SEARCH

SEARCH BY CITATION

Keywords:

  • methods;
  • human papillomavirus;
  • cancer;
  • surveillance

Abstract

  1. Top of page
  2. Abstract
  3. Data Sources: Cancer Registry and Mortality Surveillance Systems
  4. RESULTS
  5. REFERENCES

Increased attention to human papillomavirus (HPV)-associated cancers in light of the recent release of an HPV vaccine, as well as increased availability of cancer registry data that now include reporting from a large proportion of the US population, prompted the current assessment of HPV-associated cancers. This article describes methods used to assess the burden of HPV-associated cervical, vulvar, vaginal, penile, anal, and oral cavity/oropharyngeal cancers in the United States during 1998 through 2003 using cancer registry data, and it provides a brief overview of the epidemiology of these cancers. Cancer 2008;113(10 suppl):2841–54. Published 2008 by the American Cancer Society.

Persistent infection with the human papillomavirus (HPV) is considered to be a cause of nearly all cervical cancer.1 It is believed that HPV also is associated with approximately 90% of anal cancers; 40% of penile, vaginal, and vulvar cancers; 25% of oral cavity cancers; and 35% of oropharyngeal cancers.2, 3 A quadrivalent HPV vaccine that protects against HPV type 6 (HPV-6), HPV-11, HPV-16, and HPV-18 has been approved for use in the United States for females ages 9 years to 26 years, and a bivalent vaccine that protects against HPV-16 and HPV-18 currently is under review by the US Food and Drug Administration. It has been demonstrated that the HPV vaccine reduces the incidence of cervical, vaginal, and vulvar precancers, offering hope for the reduction in incidence of these diseases and the corresponding invasive cancers among women.4, 5 Current studies are assessing the efficacy of the vaccine on HPV-associated disease in men.6 Close surveillance of these cancers will be necessary to ensure that high-risk populations are being reached by vaccination programs.

Increased attention to HPV-associated cancers in light of the recent release of the vaccine, as well as increased availability of cancer registry data, prompted the current Supplement of Cancer titled “Assessing the Burden of HPV-Associated Cancers in the United States” (ABHACUS). The major purposes of this Supplement are to assess the current burden of anogenital and oropharyngeal cancers associated with HPV within the United States and to provide a baseline for monitoring future trends in HPV-associated cancers. This article describes methods used to assess the burden of HPV-associated cancers in the United States—methods that are common to several articles in the Supplement. This article describes the data sources, case definitions, variables, and analytic methods of descriptive epidemiologic articles that are included in this Supplement, and it provides an overall picture of the burden of HPV-associated cancers.

Data Sources: Cancer Registry and Mortality Surveillance Systems

  1. Top of page
  2. Abstract
  3. Data Sources: Cancer Registry and Mortality Surveillance Systems
  4. RESULTS
  5. REFERENCES

We used cancer incidence data from population-based cancer registries that participate in the Center for Disease Control and Prevention's (CDC's) National Program of Cancer Registries (NPCR) and the National Cancer Institute's (NCI's) Surveillance, Epidemiology, and End Results Program (SEER).7–9 The SEER Program began in 1973 as a result of the National Cancer Act. SEER began collecting and publishing cancer incidence and survival data from 5 state cancer registries and from 4 metropolitan population-based cancer registries covering approximately 10% of the US population. Over time, the program has expanded its coverage of the population to include 9 states and 6 metropolitan areas, in total covering 26% of the population. Recognizing the need for more complete local, state, regional, and national cancer incidence data, Congress established the NPCR in 1992.10 The NPCR now supports cancer registries in 45 states, the District of Columbia, and 3 US territories, and it covers 96% of the population (Fig. 1). NPCR and SEER provide dual support to 4 statewide cancer registries. These SEER metropolitan-area and special population cancer registries report their incidence data to both NCI and to the NPCR statewide cancer registries in their respective states. Together, NPCR and SEER now collect cancer incidence data for the entire US population. Both NPCR data and SEER data are collected and reported by use of standard data items and uniform codes and procedures, as documented by the North American Association of Central Cancer Registries (NAACCR).11 Registries in each program also collect additional data items as required by their funding agencies. Reportable cancers include in situ or invasive primary cancers of all sites except in situ cancer of the cervix, for which collection stopped in 1996.12 Basal and squamous cell carcinomas (SCCs) of the skin are also excluded, with the exception of those on the skin of the genital organs. Cancer cases were coded according to the version of the International Classification of Diseases for Oncology (ICD-O) that was in use at the time of diagnosis. The second edition of the ICD-O (ICD-O-2) was used during the diagnosis years from 1998 through 2000, and the third edition of the ICD-O (ICD-O-3) was used for the diagnosis years from 2001 through 2003; the data from 1998 through 2000 were converted to ICD-O-3 codes.13–16

thumbnail image

Figure 1. States and metropolitan areas supported by the National Program of Cancer Registries, which is administered through the Centers for Disease Control and Prevention, and the Surveillance, Epidemiology, and End Results Program, which is administered through the National Cancer Institute.

Download figure to PowerPoint

Hospitals and other facilities that diagnose or treat cancer collect and report cancer incidence data to central cancer registries (Fig. 2). SEER registries also collect follow-up information for determination of cancer survival statistics. Medical and demographic information for cancer cases is obtained primarily from medical records. Although the majority of cancer cases still are reported by hospitals, data increasingly are obtained from nonhospital sources, such as pathology laboratories, radiation facilities, freestanding surgical centers, long-term care facilities, and physicians' offices. A small percentage (≤5%) of medical and demographic information is obtained solely from death certificates. At the central cancer registries, staff consolidates the data received from hospitals and other facilities and use death certificate data to update the vital status of cases already in the registry.17 These tasks are completed before the data are submitted to either or both federal agencies (Fig. 2). Central cancer registries submit deidentified data to these agencies to be used for publication in statistical and analytic summaries and for release in restricted datasets for research.

thumbnail image

Figure 2. Collection and consolidation of data from patient facilities to federal cancer programs. The National Program of Cancer Registries (NPCR) is administered through the Centers for Disease Control and Prevention (available at: http://www.cdc.gov/cancer/npcr/ accessed on March 3, 2008). The Surveillance, Epidemiology, and End Results Program (SEER) is administered through the National Cancer Institute (available at: http://seer.cancer.gov/ accessed on March 3, 2008). Central cancer registries also submit data to the North American Association of Central Cancer Registries, which is an association of population-based cancer registries.

