in the base of the tongue. Rates of HPV-associated oral cavity and oropharyngeal cancers were highest among blacks, non-Hispanics, and men. Incidence rates for HPV-associated cancers of the tonsils and tongue each significantly increased 3.0% per year during 1998–2003; rates for HPV-unrelated subsites decreased during the same time period.³

7. What is happening with incidence rates for HPV-associated cancers of the anus?

HPV-associated anal cancer disproportionately affected women (1.5 per 100,000 females) compared to men (1.0 per 100,000 males). During 1998–2003, 85% of anal cancers were squamous cell carcinomas. Among women over age 60, rates were higher among Hispanic women than women of other races or ethnicities. Among men under age 60, rates were higher among black men than men of other races or ethnicities. Regardless of stage at diagnosis, men with anal cancer were less likely to survive five years after diagnosis compared to women.⁴

8. What is happening with incidence rates for HPV-associated cancers of the vulva?

During 1998–2003, squamous cell carcinomas accounted for 77% of in situ cases and 75% of invasive vulvar cancers. White women had higher rates of vulvar squamous cell carcinomas than black and Asian/Pacific Islander women. Five-year relative survival was greatest for white (86%) and black (85%) women and lowest for Asian/Pacific Islander (69%) women.⁵

9. What is happening with incidence rates for HPV-associated cancers of the penis?

During 1998–2003, 92.7% of cancers of the penis were squamous cell carcinomas. Penile cancer incidence and death rates were higher in Hispanic than non-Hispanic men. Death rates from cancer of the penis were higher among black compared to white men. Penile cancer incidence and death rates were highest in the southern states and in high poverty and low education regions.⁶

10. What is happening with incidence rates for HPV-associated cancers of the vagina?

Squamous cell carcinoma was the most common vaginal cancer cell type (74% of in situ cases and 66% of invasive cases). Compared to white women, the incidence rate of invasive vaginal squamous cell carcinoma (SCC) among black women was 72% higher, while the rate among Asian/Pacific Islander women was 34% lower. Hispanic women had a 38% higher rate of this malignancy than non-Hispanic women. Black, API, Hispanic, and older women were more likely to be diagnosed with late stage disease, and these groups had lower 5-year relative survival rates than their white, non-Hispanic, and younger counterparts.⁷

11. What is happening with multiple primaries and HPV-associated cancers?

Among women with a first primary diagnosis of cervical cancer, there is a statistically significant increased risk of developing subsequent in situ cancers of the vagina and vulva, and invasive cancers of the vagina, vulva, and rectum. Women of all racial and ethnic populations studied had elevated risks for subsequent primary diagnoses of in situ and invasive vaginal cancers.⁸

12. What is happening with HPV-associated precancers?

Understanding the burden of in situ (a type of precancer) disease is important for monitoring the impact of HPV vaccine and ideally, would allow us to measure some impacts earlier. Cancer registries can collect in situ cancers of the vagina, vulva, and anus, but not all of them collect it and report it to the same degree, resulting in underestimates of these precancers. Additionally, not all HPV-associated precancers are collected in the cancer registries. Ever since 1996, all cancer registries besides Michigan stopped collecting cervical precancers. During 1985–2003, 83.0% of cervical cancers diagnosed among women residing in Michigan were in situ and 31.7% were invasive. Rates of in situ disease increased from 31.7 per 100,000 in 1985 to 59.2 per 100,000 in 2003 while rates of invasive disease decreased (11.7 per 100,000 in 1985, 7.8 per 100,000 in 2003).⁹

HPV-Associated Cancers in Special Populations

13. How do HPV-associated cancer incidence rates differ by geographic region

During 1998–2003, incidence rates of HPV-associated cancers varied appreciably by state. Rates of cervical cancer, for example, were at least 10.0 per 100,000 women in the District of Columbia, Florida, Illinois, Kentucky, Louisiana, West Virginia, Arkansas and Texas; rates were below 7.0 per 100,000 women in Idaho, Massachusetts, Minnesota, and Utah.¹

For five states in Appalachia combined (Alabama, Kentucky, Ohio, Pennsylvania, and West Virginia), invasive cervical cancer incidence rates were higher in the Appalachian areas than non-Appalachian areas. Rates were also higher in rural compared to urban areas of the states.¹⁰

