Volume 200, Issue 5 , Pages e52-e55, May 2009
A comparison of younger vs older women with vulvar cancer in the United States
Article Outline
Objective
The purpose of this study was to compare the prognostic variables and survival of younger (< 50 years) to that of older (≥ 50 years) women with vulvar cancer.
Study Design
Subjects with invasive squamous cell carcinoma of the vulva were identified from the limited use Surveillance, Epidemiology, and End Results (SEER) Program 1988-2005. Comparisons between younger and older women were accomplished with χ2 and t-tests. Survival analysis was accomplished with Kaplan-Meier for univariate analysis and Cox proportional hazards model for multivariate analysis.
Results
A total of 6965 patients met inclusion criteria, of whom 1345 patients (19.3%) were younger and 5620 patients (80.7%) were older. The 5-year survival was 87.5% for younger women and 52.5% for older women (P < .001). After data were controlled for race, stage, grade, and surgical treatment, older patients had a hazard ratio of 3.9 (95% CI, 3.2-4.7) for death.
Conclusion
A striking survival difference exists between younger and older women with squamous cell vulvar cancer, which supports the view that etiopathogenesis of this disease may vary between age groups.
Key words: age of diagnosis, survival, vulvar cancer
Vulvar cancer is the fourth most common gynecologic cancer in the United States, with an estimated 3460 new cases and 870 deaths in 2008.1 It has been proposed that squamous cell carcinoma of the vulva (SCCV) may be divided into 2 main variants. One variant is human papillomavirus (HPV) related, which occur in younger women in the form of warty or basaloid morphology. The other variant is the more common HPV-unrelated lesion, which occurs in older women in association with lichen sclerosis or squamous hyperplasia.2, 3
Evidence suggests that the incidence of vulvar intraepithelial neoplasia (a probable precursor) and that of invasive vulvar cancer is rising.4 This increasing incidence has shown predilection towards younger women, with recent reports of a striking increase in the fraction of vulvar cancer that has occurred in < 50-year age group from 11-41%.5
Despite the fact that the etiopathogenesis of vulvar cancer is proposed to be different in younger vs older women and that the rising incidence of vulvar cancer has affected the younger women disproportionately,5 systematic large scale investigations that focus on prognostic variables in younger vs older women remain absent in the literature. Smaller studies provide conflicting information regarding the prognostic significance of age of diagnosis in this disease, with some investigators suggesting that age is of prognostic value,6 whereas other investigators report the contrary.7
The objective of this study was to compare the prognostic variables and survival of younger (< 50 years old) with that of older (≥ 50 years old) women with SCCV.
Materials and Methods
Subjects were identified from the limited use Surveillance, Epidemiology, and End Results (SEER) Program, 1988-2005.8 Inclusion criteria were a diagnosis of invasive SCCV, active follow-up evaluation, and known age of diagnosis. Subjects with non-squamous cell histologic condition and a diagnosis by autopsy or death certificate were excluded. Two cohorts were created on the basis of age of diagnosis: younger (< 50 years) and older (≥ 50 years). Stage was defined as local (FIGO I&II), regional (FIGO III), and distant (FIGO IV). Survival analysis used deaths that were attributable to SCCV.
The χ2 test and parametric t-tests were used for comparisons between younger and older women. The log-rank test with Kaplan-Meier model was used for survival comparisons. Multivariate analysis with Cox proportional hazards model in a forward stepwise method (conditional logistic regression [LR]) was performed. All probability values that are reported are 2-tailed, and a probability value of ≤ .05 was considered to be statistically significant. This study received exempt status from the institutional review board of Wayne State University.
Results
A total of 6965 patients met inclusion criteria: 1345 women (19.3%) were younger, and 5620 women (80.7%) were older. The mean age was 42 years (range, 12-49 years) in the former cohort and 73 years (range, 50-102 years) in the latter cohort (P < .001). The grade distribution was similar in the 2 groups. Table 1 presents multiple prognostic variables by cohort. White women formed 81% of the younger cohort and 90% of the older cohort. African American women were at least twice as likely (15% vs 7%; P < .001) to be in the younger cohort. Other racial groups were distributed equally in the 2 cohorts. Younger women were more likely to have localized disease (74% vs 61%; P < .001), whereas the older group were more likely to have regional (35% vs 24%) or distant (4.6% vs 2%) disease (P < .001). Consequently, the surgical treatment was more prevalent in the younger group (92% vs 84%; P < .001), whereas radiation therapy was more frequent in the older age group (27% vs 16%; P < .001).