Download figure to PowerPoint

We used cancer mortality data obtained from death certificates that contained demographic information and cause of death throughout the United States and that were coded according to the version of the ICD-O that was in use at the time of death. These data are reported to state vital statistics offices and consolidated into a national database by the CDC through the National Vital Statistics System.18 The underlying cause of cancer death is coded to the primary cancer site according to the version of the International Classification of Diseases (ICD) in use at the time of death and is grouped for maximum comparability among ICD versions.13, 14, 19 The US Standard Certificate of Death, which is used as a model by the state, was revised in 2003.20 This report includes data from 4 states (California, Idaho, Montana, and New York), which implemented the 2003 revision of the US Standard Certificate of Death in 2003. For the remaining 46 States and the District of Columbia that collected and reported death data in 2003, the data were based on the 1989 revision of the US Standard Certificate of Death. The 2003 revision of the US Standard Certificate of Death allows the reporting of more than 1 race (multiple races).20

Data Sources: Databases Used in This Supplement

Cancer incidence data were included in this Supplement if the cancer registry met the following publication criteria for the United States Cancer Statistics (USCS) report for all years from 1998 through 2003: Case ascertainment was at least 90% of expected cases (with the expected cases estimated by using methods developed by NAACCR), ≥97% of cases passed a standard set of computerized edits, ≤5% of cases were reported by death certificate only, ≤5% of cases were missing information on race, ≤3% of cases were missing information on sex, and ≤3% of cases were missing information on age.7, 21

Although NPCR and SEER registries currently (since 1998) cover 100% of the US population, only registries that meet USCS publication criteria for all 6 years were included in this analysis to ensure that high-quality data were used. NPCR and SEER data from 39 registries met the data quality criteria for inclusion in this report. Figure 3 shows a map of the cancer registries that are included in our database. These registries cover approximately 83% of the US population: 84% of whites, 74% of blacks, 90% of Asian/Pacific Islanders (APIs), and 91% of Hispanics. Regionally, 98% of the population in the Northeast and Midwest are covered, 63% of the South is covered, and 88% of the West is covered. Because SEER has been in existence since 1973, analyses of treatment, trends and survival, which require data over a longer period of time, were limited to SEER data only.

thumbnail image

Figure 3. States by US Census region and division (total population coverage, 83%). Population coverage by region: Northeast, 98%; Midwest, 98%; South, 63%; West, 88%. States that did not meet the inclusion criteria were not included because they did not meet standards for high-quality data collection for all years from 1998 through 2003 (see Havener, 200421). USCS indicates United States Cancer Statistics.

Download figure to PowerPoint

NPCR data for this Supplement were reported to the CDC as of January 31, 2006. SEER data were reported to the NCI as of November 2005 and were made available through the SEER Program limited-use data file that was released in April 2006.22 Data from states that are supported by both NPCR and SEER are presented as reported to the CDC as of January 2006 unless stated otherwise.7

Variation by race (white, black, and API) and Hispanic ethnicity were examined extensively for this Supplement. NPCR and SEER obtain information on race and Hispanic ethnicity from medical records. Identification of Hispanic ethnicity for cancer cases was augmented by a hierarchical algorithm that used race, birthplace, sex, maiden name, and surname.23 The CDC and other national partners have established a strategy to improve identification of American Indian/Alaska Native (AI/AN) cases; however, data on AI/ANs are not presented as a separate category in this Supplement, because such an identification strategy was not complete for all years in our dataset.24

Cancer death data for the years 1998 through 2003 are based on records of deaths that occurred from 1998 through 2003 for which the records were received as of February 28, 2005. Cancer deaths that were diagnosed before 1999 were recoded to ICD-O-3 categories. Because the 2003 revision of the US Standard Certificate of Death allows for the selection of multiple races, multiracial decedents were recoded to a single race (either white, black, AI/AN, or API) according to their combination of races, Hispanic origin, sex, and age indicated on the death certificate.25

The population denominator data for calculating cancer incidence and mortality rates were obtained from the 2000 US Census and modified by SEER for the purpose of improving the accuracy of rates for the population of Hawaii.26

Case Definition and Explanation of Potential Association With HPV

This Supplement highlights the 6 cancer sites (cervical, vulvar, vaginal, anal, penile, and oral cavity/oropharynx) that are considered to have sufficient evidence for HPV as a carcinogen (Table 1).27 According to Parkin and Bray, the strict definition of population attributable fraction needs to be modified when noncervical HPV-associated cancers are considered, because the prevalence of HPV infection among individuals in the control group (cancer-free) at the particular anatomic site currently is unknown.2, 28 The prevalence of HPV DNA detection varies considerably by type of assay and detection method. For the noncervical HPV-associated cancers, the percentage attributable fraction refers to the general percent of those cancers in which HPV DNA can be demonstrated in tumor cells, or HPV prevalence. For this Supplement, attributable fractions were based on the work by Parkin with an update on oral cavity and oropharyngeal cancers based on a systematic review by Kreimer (Table 1).2, 3 The attributable fractions may be considered by some to be a conservative estimate of attributable fraction (or HPV DNA prevalence) for many of the sites. Taking into account a lack of systematic reviews of HPV DNA prevalence in most of the noncervical cancers, the different methodologies for determining HPV DNA prevalence and the geographic variability in the HPV-type distribution of the cancers, we believed that using this conservative estimate was most appropriate. We realize that the attributable fraction may change with additional research on HPV detection methods and systematic reviews. Thus, when we describe the burden, we are not taking into account the attributable fraction for each site. Instead, we are reporting the burden of potentially HPV-associated cancers, which were defined by focusing on specific sites and specific histologies, and we refer to these as ‘HPV-associated.’ This article and others that describe the burden of HPV-associated cancers in this Supplement do not attempt to provide actual estimates of the attributable fraction of HPV in these cancers but provide basic information about cancers in sites that are believed to be primarily HPV-associated. The information about burden provided in this Supplement can be compared over time by using the standardized criteria provided—independent of any variation that may occur over time in the estimated attributable fraction.

Table 1. Estimated Percentage Attributable to Human Papillomavirus*
Cancer Site% Attributable to HPVReferenceAmong HPV-positive, % Attributable to HPV-16 and HPV-18Reference(s)
  • HPV indicates human papillomavirus.

  • *

    This table was adapted from Parkin & Bray 20062 with updates based on Kreimer 2005.3 See text for further discussion of HPV-attributable fractions.