Along the U.S. Mexico border in 1998–2003, invasive cervical cancer incidence rates were twice as high among Hispanic women as non-Hispanic women in border counties. Hispanic women in border states had higher rates compared to Hispanic women in non-border states.¹¹

14. How do HPV-associated cancer incidence rates differ by race and socio-economic status?

Incidence rates of HPV-associated cancers varied by sex, cancer site, and the particular measure of socio-economic status (education, household income, and poverty level). Among men, both lower education and higher poverty appeared to be associated with increased incidence rates for HPV-associated cancer of the penis. Among women, both lower education and higher poverty appeared to be associated with increased rates of HPV-associated cervical and vaginal cancers.¹²

Overall, Asian and Pacific Islander men and women had lower rates of HPV-associated cancers than white men and women. In California, the state with the largest Asian and Pacific Islander population in the United States, cervical cancer incidence rates vary by Asian population. Vietnamese and Korean women had greater cervical cancer incidence and death rates than non-Hispanic white women, while rates among Chinese, Japanese, and South Asians were comparable or lower.¹³

Black and Hispanic women had higher rates of HPV-associated cervical cancer than white women. Black women also appeared to have higher rates of HPV-associated vaginal cancer. Black men and women appeared to have higher rates of HPV-associated cancers of the oropharynx and oral cavity. Hispanic men had higher rates of HPV-associated penile cancer than non-Hispanic men.¹

Treatment and Programs

15. What do we know about treatment for HPV-associated cancers?

The choice of treatment (surgery, radiation therapy) for HPV-associated gynecologic carcinomas was associated with demographic and clinical (cancer stage, histology) factors. Atypical tumor histology and selected demographic factors (age 30 to 64 years, Asian/ Pacific Islander race, married) were associated with having a hysterectomy. Black women were least likely to undergo hysterectomy. Overall, the utilization of hysterectomy to treat gynecologic cancers decreased slightly between 1992 and 2004, although the frequency increased in the Hispanic population subgroup.¹⁴

16. How are disparity issues being addressed for prevention of HPV-associated cancers?

Greater awareness of programs and services available to the underserved in communities across the U.S. may be one of the most important steps in the fight against cervical cancer. Three federal programs with the potential to reduce cervical cancer incidence, morbidity, and mortality are administered by the Centers for Disease Control and Prevention (CDC): the National Breast and Cervical Cancer Early Detection Program (NBCCEDP), the Vaccines for Children Program, and the Section 317 immunization grant program. These complementary programs provide prevention and screening services at no cost to females belonging to the U.S. populations most vulnerable to developing and dying from cervical cancer.¹⁵

• CDC's National Breast and Cervical Cancer Early Detection Program funds all 50 states to build and support infrastructure and provide screening services.



• CDC's National Comprehensive Cancer Control Program. These programs have helped address cancer disparities by supporting cancer control coalitions in each state and to develop and implement cancer control plans in communities across the United States.



• CDC's Vaccines for Children Program is a federally funded program that provides vaccines at no cost to children who might not otherwise be vaccinated because of inability to pay. Children who are eligible for VFC vaccines are entitled to receive pediatric vaccines that are recommended by the Advisory Committee on Immunization Practices.



• CDC's Section 317 Grant Program works to ensure that children, adolescents, and adults receive appropriate immunizations by partnering with healthcare providers in the public and private sectors. Most children served through Section 317 are underinsured or their parents are working poor who cannot afford the deductibles required to fully vaccinate their children.

Information about the HPV Vaccine

17. What do we know about the HPV vaccine?

A quadrivalent HPV vaccine to prevent HPV types 6, 11, 16 and 18 was licensed for use in the United States in June, 2006 and an application for Food and Drug Administration licensure was submitted for a bivalent HPV vaccine to prevent HPV types 16, and 18, in March, 2007. In this paper, a brief review of the epidemiology of HPV infection and an overview of prophylactic HPV vaccine and post-vaccine licensure monitoring is provided. Currently in the U.S., the quadrivalent HPV vaccine is recommended for routine immunization of girls 11–12 years of age and catch-up through age 26 years.¹⁶

18. What additional steps are needed to monitor the impact of the HPV vaccine on precancers or cancers?

Using cancer registries to monitor the impact of prophylactic HPV vaccines on rates of HPV-associated cancers, particularly cervical cancer, will require a well-funded, carefully organized national effort guided by a multidisciplinary team of experts. Additional goals of a registry system include:¹⁷