TABLE 1. Prognostic variables in younger vs older women with invasive squamous cell cancer of vulva, 1988-2005
| Variable | Group | P value | |||
|---|---|---|---|---|---|
| Younger (< 50 y)a | Older (≥ 50 y)b | ||||
| n | Percentage | n | Percentage | ||
| Race | |||||
| White | 1084 | 80.6 | 5040 | 89.7 | .001 |
| African American | 213 | 15.8 | 401 | 7.1 | |
| Other | 48 | 3.6 | 179 | 3.2 | < .05 |
| Grade | |||||
| Well-differentiated | 664 | 81.6 | 3454 | 78.1 | <.05 |
| Poorly differentiated | 150 | 18.4 | 967 | 21.9 | |
| Stage | |||||
| Local | 965 | 74.3 | 3239 | 60.6 | .001 |
| Regional | 307 | 23.7 | 1862 | 34.8 | |
| Distant | 26 | 2.0 | 248 | 4.6 | |
| Surgery | |||||
| Yes | 1235 | 92.2 | 4707 | 84.1 | .001 |
| No | 105 | 7.8 | 893 | 15.9 | |
| Radiation | |||||
| Yes | 214 | 16.2 | 1498 | 26.9 | .001 |
| No | 1110 | 83.8 | 4070 | 73.1 | |
| Status | |||||
| Alive | 1148 | 85.4 | 2836 | 50.5 | |
| Dead | 197 | 14.6 | 2784 | 49.5 | |
| Total sample | 1345 | 100 | 5620 | 100 | |
aMedian age, 43 years; mean age, 42 years; P = .001. |
bMedian age, 74 years; mean age, 73 years. |
The 5-year survival rate was 87.5% for the younger women, compared with 52.5% for the older women (Figure 1; P < .001). Median survival was not reached for the younger cohort but was 68 months for the older cohort (P < .001). The comparative 5-year survival rate at each stage was worse for older women: localized, 93% vs 66% (P = .001); regional, 79% vs 38% (P = .001); distant, 26% vs 11% (P = .1). In the surgically treated patients, the 5-year survival rate was 90% for the younger group compared with 58% in the older group (Figure 2; P < .001).
FIGURE 1.
Comparison of survival of younger patients (< 50 years; blue line) with that of older patients (≥ 50 years; green line) with squamous cell cancer of the vulva, 1988-2005. Log rank: P = .001.
Kumar. A comparison of younger vs older women with vulvar cancer in the United States. Am J Obstet Gynecol 2009.
FIGURE 2.
Comparison of survival of younger patients (< 50 years; blue line) with that of older patients (≥ 50 years; green line) with surgically treated squamous cell cancer of the vulva, 1988-2005. Log rank: P = .001.
Kumar. A comparison of younger vs older women with vulvar cancer in the United States. Am J Obstet Gynecol 2009.
In a multivariate analysis, age group, race, stage, grade, and surgical treatment were independent predictors of survival (Table 2). In this model, radiotherapy did not have a significant independent impact on prognosis (P > .05). As shown in Table 2, older patients had a hazard ratio of 3.9 (95% CI, 3.2-4.7) for death after data were controlled for race, stage, grade, and surgical treatment.
TABLE 2. Multivariate analysis displays independent predictors of survival in SCCV, 1988-2005
| Variable | Hazard ratio | 95% CI | P value |
|---|---|---|---|
| Age group | |||
| Older (≥ 50 y) | 3.928 | 3.267-4.724 | .001 |
| Younger (< 50 y) | 1 | — | |
| Stage | |||
| Distant | 4.601 | 3.906-5.419 | .001 |
| Regional | 1.960 | 1.790-2.146 | .001 |
| Localized | 1 | — | |
| Surgery | |||
| No | 2.272 | 2.027-2.547 | .001 |
| Yes | 1 | — | |
| Grade | |||
| Poorly differentiated | 1.249 | 1.135-1.375 | .001 |
| Well-differentiated | 1 | — | |
| Race | |||
| Other | 0.803 | 0.617-1.045 | .103 |
| African American | 0.750 | 0.632-0.891 | .001 |
| White | 1 | — |
Comment
This is the largest retrospective study to present a comparison of prognostic variables of SCCV in younger vs older women. These data emphasize that, in younger women, SCCV is diagnosed at a comparatively early stage and more likely to have surgical treatment, whereas the older women are more likely to have advanced disease with a higher prevalence of radiotherapy. Our results display a striking difference in survival between the 2 age groups, with the younger women surviving considerably longer than the older women. The better survival in younger women may contribute to, but not be entirely explained by, the higher prevalence of early stage disease or surgical treatment. This is supported by our results of univariate analysis that show that the survival in younger women is better than older women at each stage; even when data from only surgically treated patients were analyzed, the same conclusion persisted. Further, multivariate analysis suggested that the risk of death on moving from younger to older age is roughly as pronounced as of moving from localized disease to distant disease (compare the hazard ratio; Table 2).