Cervix100Parkin & Bray 2006270Munoz 200449
Vagina40Parkin & Bray 2006280Daling 200250
Vulva40Parkin & Bray 2006280Trimble 199651; Iwasawa 199752
Penis40Parkin & Bray 2006263Rubin 200153
Anus90Parkin & Bray 2006292Daling 200454; Frisch 199955
Oral cavity25Kreimer 2005395Kreimer 20053
Oropharynx35Kreimer 2005389Kreimer 20053

We identified 5 HPV-associated sites for females (cervix, vulva, vagina, anus, and oral cavity/oropharynx) and 3 sites for males (penis, anus, and oral cavity/oropharynx). Cases were grouped according to the ICD-O-3 site categories listed in Table 2. Specific HPV-associated subsites were identified for cancers of the oral cavity and oropharynx.29 To further identify those cancers most likely to be HPV-associated, we also limited analyses by ICD-O-3 histology code (Table 3). Cervical cancer was limited to carcinomas (ICD-O-3 histology codes 8010-8671 and 8940-8941).1, 30 In all other sites, SCCs are most likely to be associated with HPV; thus, HPV-associated cancers of the vulva, vagina, penis, anus, and oral cavity/oropharynx were defined as SCCs (ICD-O-3 histology codes 8050-8084 and 8120-8131).2 Analyses that were limited by histology (or that described the distribution of histology) were confined to tumors with microscopically confirmed histology (Fig. 4).

thumbnail image

Figure 4. Invasive cancers that were examined in the Assessing the Burden of HPV-Associated Cancers in the United States (ABHACUS) supplement: United States, 1998 through 2003. Data are from population-based cancer registries that participate in the National Program of Cancer Registries (NPCR) and/or the Surveillance, Epidemiology, and End Results (SEER) Program and meet high-quality data criteria. These registries cover approximately 83% of the US population. Rates are per 100,000 persons and are age-adjusted to the 2000 US standard population. ‘All histologies’ excludes International Classification of Diseases for Oncology, 3rd edition (ICD-O-3) histology codes 9050 (mesothelioma), 9140 (Kaposi sarcoma), and 9590-9989 (lymphomas and leukemias). Cervical cancers were limited to carcinomas only (ICD-O-3 histology codes 8010-8671 and 8940-8941). All other sites were limited to squamous cell carcinomas only (ICD-O-3 histology codes 8050-8084 and 8120-8131). Oral cavity and oropharyngeal cancers were limited to the subsites specified in Table 2.

Download figure to PowerPoint

Table 2. Definitions for Site Recode and Histology Codes
SiteICD-O-3 Site CodeICD-O-3 Histology Code*
  • ICD-O-3, International Classification of Diseases for Oncology, 3rd Edition; NOS, not otherwise specified; HPV, human papillomavirus.

  • *

    All carcinomas defined as ICD-O-3 histology codes 8010-8671, 8940-8941. Squamous cell carcinomas (SCCs) defined as ICD-O-3 histology codes 8050-8084, 8120-8131.

  • This article and others in the current supplement that examined National Program of Cancer Registries/Surveillance, Epidemiology, and End Results excluded code 8077/2 (intraepithelial neoplasia 3) for vaginal, vulvar, and anal cancers.

  • SCCs of the rectum are included. Because the rectum is made up of glandular cells and not squamous cells, we assumed that microscopically confirmed rectal SCCs were miscoded to the rectum or were overlapping anal lesions and treated these cancers like anal cancers (see Joseph 200736).

Cervix uteriC53All carcinomas (squamous cell, adenocarcinoma, adenosquamous/glassy cell, small cell neuroendocrine, other and unspecified)
 EndocervixC53.0
 ExocervixC53.1
 Overlapping lesion of cervix uteriC53.8 
 Cervix uteriC53.9 
VaginaC52Squamous cell carcinomas
 Vagina, NOSC52.9 
VulvaC51Squamous cell carcinomas
 Labium majusC51.0 
 Labium minusC51.1 
 ClitorisC51.2 
 Overlapping lesion of vulvaC51.8 
 Vulva, NOSC51.9 
Anus, anal canal, and anorectumC21Squamous cell carcinomas
 Anus, NOSC21.0 
 Anal canalC21.1 
 Cloacogenic zoneC21.2 
 Overlapping lesion of rectum, anus and anal canalC21.8 
 RectumC20.9 
PenisC60Squamous cell carcinomas
 Prepuce (foreskin)C60.0 
 Glans penisC60.1 
 Body of penisC60.2 
 Overlapping lesion of penisC60.8 
 Penis, NOSC60.9 
Base of tongue and lingual tonsil Squamous cell carcinomas
 Base of tongue, NOSC01.9 
 Lingual tonsilC02.4 
Tonsil (including Waldeyer ring) Squamous cell carcinomas
 Tonsillar fossaC09.0 
 Tonsillar pillarC09.1 
 Overlapping lesion of tonsilC09.8 
 Tonsil, NOSC09.9 
 Waldeyer ringC14.2 
Other oropharynx, potentially HPV-associated Squamous cell carcinomas
 Overlapping lesion of tongueC02.8 
 Lateral wall of oropharynxC10.2 
 Overlapping lesion of oropharynxC10.8 
 Oropharynx, NOSC10.9 
 Pharynx, NOSC14.0 
 Overlapping lesion of lip, oral cavity, and pharynxC14.8 
Table 3. General Histologic Classification of Invasive and In Situ Cancers Examined in the Current Supplement “Assessing the Burden of HPV-Associated Cancers in the United States”*
HistologyICD-O-3 Codes
  • ICD-O-3 indicates International Classification of Diseases for Oncology, 3rd Edition.

  • *

    This article and others in the current supplement that examined National Program of Cancer Registries/ Surveillance, Epidemiology, and End Results excluded code 8077/2 (intraepithelial neoplasia 3) for vaginal, vulvar, and anal cancers.

Carcinomas8010-8671, 8940-8941
 Squamous cell and transitional cell8050-8084, 8120-8131
  Basaloid and cloacogenic8123, 8124
  Keratinizing8071
  Nonkeratinizing8072, 8073
  Verrucous8051
 Adenocarcinomas8140-8149, 8160-8162, 8190-8221,8260-8337, 8350-8551, 8570-8576, 8940-8941
 Adenosquamous and glassy cell8560, 8015
 Small cell/neuroendocrine8013, 8041-8045, 8240-8246
 Other specified carcinomas8014, 8030-8040, 8046, 8090-8110, 8150-8157, 8170-8180, 8230-8239, 8247-8255, 8340-8347, 8561-8562, 8580-8671
 Unspecified carcinomas8010-8012, 8020-8022
NoncarcinomasAll remaining values