• To systematically monitor age-specific rates of invasive cervical cancer and other invasive HPV-associated cancers



• To systematically monitor age-specific rates of cervical cancer precursors and precursors for other HPV-associated cancers



• To identify the distribution of HPV types associated with HPV-associated carcinoma precursors and invasive carcinoma



• To monitor the incidence of carcinoma precursors and invasive carcinoma along with prevalence of vaccination



• To explore and evaluate methods of linking screening and risk factor data that are already being collected by other surveillance data

19. How might cervical cancer screening be affected with the HPV vaccine?

Although HPV vaccine can prevent many cancers, cervical screening, however, will continue to play an important role for the foreseeable future because many women will not have been vaccinated, and even vaccinated women will not be fully protected against all HPV types that cause cancer. Cervical cancer experts comment on how the critical challenge over the next decade will be to develop age appropriate prevention strategies to effectively integrate vaccination and screening efforts to match screening intensity to a woman's risk of precancer. This will require understanding not only the impact of vaccination on reducing cervical abnormalities, but also the influence of vaccination on screening test performance.¹⁸

How to Read This Report

20. How are cancer incidence and death rates presented?

Incidence rates are for invasive cancers, except as noted otherwise. For selected HPV-associated cancer sites, cancer incidence rates are also reported for in situ cancers (cancer that has not spread to neighboring tissue). Average annual (1998–2003), sex-specific, and age-adjusted incidence rates were based on incidence data from 39 population-based cancer registries, covering about 83 percent of the U.S. population.

Cancer incidence rates and death rates are measured as the number of cases or deaths per 100,000 people per year and are age-adjusted to the 2000 U.S. standard population. When a cancer affects only one gender—for example, prostate cancer—then the number is per 100,000 persons of that gender. The numbers are age-adjusted, which allows for comparison of rates from different populations with varying age composition over time and regions.

21. Where is this report published?

The report appeared online on November 3, 2008 at http://www3.interscience.wiley.com/journal/121498429/issue, and in print in the November 15, 2008 supplement to Cancer.

22. Where can I find out more about HPV and the HPV vaccine?

• For more information on HPV, please visit Human Papillomavirus (HPV) Infection.
• For more information on the HPV vaccine, please visit HPV Vaccination.

References

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²Watson M, Saraiya M, Benard V, Coughlin SS, Flowers LC, Cokkinides V, Schwenn M, Huang Y, Giuliano AR. Burden of cervical cancer in the United States, 1998–2003. Cancer 2008;113(S10):2855–2864.

³Ryerson AB, Peters ES, Coughlin SS, Chen VW, Gillison ML, Reichman ME, Wu X, Chaturvedi AK, Kawaoka K. Burden of potentially human papillomavirus-associated cancers of the oropharynx and oral cavity in the US, 1998–2003. Cancer 2008;113(S10):2901–2909.

⁴Joseph DA, Miller JW, Wu X, Chen VW, Morris CR, Goodman MT, Villalon-Gomez JM, Williams M, Cress RD. Understanding the burden of human papillomavirus-associated anal cancers in the US. Cancer 2008;113(S10):2892–2900.

⁵Saraiya M, Watson M, Wu X, King JB, Chen VW, Smith JS, Giuliano AR. Incidence of in situ and invasive vulvar cancer in the US, 1998–2003. Cancer 2008;113(S10):2865–2872.

⁶Hernandez BY, Barnholtz-Sloan J, German RR, Giuliano AR, Goodman MT, King JB, Negoita S, Villalon-Gomez JM. Burden of invasive squamous cell carcinoma of the penis in the United States, 1998–2003. Cancer 2008;113(S10):2883–2891.

⁷Wu X, Matanoski G, Chen VW, Saraiya M, Coughlin SS, King JB, Tao XG. Descriptive epidemiology of vaginal cancer incidence and survival by race, ethnicity, and age in the United States. Cancer 2008;113(S10):2873–2882.

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⁹Copeland G, Datta SD, Spivak G, Garvin AD, Cote M. Total burden and incidence of in situ and invasive cervical carcinoma in Michigan, 1985–2003. Cancer 2008;113(S10):2946–2954.

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