Incidences and risk factors of metachronous vulvar, vaginal, and anal cancers after cervical cancer diagnosis.

OBJECTIVE: To examine incidences and risk factors for metachronous vulvar, vaginal, and anal malignancies after a cervical cancer diagnosis. METHODS: This is a retrospective study examining data from the Surveillance, Epidemiology, and End Result Program between 1973 and 2013. Cumulative incidences of vulvar, vaginal, and anal cancers after the diagnosis of cervical cancer were assessed (n = 79,050). Multivariable analysis was performed to determine independent risk factors for these metachronous cancers. RESULTS: Vaginal cancer (20-year cumulative incidence, 0.57%) was the most common type of metachronous malignancy, followed by vulvar cancer (0.33%), and anal cancer (0.16%, P < 0.001). Median time to diagnosis was 5.4 years for vaginal cancer, 6.5 years for vulvar cancer, and 13.5 years for anal cancer. On multivariable analysis, metachronous vulvar cancer was associated with older age (hazard ratio [HR] per year 1.04, 95% confidence interval [CI] 1.02-1.05, P < 0.001), squamous histology (HR 2.64, 95%CI 1.38-5.05, P = 0.003), and radiotherapy use (HR 2.52, 95%CI 1.66-3.84, P < 0.001); metachronous vaginal cancer was associated with older age (HR per year 1.03, 95%CI 1.02-1.04, P < 0.001) and Black race (HR 1.73, 95%CI 1.20-2.48, P = 0.003); and metachronous anal cancer was associated with older age (HR 1.03, 95%CI 1.01-1.05, P = 0.017). Overall survival of metachronous cancer was poor (5-year rates: 46.3% for vulvar, 43.0% for vaginal, and 47.5% for anal cancer, respectively). CONCLUSION: Although rare, the rate of ano-genital cancers continues to increase over time after a cervical cancer diagnosis. Long-term follow-up and surveillance after cervical cancer treatment is therefore reasonable to detect these metachronous malignancies, particularly in those with risk factors.

Vulvar and Vaginal Cancer, Vulvar Intraepithelial Neoplasia 3 and Vaginal Intraepithelial Neoplasia 3: Experience of a Referral Institute.

BACKGROUND: Vulvar and vaginal malignant and premalignant lesions are uncommon and are clinically heterogeneous diseases with two pathways of carcinogenesis: human papillomavirus (HPV) induced or non-HPV induced. OBJECTIVES: To evaluate the demographic and clinical characteristics associated with vulvar or vaginal cancer and vulvar and vaginal intraepithelial neoplasia 3 (VIN3, VAIN3). METHODS: We conducted a retrospective chart review of 148 women with vulvar and vaginal malignancy and pre-malignancy for the period October 2004 to October 2012, and identified 59 and 19 patients with vulvar and vaginal cancer respectively, and 57 and 13 patients with VIN3 and VAIN3 respectively RESULTS: The median age of vulvar cancer patients was 30 years older than that of VIN3 patients. HPV was found in 60% and 66.6% of vulvar and vaginal cancer patients respectively, and in 82.3% and 84.6% of patients with VIN3 and VAIN3 respectively. A history of cervical intraepithelial neoplasia (CIN) or warts was observed in 10% and 10.5% of vulvar and vaginal cancer patients respectively, and in 57.9% and 46% of patients with VIN3 and VAIN3 respectively. In 52.6% of patients the vaginal cancer was metastases from other organs. CONCLUSIONS: Most women with vulvar carcinoma are older than 70 years. VIN3 and VAIN3 are associated with HPV infection and the most prevalent type is HPV16. Almost half the vaginal cancers are associated with metastases from other organs and almost half of VAIN3 is associated with past cervical dysplasia or carcinoma.

Vulvar/vaginal melanoma: an updated surveillance epidemiology and end results database review, comparison with cutaneous melanoma and significance of racial disparities.

OBJECTIVE: We aimed to compare the differences in demographic features, clinicopathologic features, and survival in patients with vulvar/vaginal melanoma versus cutaneous melanoma with a special emphasis on race. MATERIALS AND METHODS: Data were obtained from the Surveillance Epidemiology and End Results database from 1973 to 2008. Kaplan-Meier curves and Cox multivariate model were used for statistical analysis. RESULTS: Seven hundred sixty-two patients with vulvar/vaginal melanoma and 55,485 patients with cutaneous melanoma patients were included in the study. Twenty-eight patients of the vulvar/vaginal group and 334 patients of the cutaneous group were black (3.6% vs 0.6%, respectively). The median age at the time of diagnosis was 68 years in the vulvar/vaginal group and 52 years in the cutaneous group (P < 0.0001). Three hundred fifty patients (45.9%) in the vulvar/vaginal and 46,499 patients (83.8%) in the cutaneous group presented with localized disease (P < 0.0001), whereas 64 patients (8.4%) in the vulvar/vaginal group and 1520 patients (2.7%) in cutaneous group presented with advanced disease (P = 0.0081). The median survival of the black patients was 16 months in the vulvar/vaginal group and 124 months in the cutaneous melanoma group (P < 0.0001). The median survival in the nonblack population was 39 months in the vulvar/vaginal group compared to 319 months in the cutaneous melanoma group (P <0.0001). In multivariate analysis performed for patients between 1988 and 2008, age, stage, and positive lymph nodes were negative independent prognostic factors for survival in vulvar/vaginal melanoma; whereas age, race, stage, radiation therapy, and lymph node positivity were negative prognostic factors in cutaneous melanoma. CONCLUSION: These findings emphasize that cutaneous and vulvar/vaginal melanomas have different clinicopathologic features and survival patterns.