Some articles in this Supplement examine the burden of in situ cancer (behavior code of 2 in the NPCR and SEER databases). Vulvar, vaginal, and anal intraepithelial neoplasia lesions (specifically, vulvar intraepithelial neoplasia 3, vaginal intraepithelial neoplasia 3, and anal intraepithelial neoplasia 3) with an ICD-O-3 histology code of 8077 and behavior code of 2 are required to be reported by NPCR and SEER registries but are not collected uniformly; thus, they were excluded from all analyses.31 It is believed generally that these lesions are associated with HPV.32 We have chosen to refer to these lesions by using Arabic numerals in accordance with World Health Organization terminology (eg, cervical intraepithelial neoplasia is referred to as CIN-3 rather than CIN-III). The collection of penile intraepithelial neoplasia (PIN-3) has not been required by NPCR and SEER since 2000.31

Anal and rectal SCCs were considered to be HPV-associated cancers for the purpose of our analyses. Anal SCCs are associated strongly with HPV.33–36 The majority of rectal cancers are adenocarcinomas, which are not considered HPV-associated. True rectal SCCs are rare, but they generally may be HPV-associated; overlapping SCCs of the anus also may be misclassified as rectal SCCs.36, 37 These cancers were included in our analyses of HPV-associated anal cancers (Table 2).34, 38 After we limited the analyses to microscopically confirmed SCCs, only 1.9% of invasive rectal cancers and 2.9% of all in situ rectal cancers were considered HPV-associated, whereas 77.9% of invasive anal cancers and 65.5% of in situ anal cancers were considered HPV-associated.

Oral cavity and oropharyngeal sites that are considered HPV-associated were grouped into 3 major anatomic subsites: the tonsil, including the Waldeyer ring; the base of tongue and lingual tonsil; and other HPV-associated sites within the oropharynx (Table 2). These sites were identified as having the strongest correlation with HPV by the scientific writing group on oral cavity and oropharyngeal cancers on the basis of existing literature and expert advice.29

Statistical Analysis

Age-adjusted incidence and death rates were calculated per 100,000 persons unless specified otherwise. Rates were age-adjusted to the 2000 US standard population by the direct method using 19 age groups (ages <1 year, 1-4 years, 5-9 years, 10-14 years, 15-19 years, … ≥85 years).39 Cancer cases with unknown sex or age were excluded from all analyses.

Incidence and death rates and 95% confidence intervals were calculated in SEER*Stat (version 6.2.4), a statistical software package that was developed by the NCI.40 Confidence intervals were based on the Gamma method and used the modification detailed by Tiwari et al.41 Rates were calculated by age, race (white, black, and API), ethnicity (Hispanic or non-Hispanic), stage, and US Census region (Northeast, South, East or West) (Fig. 3). The race category labeled as ‘all races combined’ and the overall cancer rates include individuals of all races: white, black, AI/AN, API, other, and unknown. Other and unknown categories were not reported on separately, because denominator information was not available for these groups; thus, the sum of the individual race categories (white, black, and API) will not equal the ‘all races combined’ category. Hispanic ethnicity included individuals from all race categories.

Cancers were staged according to SEER Summary Stage 1977 (for cases diagnosed before 2001) and SEER Summary Stage 2000 (for cases diagnosed in 2001 or later). For some cancer sites, differences between the 2 staging schemes can result in inconsistent staging.42, 43 Coding for regional and distant stages of cancers of the vagina and some oral cavity and oropharyngeal subsites was not consistent between the 2 schemes; thus, we reported only early or late stage for vaginal and oral cavity/oropharyngeal cancers. Where early or late stage is reported, early stage includes localized stage, and late stage includes regional and distant stages. Certain articles in this Supplement also examine tumor grade, with cancer cells classified by the degree of microscopic abnormality and the likelihood of growth and metastasis.30

RESULTS

  1. Top of page
  2. Abstract
  3. Data Sources: Cancer Registry and Mortality Surveillance Systems
  4. RESULTS
  5. REFERENCES

This section is intended to provide a general overview of the distribution of these cancers in the context of all HPV-associated cancers. Comprehensive descriptions of each cancer can be found in individual articles in this Supplement.29, 36, 44–47

Table 4 displays age-adjusted cancer incidence rates for the invasive cancers included in this article by registry. In total, there were 149,507 cases of invasive HPV-associated cancer from 1998 through 2003. Cervical carcinomas, as expected, were the most frequent cancers examined in our study, with an average of 10,846 cases per year, followed by oral cavity and oropharyngeal SCCs, with an average of 7360 cases per year. The averages were 3018 cases of anal and rectal SCCs per year and 2266 vulvar SCCs per year. Penile and vaginal cancers were rare, with average annual counts of 828 and 601 per year, respectively. The South Atlantic division had the highest rates of cervical, anal, and oral cavity/oropharyngeal cancers, whereas the West South Central division had the highest rates of vaginal and penile cancers. The East South Central division had the highest rate of vulvar cancer. Figure 5 displays age-adjusted cancer incidence rates for invasive cancers by Census division.

thumbnail image

Figure 5. Rates of invasive human papillomavirus-associated cancers by US Census Division. Only carcinomas are included for cervical cancers. Only squamous cell carcinomas (SCCs) are included for vulvar, vaginal, penile, anal and oral cavity/oropharyngeal cancers. All histologies were confirmed microscopically. Data are from population-based cancer registries that participate in the National Program of Cancer Registries and/or the Surveillance, Epidemiology, and End Results Program and meet high-quality data criteria. These registries cover approximately 83% of the US population. Rates are per 100,000 persons and are age-adjusted to the 2000 US standard population. Note that the rate scale varies by cancer site. These maps were developed by James Cucinelli (IMS, Inc.) and Dave Stinchcomb (National Cancer Institute) based on the micromaps design.

Download figure to PowerPoint

Table 4. Average Annual Incidence Counts and Rates of Invasive Cancers Associated With Human Papillomavirus by Registry: United States, 1998-2003*
RegistryCervixVaginaVulvaAnusPenisOral Cavity and OropharynxAverage Annual Total
CountRateCountRateCountRateCountRateCountRateCountRateCount
  • *

    Only carcinomas are included for cervical cancers. Only squamous cell carcinomas (SCCs) are included for vulvar, vaginal, penile, anal and oral cavity/oropharyngeal cancers. All histologies were microscopically confirmed.

  • Data are from population-based cancer registries that participate in the National Program of Cancer Registries and/or the Surveillance, Epidemiology, and End Results Program and meet high-quality data criteria. These registries cover approximately 83% of the US population. Rates are per 100,000 persons and are age-adjusted to the 2000 US standard population.

  • Anal cancers include SCCs coded to the rectum. Oral cavity and oropharyngeal cancers are limited to the subsites specified in Table 2.

  • §

    Indicates that the cell was suppressed because the average annual count was <3 during the 6-year period.

