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ORIGINAL RESEARCH |
From the 1Department of Obstetrics, Gynecology & Women’s Health, Division of Gynecologic Oncology, 2Division of Health Services Research and Policy, 3Department of Surgery, Division of Colorectal Surgery, and 4University of Minnesota Cancer Center, University of Minnesota, Minneapolis, Minnesota.
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ABSTRACT |
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METHODS: We used the Surveillance Epidemiology and End Results database to assess trends in the incidence of vulvar cancer over a 28-year period (1973 through 2000) and determined whether there had been a change in incidence over time. Information collected included patient characteristics, primary tumor site, tumor grade, and follow-up for vital status. We calculated the incidence rates by decade of age, used 
2 tests to compare demographic characteristics, and tested for trends in incidence over time.
RESULTS: A total of 13,176 in situ and invasive vulvar carcinomas were identified; 57% of the women were diagnosed with in situ, 44% with invasive disease. Vulvar carcinoma in situ increased 411% from 1973 to 2000. Invasive vulvar cancer increased 20% during the same period. The incidence rates for in situ and invasive vulvar carcinomas are distributed differently across the age groups. In situ carcinoma incidence increases until the age of 40–49 years and then decreases, whereas invasive vulvar cancer risk increases as a woman ages, increasing more quickly after 50 years of age.
CONCLUSION: The incidence of in situ vulvar carcinoma is increasing. The incidence of invasive vulvar cancer is also increasing but at a much lower rate.
LEVEL OF EVIDENCE: III
Vulvar cancer makes up 3% to 5% of all female genital cancers. The definition of vulvar cancer frequently includes both vulvar cancer and carcinoma in situ, also called vulvar intraepithelial neoplasia III. Sturgeon et al2 identified an increasing incidence of vulvar carcinoma in situ more than a decade ago and postulated that this would result in an increase in invasive vulvar cancer.
The association between in situ vulvar carcinoma and the human papillomavirus (HPV) is established,3,4 with HPV DNA identified in 72% of vulvar intraepithelial neoplasia lesions.3 In contrast, HPV infection and invasive vulvar cancer appear to be less strongly correlated. Studies show HPV associated with vulvar cancer in 14–60% of cases, with most studies showing approximately 40%. The different association between HPV infection in invasive and in situ disease is in marked contrast to squamous cell carcinoma of the cervix, where the prevalence of HPV is close to 100% for invasive disease. Although it has been shown that HPV-related cervical dysplasia can progress to cervical cancer,10,11 the progression of vulvar carcinoma in situ to vulvar cancer has been suggested but not confirmed.
Human papillomavirus is one of the most common sexually transmitted infections in the United States.18 It is estimated that more than 50% of sexually active people will acquire genital HPV and that 80% of women will have acquired genital HPV by age 50 years. Given this trend, we would expect to see a rise in both in situ and invasive vulvar carcinoma if, in fact, both are causally related to HPV infection.
We undertook this analysis to characterize trends in the incidence of vulvar carcinoma in situ and vulvar cancer with the intent of identifying possible mechanisms underlying the trends.
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MATERIALS AND METHODS |
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ABSTRACTMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Our population consists of 13,176 patients with vulvar carcinomas, in situ and invasive. Women were excluded if they were diagnosed with any other cancer before developing vulvar cancer. We divided the cohort into 2 age cohorts of women aged 0–49 years and women older than 50 years of age at diagnosis, roughly representing premenopausal and postmenopausal age groups. The older than 50 years cohort contained 7,579 (57.2%) women; the remaining 5,597 (42.5%) were younger than 50 years old.
We compiled a comparison cohort of women diagnosed with squamous cell cervical carcinoma. Cervical carcinoma was chosen as the comparison group, given its similarity to vulvar carcinoma in being HPV-related. Of the 110,806 women included, 81,892 (74%) were diagnosed with in situ disease, and 28,914 (26%) with invasive cancer. All in situ cases are from years before 1996, when SEER ceased reporting in situ cervical carcinoma.22
Incidence rates (per 100,000 female population) per year were calculated using standard SEER methodology and the SEER*Stat (National Cancer Institute, http://www.seer.cancer.gov/publicdata/access.html) and SAS (SAS Institute Inc., Cary, NC) software for vulvar carcinoma from 1973 through 2000. We evaluated rates of in situ and invasive vulvar carcinomas by age to evaluate differences in incidence over the life-span and for 3 periods: 1973–1981, 1982–1991, and 1992–2000. We used 2 tests to compare demographic characteristics of incident cancer cases between women aged 0–49 years and women aged 50 years and older. We determined whether rates changed over time using the Cochran-Armitage trend test with 1 degree of freedom for each stage.23
The study used de-identified public-use data obtained from the SEER program and are considered human subjects–exempt. Institutional review board approval was not applied for at the University of Minnesota. However, the institutional review board agreed that the activities described are exempt from review under Federal Guidelines 45CF part 46.101 (b) category #4.