One might assume that older women may have worse survival rates than the younger women, by virtue of the age itself. However, that assumption may not be true in every clinical scenario. For example, several studies have shown that younger women with breast cancer have poorer prognosis than the older women.9 Moreover, age may influence disease outcomes by affecting genetic, pathologic, therapeutic, environmental, or societal variables of the disease, which in turn may affect the survival. Our study attempts to shed light on the probable influence of age on the distribution of various prognostic variables in SCCV.
Limitations of our study include its retrospective nature, lack of information on patient comorbidities, chemotherapy, and disease recurrence. However, this is a large study that overcomes several limitations of single institutional studies (such as selection and referral bias), and the results of this study may have better external applicability because the SEER registries cover 26% of the US population (http://www.seer.cancer.gov/).
Several studies report that the vulvar cancer in younger women is almost always associated with HPV infection, whereas it may have different risk factors at older age.2, 3 Our data provide indirect epidemiologic evidence that the HPV-related vulvar cancer may carry a better prognosis indeed. Complementary findings were reported by Monk et al,10 which show that HPV DNA was an independent predictor of better survival in vulvar cancer. Our study supports the idea of a dichotomy in etiopathogenesis of vulvar cancer in younger vs older women and provides clinically useful information for patient counseling. The better prognosis in younger women in the face of a rising incidence of vulvar cancer is reassuring. Suggestions to improve the survival of the older women include increasing awareness to seek early medical advice for any vulvar symptoms and earlier diagnosis and consideration for more aggressive therapies once the diagnosis is established.
References
- Cancer statistics, 2008. CA Cancer J Clin. 2008;58:71–96
- . Heterogeneous etiology of squamous carcinoma of the vulva. Obstet Gynecol. 1996;87:59–64
- Vulvar squamous cell carcinoma in young women: a clinicopathologic study of 21 cases. Gynecol Oncol. 2002;84:94–101
- Annual report to the nation on the status of cancer (1973 through 1998), featuring cancers with recent increasing trends. J Natl Cancer Inst. 2001;93:824–842
- . New aspects of vulvar cancer: changes in localization and age of onset. Gynecol Oncol. 2008;109:340–345
- . Intraepithelial and invasive squamous cell neoplasia of the vulva: trends in incidence, recurrence, and survival rate in Norway. Obstet Gynecol. 1998;91:969–972
- . Carcinoma of the vulva in young women. Obstet Gynecol. 1995;86:51–54
- . Surveillance, Epidemiology, and End Results (SEER) program SEER*stat database: incidence - SEER 17 regs limited-use + hurricane Katrina impacted Louisiana cases, Nov 2007 sub (1973-2005 varying) - linked to county attributes - total US, 1969-2005 counties, National Cancer Institute, DCCPS, Surveillance Research Program, Cancer Statistics Branch, released April 2008, based on the November 2007 submission, 2008. www.seer.cancer.govAccessed May 5, 2008
- . Do young breast cancer patients have worse outcomes?. J Surg Res. 2003;113:109–113
- . Prognostic significance of human papillomavirus DNA in vulvar carcinoma. Obstet Gynecol. 1995;85:709–715
Authorship and contribution to the manuscript is limited to the 6 authors indicated. There was no outside funding or technical assistance with the production of this article.
PII: S0002-9378(08)01094-6
doi:10.1016/j.ajog.2008.09.869
© 2009 Mosby, Inc. All rights reserved.
Volume 200, Issue 5 , Pages e52-e55, May 2009