Alaska227.8§§52.081.7§§183.855
Alabama2179.1140.5502.0511.1140.71513.3496
Arkansas14510.390.6241.6391.4151.2993.5331
California15529.2720.42321.44391.4900.79193.03304
Colorado1547.070.3271.3481.2110.71032.6349
Connecticut1347.090.4442.0391.1161.01123.1354
District of Columbia3711.831.051.6132.4§§295.1§
Delaware388.930.692.081.0§§283.4§
Florida90710.3430.41711.63231.7690.87994.32311
Hawaii599.2§§60.990.7§§312.4108
Idaho416.630.481.3141.140.8332.7103
Illinois64010.0300.41211.81461.2410.83893.21366
Indiana2698.6170.5631.9761.3220.81933.2640
Iowa1238.290.4412.3321.0130.9782.5295
Kansas1128.250.3241.5331.270.6712.7251
Kentucky23010.7120.5472.1551.3241.31383.3506
Louisiana23610.4150.6532.3591.4171.01523.5533
Massachusetts2256.4170.4711.8771.2260.92093.2624
Maine547.550.6192.4221.571.1553.8161
Michigan4208.1300.51102.01111.1350.83173.21022
Minnesota1676.6120.5521.9440.9211.01262.6421
Missouri2669.0130.4621.9721.3210.91943.3628
Montana377.9§§71.3111.151.1303.1§
Nebraska698.130.3171.6201.181.1422.4159
New Jersey4439.6190.4891.81011.1320.92603.0945
New Mexico737.950.5131.4221.250.7362.0154
New York9258.9490.41901.72651.4670.85352.82031
Ohio4938.2300.51301.91381.2340.73432.91168
Oklahoma1709.7100.5361.9501.4140.91113.2390
Oregon1377.790.4361.8561.6100.61183.3366
Pennsylvania5688.5390.51571.91581.2450.84303.21396
Rhode Island427.330.4162.4161.450.9312.8111
South Carolina2099.8120.5442.0471.2150.91563.8482
Texas101810.0550.61441.52401.3781.05513.02086
Utah596.230.3121.4181.140.5321.9128
Vermont288.430.772.050.831.0182.764
Washington2137.0120.4531.7761.3160.61843.2552
Wisconsin2117.7130.4531.7500.9170.71703.1513
West Virginia11010.980.6221.9311.5111.1693.3250
Average annual total10,8468.96010.522661.730181.38280.873603.124,918
No. for 1998-200365,074 3604 13,597 18,105 4967 44,160 149,507

Rate and percentage distributions of invasive cancers associated with HPV by sex, cancer site, age, race, ethnicity, disease stage, and region are shown in Table 5. There were 104,097 cases of HPV-associated cancers among women during 1998 through 2003. The median age at diagnosis for cervical carcinoma was 47 years. Other invasive HPV-associated cancers tended to be diagnosed later, with a median age >60 years at diagnosis. Approximately 50% of vaginal and vulvar SCCs were diagnosed among women aged ≥70 years. Black women had higher rates of invasive cervical carcinoma, and vaginal SCCs, and oral cavity/oropharyngeal SCCs, whereas white women had higher rates of vulvar and anal SCCs. Hispanic women had higher rates of cervical cancer than non-Hispanic women, whereas non-Hispanic women had higher rates of oral cavity and oropharyngeal cancers. All HPV-associated cancers among women were diagnosed most often at the localized stage, with the exception of oral cavity and oropharyngeal SCCs, which were diagnosed more frequently at the regional stage. The South had the highest rates of cervical, vaginal, anal, and oral cavity/oropharyngeal cancers, whereas the Midwest had the highest rate of vulvar cancer.

Table 5. Invasive Cancers Associated With Human Papillomavirus by Selected Characteristics: United States, 1998-2003*
FeatureFemaleMale
CervixVulvaVaginaAnusOral Cavity and OropharynxPenisAnusOral Cavity and Oropharynx
Rate%Rate%Rate%Rate%Rate%Rate%Rate%Rate%
  • API indicates Asian/Pacific Islander.

  • *

    Data are from population-based cancer registries that participate in the National Program of Cancer Registries and/or the Surveillance, Epidemiology, and End Results (SEER) Program and meet high-quality data criteria (see Table 4 for a list of registries). These registries cover approximately 83% of the population for the period studied.

  • The data represent incidence rates and % distribution of cases unless otherwise specified. Rates are per 100,000 persons and are age-adjusted to the 2000 US standard population. Hispanic origin is not mutually exclusive from race categories (white, black, API). Rates could not be calculated for individuals of other or unknown race/ethnicity; thus, percentage distributions for race categories do not total 100%. Only microscopically confirmed cervical carcinomas and squamous cell carcinomas (SCCs) for other sites were examined.

  • SEER Summary Stage 1977 was used for cancers diagnosed from 1998 through 2000, and SEER Summary Stage 2000 was used for cancers diagnosed from 2001 through 2003. Stage for vagina and some oral cavity and oropharyngeal subsites are not considered comparable between these staging schemes, so regional and distant stage were combined to make the 2 schemes comparable.

  • §

    Regional and distant stage have been combined for cancers of the vagina and oral cavity/oropharynx.

Overall8.91001.71000.51001.51001.31000.81001.01005.2100
Median age, y4769706264685758
Age, y                
 <301.46.3<0.10.7<0.10.5<0.10.3<0.10.5<0.10.4<0.10.6<0.10.2
 30-3913.522.10.75.50.13.40.43.70.32.70.23.70.69.70.72.0
 40-4915.826.31.814.20.410.51.917.81.212.40.59.61.423.35.818.3
 50-5914.518.02.514.60.715.63.322.82.923.31.116.91.922.614.833.6
 60-6914.812.53.715.11.319.34.320.14.826.02.524.42.619.618.025.6
 ≥7012.314.88.449.92.350.75.235.34.735.34.544.93.124.213.120.3
Race                
 White8.479.11.890.70.482.21.689.91.387.10.888.31.085.65.186.5
 Black12.614.51.36.90.714.01.37.81.510.50.87.81.211.46.811.1
 API8.33.90.40.70.32.00.41.00.51.30.41.40.20.71.71.1
Ethnicity                
 Non-Hispanic8.484.21.895.00.490.91.592.81.496.00.887.31.093.45.394.8
 Hispanic14.215.81.35.00.69.11.57.20.74.01.312.70.86.63.65.2
Stage                
 Localized4.752.31.162.40.244.40.851.20.322.40.562.40.553.70.815.3
 Regional§2.831.50.528.20.242.00.425.60.970.20.227.70.325.14.077.9
 Distant0.89.10.13.40.18.20.03.20.16.5
 Unstaged0.67.10.15.90.113.60.215.00.17.40.16.70.214.70.46.8
Region               15.3
 Northeast8.422.31.826.20.423.71.421.91.323.60.924.21.023.84.922.0
 Midwest8.525.51.929.60.426.91.424.91.326.00.826.50.822.15.026.1
 South10.130.61.726.60.530.41.730.91.530.00.931.41.129.45.931.3
 West8.521.61.417.50.419.01.622.31.320.30.718.01.124.74.720.5