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RESULTS |
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The incidence rates for in situ and invasive vulvar carcinomas are distributed differently across the age groups (Fig. 1 and 2). Similar to the pattern seen in our comparison cohort of women diagnosed with in situ cervical carcinomas (Fig. 1), in situ vulvar carcinoma incidence has a peak and then declines. This peak, however, is approximately 20 years later than the in situ cervical peak.
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The incidence of in situ vulvar carcinoma and invasive carcinoma increased over the period 1973–2000 (Table 2, Fig. 3 and 4). The incidence of in situ disease increased 411%, from 0.56 cases per 100,000 women in 1973 to 2.86 per 100,000 women (P < .001) in 2000 (Table 2). In contrast, invasive vulvar cancer experienced only a modest 20% increase from 1973 to 2000, with little apparent change in age-specific rates. In 1973, there were 1.8 cases per 100,000, and in 2000 the rate increased minimally to 2.2 cases per 100,000 women (P < .001).
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DISCUSSION |
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Despite the increase of in situ vulvar carcinoma, we have observed relatively little change in the incidence of invasive vulvar cancer, particularly in women younger than 50 years. If HPV-induced in situ vulvar carcinoma progressed reliably to vulvar cancer, as in cervical cancer, we would expect to see a peak in the incidence of vulvar cancer approximately 5 to 20 years after the peak of in situ disease, as seen in cervical cancer. We also would expect to see a leveling of the incidence of invasive vulvar cancer with age as is seen with invasive cervical cancer. Instead, there is a steady increase in incidence of invasive vulvar cancer with age. The differential age distributions between invasive vulvar and cervical cancers, particularly in combination with common patterns of in situ disease suggest that factors other than HPV are related to the development of invasive vulvar cancer for at least some cases.
A possible explanation for differences in age distribution between in situ and invasive vulvar carcinoma is that in situ vulvar disease is detected and treated before its progression to vulvar cancer. In cervical disease, Pap testing and early treatment of preinvasive disease have reduced the incidence of cervical cancer, yet these have not appreciably altered the age distribution, making this explanation unlikely for vulvar carcinoma.
This study relies on data from the SEER cancer registry. Although population based, it is limited because it does not include information about patients’ sexual history, tobacco use, menopausal history, or HPV and human immunodeficiency virus (HIV) status. However, the observed patterns are consistent with the interpretation that HPV infection, which is highly associated with vulvar carcinoma in situ, does not progress to vulvar cancer at the same rate as cervical carcinoma in situ progresses to cervical cancer. This finding may also be of relevance to anal intraepithelial neoplasia and invasive anal cancer, HPV-related cancers where the natural history and progression from in situ to invasive cancer is poorly understood, and should be studied further.25
We have demonstrated that the incidence of in situ vulvar carcinoma is increasing, similar to the increasing incidence of HPV in the population. In contrast, the incidence of invasive vulvar cancer has increased at a much lower rate, and the risk continues to increase with age. Although HPV may play a role in both vulvar cancer and cervical cancer, the development of these cancers are dissimilar. Additional factors should be evaluated.
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Footnotes |
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Presented at the 37th Annual Meeting of the Society of Gynecologic Oncologists, Palm Springs, California, March 22–26, 2006.
Corresponding author: Patricia L. Judson, MD, Division of Gynecologic Oncology, Department of Obstetrics, Gynecology, and Women’s Health, University of Minnesota, 420 Delaware Street SE, MMC 395, Minneapolis, MN 55455; e-mail: judso003{at}umn.edu.
doi:10.1097/01.AOG.0000210268.57527.a1
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REFERENCES |
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2. Sturgeon SR, Brinton LA, Devesa SS, Kurman RJ. In situ and invasive vulvar cancer incidence trends (1973 to 1987). Am J Obstet Gynecol 1992;166:1482–5.[Medline]
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20. Koutsky LA, Galloway DA, Holmes KK. Epidemiology of genital human papillomavirus infection. Epidemiol Rev 1988;10:122–63.
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| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