There were 45,410 cases of HPV-associated cancers among men from 1998 through 2003. Among men, those with invasive anal and oral cavity/oropharyngeal SCCs were younger at diagnosis (median ages, 57 years and 58 years, respectively) than men with invasive penile SCCs (median age at diagnosis, 68 years). API men had lower rates of all invasive HPV-associated cancers, whereas black men had higher rates of invasive anal and oral cavity/oropharyngeal SCCs. Hispanic men had higher rates of invasive penile SCC, and non-Hispanic men had higher rates of invasive anal and oral cavity/oropharyngeal SCCs. Invasive penile and anal SCCs in men were diagnosed most often at the localized stage. Invasive oral cavity and oropharyngeal cancers were most likely to be diagnosed at the regional stage. The rate of invasive penile SCC was lowest for men in the West, whereas the rate of invasive anal SCC was lowest in the Midwest. The rates of invasive oral cavity and oropharyngeal SCCs among men were highest in the South.

Among cancers for which both women and men were at risk, anal cancers were more common among women, whereas men had higher rates of oral and oropharyngeal cancers. Men tended to be diagnosed with invasive anal and oral cavity/oropharyngeal SCCs at younger ages than women. White women had the highest rate of invasive anal SCC, whereas blacks had the highest rate among men.

Table 6 examines in situ vulvar, vaginal, penile, anal, and oral cavity/oropharyngeal SCCs by age, race, ethnicity, and region. There were 15,593 noncervical in situ cancers that were considered to be HPV-associated from 1998 through 2003; 11,379 of those cancers were diagnosed in women, and 4214 were diagnosed in men. Generally, the patterns were similar to those observed for invasive disease.

Table 6. In Situ Cancers Associated With Human Papillomavirus by Selected Characteristics: United States, 1998-2003*
FeatureFemaleMale
VulvaVaginaAnusOral Cavity and OropharynxPenisAnusOral Cavity and Oropharynx
Rate%Rate%Rate%Rate%Rate%Rate%Rate%
  • API indicates Asian/Pacific Islander.

  • *

    Data are from population-based cancer registries that participate in the National Program of Cancer Registries (NPCR) and/or the Surveillance, Epidemiology, and End Results (SEER) Program and meet high-quality data criteria (see Table 4 for a list of registries). These registries cover approximately 83% of the population for the period studied.

  • The data represent incidence rates and % distribution of cases unless otherwise specified. Rates are per 100,000 persons and are age-adjusted to the 2000 US standard population. Hispanic origin is not mutually exclusive from race categories (white, black, API). Rates could not be calculated for individuals of other or unknown race/ethnicity; thus, the percentage distribution for race categories does not total 100%. In situ cervical cancer is no longer reportable and, thus, was not included. Only microscopically confirmed squamous cell carcinomas (SCCs) were examined.

  • ‡This article and others in the current supplement that examined National Program of Cancer Registries/Surveillance, Epidemiology, and End Results excluded code 8077/2 (intraepithelial neoplasia 3) for in situ vaginal, vulvar, and anal cancers.

  • §

    Indicates that the cell was suppressed because of a count <16 during the 6-year period.

Overall1.21000.11000.2100<0.11000.41000.21000.1100
Median age, y49595365634560
Age, y              
 <300.25.6<0.14.0§§§0.7<0.13.40.03.9§0.3
 30-391.417.00.18.70.112.0§4.30.27.80.429.7§1.4
 40-492.428.40.219.80.327.4<0.111.40.414.40.432.50.114.9
 50-592.422.10.219.30.422.5<0.116.40.617.60.317.60.130.6
 60-692.112.70.318.60.415.80.132.11.222.10.28.80.229.5
 ≥701.714.10.429.60.321.10.135.01.734.60.27.60.223.4
Race              
 White1.386.60.183.20.287.0<0.183.60.486.90.281.00.186.2
 Black0.97.90.19.00.18.5<0.112.90.35.80.313.80.110.7
 API0.10.5§1.3§§§2.10.11.2§§§1.4
Ethnicity              
 Non-Hispanic1.3195.30.192.90.294.7<0.197.90.493.50.290.00.196.7
 Hispanic0.614.70.17.10.15.3§2.10.36.50.210.0§3.3
Region              
 Northeast0.917.10.119.20.223.4<0.121.40.318.70.221.30.121.5
 Midwest1.430.20.130.50.224.7<0.123.60.427.60.118.30.128.4
 South1.533.50.233.00.227.3<0.131.40.424.90.229.90.128.9
 West1.019.20.117.40.224.6<0.123.60.528.80.230.40.121.2

Data Limitations

Cancer registry data do not contain information on the presence of HPV in tumor tissue. To minimize this limitation, we chose sites with an established HPV association and limited our analyses by histology and microscopic confirmation. Case-level data on other risk factors for these cancers, such as smoking and high parity, also are not available from cancer registries. We excluded registries that did not meet USCS standards for data quality and timeliness for any year during 1998 through 2003; thus, these data do not cover the entire population of the United States. A lower proportion of the population was included from the South (63%) than from any other US Census region because of the exclusion of more registries from this region. However, an analysis of cervical cancer that included more states from the South but was limited to more recent years revealed that the rates in this region remained significantly increased compared with other regions.45 Thus, we believe that differences between the South and other regions are representative and are not an artifact of lower population coverage in the South. There are several limitations concerning the collection of in situ tumors that may have influenced our analyses. Although NPCR and SEER require reporting of in situ tumors, the quality of the data is not as consistent as the quality of the data for invasive cancers.31

In summary, this Supplement represents our first attempt to assess the overall burden of HPV-associated cancers in the United States. The available data cover the majority of the US population. This comprehensive analysis sets the stage for monitoring the impact of the HPV vaccine and potential temporal and geographic changes in HPV-associated disease burden. By using population-based cancer registries, the ABHACUS Supplement has achieved its main purposes: assessing the current (prevaccine) burden of HPV-associated cancers and providing a baseline for monitoring future trends in these cancers. Histology categories are described comprehensively and are based on current knowledge. In addition, the focus on histologic-specific analyses and rare cancer sites should benefit planning for future etiological and clinical studies, as well as vaccine interventions, by providing a critical baseline assessment of the population burden of HPV-associated malignancy. It is our hope that, with current population-based cancer registries covering 100% of the US population since 1998, we will be in a position to monitor changes in the burden of in situ and invasive HPV-associated cancers with more accuracy and precision.21, 48

REFERENCES

  1. Top of page
  2. Abstract
  3. Data Sources: Cancer Registry and Mortality Surveillance Systems
  4. RESULTS
  5. REFERENCES
  • 1
    Walboomers JMM,Jacobs MV,Manos MM, et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol. 1999; 189: 1219.
  • 2
    Parkin DM,Bray F. Chapter 2: the burden of HPV-related cancers. Vaccine. 2006; 24( suppl 3): S11S25.
  • 3
    Kreimer AR,Clifford GM,Boyle P,Franceschi S. Human papillomavirus types in head and neck squamous cell carcinomas worldwide: a systematic review. Cancer Epidemiol Biomarkers Prev. 2005; 14: 467475.
  • 4
    Joura EA,Leodolter S,Hernandez-Avila M, et al. Efficacy of a quadrivalent prophylactic human papillomavirus (types 6, 11, 16, and 18) L1 virus-like-particle vaccine against high-grade vulval and vaginal lesions: a combined analysis of 3 randomised clinical trials. Lancet. 2007; 369: 16931702.
  • 5
    Villa LL,Costa RL,Petta CA, et al. High sustained efficacy of a prophylactic quadrivalent human papillomavirus types 6/11/16/18 L1 virus-like particle vaccine through 5 years of follow-up. Br J Cancer. 2006; 95: 14591466.
  • 6
    National Institutes of Health. ClinicalTrials.gov. Bethesda, Md: National Institutes of Health, National Library of Medicine, Department of Health and Human Services; 2008. Available at: http://clinicaltrials.gov. Accessed January 7, 2008.
  • 7
    US Cancer Statistics Working Group. United States Cancer Statistics: 2003 Incidence and Mortality. Atlanta, Ga: Centers for Disease Control and Prevention; 2005. Available at: http://www.cdc.gov/cancer/npcr/uscs/. Accessed October 23, 2007.
  • 8
    Hankey BF,Ries L,Edwards BK. The Surveillance, Epidemiology, and End Results Program: a national resource. Cancer Epidemiol Biomarkers Prev. 1999; 8: 11171121.
  • 9
    Thoburn KK,German RR,Lewis M,Nichols PJ,Ahmed F,Jackson-Thompson J. Case completeness and data accuracy in the Centers for Disease Control and Prevention's National Program of Cancer Registries. Cancer. 2007; 109: 16071616.
  • 10
    US Congress.Cancer Registries Amendment Act, Public Law No. 102-515, Stat. 3312. Congressional Record, 1992, volume 128. Washington, DC: US Department of Health and Human Services, Public Health Service; 1992.
  • 11
    Wingo PA,Jamison PM,Hiatt RA, et al. Building the infrastructure for nationwide cancer surveillance and control-a comparison between the National Program of Cancer Registries (NPCR) and the Surveillance, Epidemiology, and End Results (SEER) Program (United States). Cancer Causes Control. 2003; 14: 175193.
  • 12
    Surveillance, Epidemiology, and End Results (SEER) Program. The SEER Program Coding and Staging Manual 2004, Revision 1. NIH Publication No. 04-5581. Bethesda, Md: National Cancer Institute; 2007.
  • 13
    International Classification of Diseases for Oncology, 3rd ed. Geneva, Switzerland: World Health Organization; 2000.
  • 14
    International Classification of Diseases for Oncology, 2nd ed. Geneva, Switzerland: World Health Organization; 1990.
  • 15
    US Cancer Statistics Working Group. United States Cancer Statistics: 2003 Incidence and Mortality. Atlanta, Ga: Centers for Disease Control and Prevention; 2006. Available at: http://www.cdc.gov/cancer/npcr/uscs/. Accessed October 23, 2007.
  • 16
    National Cancer Institute. Conversion Programs, ICD-O-2 to 3 and ICD-O-3 to 2. Bethesda, Md: Surveillance, Epidemiology, and End Results (SEER) Program; 2004. Available at: http://seer.cancer.gov/tools/conversion/. Accessed October 11, 2007.
  • 17
    National Cancer Registrars Association (NCRA). Central Cancer Registries: Design, Management and Use, 2nd ed. Dubuque, Iowa: Kendall/Hunt Publishing Company; 2007.
  • 18
    National Center for Health Statistics (NCHS). National Vital Statistics System. Atlanta, Ga: Centers for Disease Control and Prevention, National Center for Health Statistics; 2007. Available at: http://www.cdc.gov/nchs/nvss.htm. Accessed October 23, 2007.
  • 19
    National Cancer Institute. SEER Cause of Death Recode. Bethesda, Md: National Cancer Institute, Surveillance, Epidemiology, and End Results Program; 2008. Available at: http://seer.cancer.gov/codrecode/. Accessed February 8, 2008.
  • 20
    National Center for Health Statistics (NCHS). 2003 Revision of the US Standard Certificate of Death. Atlanta, Ga: NCHS; 2003. Available at: http://www.cdc.gov/nchs/data/dvs/DEATH11-03final-acc.pdf. Accessed March 25, 2008.
  • 21
    HavenerL, ed. Standards for Cancer Registries, Vol III: Standards for Completeness, Quality, Analysis, and Management of Data. Springfield, Ill: North American Association of Central Cancer Registries; 2004.
  • 22
    National Cancer Institute. SEER Data, 1973-2004. Bethesda, Md: National Cancer Institute; 2008. Available at: http://seer.cancer.gov/publicdata/. Accessed March 25, 2008.
  • 23
    NAACCR Latino Research Work Group. NAACCR guideline for enhancing Hispanic-Latino identification: revised NAACCR Hispanic/Latino identification algorithm (NHIA version 2). Springfield, Ill: North American Association of Central Cancer Registries; 2005.
  • 24
    Espey DK,Wu X,Swan J, et al. Annual report to the nation on the status of cancer, 1975-2004, featuring cancer in American Indians and Alaska Natives. Cancer. 2007; 110: 21192152.
  • 25
    National Center for Health Statistics (NCHS). Deaths: FinalData for 2003. Atlanta, Ga: NCHS; 2007. Available at: http://www.cdc.gov/nchs/products/pubs/pubd/hestats/finaldeaths03/finaldeaths03.htm#1. Accessed March 25, 2008.
  • 26
    Surveillance Epidemiology and End Results. US Population Data-1969-2005. Bethesda, Md: National Cancer Institute; 2008. Available at: http://seer.cancer.gov/popdata/. Accessed March 25, 2008.
  • 27
    IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Human papillomaviruses. IARC Monogr Eval Carcinog Risks Hum. 2007; 90: 1636.
  • 28
    Parkin DM. The global health burden of infection-associated cancers in the year 2002. Int J Cancer. 2006; 118: 30303044.
  • 29
    Ryerson AB,Peters ES,Coughlin SS, et al. Burden of potentially human papillomavirus-associated cancers of the oropharynx and oral cavity in the United States, 1998-2003. Cancer. 2008; 113( 10 suppl); 29012909.
  • 30
    Berg JW. Morphologic classification of human cancer. In: SchottenfeldD,FraumeniJF, eds. Cancer Epidemiology and Prevention,2nd ed. New York, NY: Oxford University Press; 1996: 2844.
  • 31
    Saraiya M,Goodman MT,Datta SD,Chen VW,Wingo PA. Cancer registries and monitoring the impact of prophylactic human papillomavirus vaccines: the potential role [commentary]. Cancer. 2008; 113( 10 suppl); 30473057.
  • 32
    Hampl M,Sarajuuri H,Wetzensen N,Bender HG,Kueppers V. Effect of human papillomavirus vaccines on vulvar, vaginal, and anal intraepithelial lesions and vulvar cancer. Obstet Gynecol. 2006; 108: 13611368.
  • 33
    Frisch M,Glimelius B,van den Brule AJ, et al. Sexually transmitted infection as a cause of anal cancer. N Engl J Med. 1997; 337: 13501358.
  • 34
    Frisch M. On the etiology of anal squamous carcinoma. Danish Med Bull. 2002; 49: 194209.
  • 35
    Melbye M,Frisch M. The role of human papillomaviruses in anogenital cancers. Semin Cancer Biol. 1998; 8: 307313.
  • 36
    Joseph DA,Miller JW,Wu X, et al. Understanding the burden of human papillomavirus-associated anal cancers in the United States. Cancer. 2008; 113( 10 suppl); 28922900.
  • 37
    Kong C,Welton ML,Longacre T. Role of human papillomavirus in squamous cell metaplasia-dysplasia-carcinoma of the rectum. Am J Surg Pathol. 2007; 31: 919925.
  • 38
    Johnson LG,Madeleine MM,Newcomer LM,Schwartz SM,Daling JR. Anal cancer incidence and survival: the Surveillance, Epidemiology, and End Results experience, 1973-2000. Cancer. 2004; 101: 281288.
  • 39
    Surveillance Epidemiology, and End Results Program. 2000 US Standard Population vs Standard Million. Bethesda, Md: National Cancer Institute; 2007. Available at: http://seer.cancer.gov/stdpopulations/single_age.html. Accessed October 23, 2007.
  • 40
    Surveillance Research Program, National Cancer Institute. SEER*Stat Software. Bethesda, Md: Surveillance Research Program, National Cancer Institute; 2007. Available at: http://seer.cancer.gov/seerstat/. Accessed March 25, 2008.
  • 41
    Tiwari RC,Clegg LX,Zou Z. Efficient interval estimation for age-adjusted cancer rates. Stat Methods Med Res. 2006; 15: 547569.
  • 42
    Howe HL,Jamison M,Havener L,Chen VW,Ries L. Site-specific comparison of Summary Stage 1977 and Summary Stage 2000 coding. Springfield, Ill: North America Association of Central Cancer Registries; 2007. Available at: http://www.naaccr.org/index.asp?Col_SectionKey=11&Col_ContentID=397 Accessed on March 25, 2008.
  • 43
    Phillips J. Summary Stage: Data Effects of the Changes in 2000. Springfield, Ill: North American Association of Central Cancer Registries; 2003.
  • 44
    Wu X,Matanoski G,Chen VW, et al. Descriptive epidemiology of vaginal cancer incidence and survival by race, ethnicity, and age in the United States. Cancer. 2008; 113( 10 suppl): 28732882.
  • 45
    Watson M,Saraiya M,Benard V, et al. Burden of cervical cancer in the United States, 1998-2003. Cancer. 2008; 113( 10 suppl): 28552864.
  • 46
    Saraiya M,Watson M,Wu X, et al. Incidence of in situ and invasive vulvar cancer in the United States, 1998-2003. Cancer. 2008; 113( 10 suppl): 28652872.
  • 47
    Hernandez BY,Barnholtz-Sloan J,German RR, et al. Burden of penile cancer in the United States. Cancer. 2008; 113( 10 suppl): 28832891.
  • 48
    National Program of Cancer Registries, Centers for Disease Control and Prevention. Ten Years of Progress: The National Program of Cancer Registries: CDC's Progress in Building a National Cancer Surveillance Network. Atlanta, Ga: Centers for Disease Control and Prevention; 2007. Available at: http://www.cdc.gov/cancer/npcr/anniversary/progress.htm. Accessed March 25, 2008.
  • 49
    Munoz N,Bosch FX,Castellsague X, et al. Against which human papillomavirus types shall we vaccinate and screen? The international perspective. Int J Cancer. 2004; 111: 278285.
  • 50
    Daling JR,Madeleine MM,Schwartz SM, et al. A population-based study of squamous cell vaginal cancer: HPV and cofactors. Gynecol Oncol. 2002; 84: 263270.
  • 51
    Trimble CL,Hildesheim A,Brinton LA,Shah KV,Kurman RJ. Heterogeneous etiology of squamous carcinoma of the vulva. Obstet Gynecol. 1996; 87: 5964.
  • 52
    Iwasawa A,Nieminen P,Lehtinen M,Paavonen J. Human papillomavirus in squamous cell carcinoma of the vulva by polymerase chain reaction. Obstet Gynecol. 1997; 89: 8184.
  • 53
    Rubin MA,Kleter B,Zhou M, et al. Detection and typing of human papillomavirus DNA in penile carcinoma: evidence for multiple independent pathways of penile carcinogenesis. Am J Pathol. 2001; 159: 12111218.
  • 54
    Daling JR,Madeleine MM,Johnson LG, et al. Human papillomavirus, smoking, and sexual practices in the etiology of anal cancer. Cancer. 2004; 101: 270280.
  • 55
    Frisch M,Fenger C,Van den Brule AJC, et al. Variants of squamous cell carcinoma of the anal canal and perianal skin and their relation to human papillomaviruses. Cancer Res. 1999; 59: 753757.