Effect of human immunodeficiency virus infection on the prevalence and incidence of vaginal intraepithelial neoplasia.

OBJECTIVE: To estimate the prevalence, incidence, and clearance of abnormal vaginal cytology and vaginal intraepithelial neoplasia (VAIN) in human immunodeficiency virus (HIV)-seropositive women. METHODS: Pap tests were done semiannually for 335 HIV-seropositive and 75 HIV-seronegative women with prior hysterectomy in the prospective Women's Interagency HIV Study cohort. End points included abnormal Pap test results after hysterectomy and VAIN regardless of hysterectomy. RESULTS: Over a median of 5.6 years of follow-up, vaginal Pap test results were abnormal at 1,076 (29%; 95% confidence interval [CI] 25-33%) of 3,700 visits among HIV-seropositive compared with 31 (4%; 95% CI 2-8%) of 763 visits among HIV-seronegative women (P<.001). Abnormal Pap test results included 641 atypical squamous cells of undetermined significance, 425 low-grade squamous intraepithelial lesions, and 10 high-grade squamous intraepithelial lesions in HIV-seropositive women and 28 atypical squamous cells of undetermined significance and three low-grade squamous intraepithelial lesions in HIV-seronegative women. The incidence of abnormal Pap test results after hysterectomy was 14 per 100 person-years among HIV-seropositive and two per 100 person-years among HIV-seronegative women (P<.001) and remained stable across time. The 5-year clearance rate of abnormal Pap test results was 34 per 100 person-years for HIV-seropositive and 116 per 100 person-years for HIV-seronegative women (P<.001). In multivariate regression models, women with lower CD4 counts were more likely to have and less likely to clear abnormal cytology when it occurred. The incidence of VAIN 2 or worse was 0.2 and 0.01 per 100 person-years for HIV-seropositive and HIV-seronegative women (P=.001). Two HIV-seropositive women developed stage II cancers with remission after radiotherapy. CONCLUSION: Vaginal Pap test results are often abnormal in HIV-seropositive women. Although more common than in HIV-seronegative women, VAIN 2 or worse and especially vaginal cancers are infrequent.

Disparities in treatment and survival between African American and White women with vaginal cancer.

OBJECTIVE: The study aims to compare the difference in treatment and survival between White (W) and African American (AA) patients with vaginal cancer (VC). METHODS: Patients with a diagnosis of invasive vaginal cancer were identified from Surveillance, Epidemiology, and End Results (SEER) program from 1988 to 2007 and were divided into White (W) and African American (AA) subgroups. Student's t test, Kaplan-Meier survival methods, and Cox regression proportional hazards were performed. RESULTS: A total of 2675 patients met the inclusion criteria, with histologic distribution of squamous cell carcinoma (SCC; 2190, 82%) and adenocarcinoma (AC; 485, 18%); 2294 (85.8%) were W, and 381 (14.2%) were AA. Median age was 69 for W and 65 for AA (p<0.001). SCC and AC were equally distributed between W and AA. Advanced stage disease (FIGO III and IV) was more prominent in AA compared with W (30.4% vs. 23.1%, p=0.019). Radiation therapy was utilized equally in both racial groups; however, surgical treatment alone or combined with radiation therapy was more frequent in W compared with AA (27.7% vs. 17.5%, p<0.001). The 5-year survival was 45% in W and 38.6% in AA (p=0.008). In multivariate analysis, AA had significantly poorer survival compared with Whites when controlling for age, histology, stage, grade and treatment modality (HR 1.2, 95% CI 1.1-1.4, p=0.007). CONCLUSIONS: African American women with vaginal cancer were more likely to present, at a younger age, advanced stage and less likely to receive surgical treatment. Our data suggests that AA race is an independent predictor of poor survival in vaginal cancer.

Population-based incidence of vulvar and vaginal melanoma in various races and ethnic groups with comparisons to other site-specific melanomas.

Little is known on the difference in the incidence of vulvar and vaginal melanomas in various racial/ethnic groups. Population-based incidence of these melanomas in Asian and Hispanic individuals is almost unknown. Using 1992-2005 data provided by the National Cancer Institute's Surveillance, Epidemiology, and End Results Program, we calculated age-adjusted incidence rates of vulvar and vaginal melanomas in various racial/ethnic groups. From 1992 to 2005, there were 324 vulvar melanomas and 125 vaginal melanomas diagnosed in this group. The annual age-adjusted incidence rates (per million female population) of vulvar and vaginal melanomas in the different racial/ethnic groups was 0.87 (Blacks), 0.75 (American-Indian), 1.03 (Asians and Pacific Islanders), 1.22 (Hispanics), and 1.90 (non-Hispanic Whites). The overall white/black incidence ratio in vulvar and vaginal melanomas was 3.14 : 1 and 1.02 : 1, respectively; which is much less than that of cutaneous melanoma (13 : 1-17 : 1) and uveal melanoma (18 : 1) and is similar to that of conjunctival melanoma (2.6 : 1) and other mucosal melanomas (2.1 : 1-2.3 : 1). The low racial difference in vulvar and vaginal melanomas (as well as conjunctival and other mucosal melanomas) may be determined by their microenvironment factors (all originate from mucosa or semi-mucosa tissues). The incidence of vulvar and vaginal melanomas has does not increased in recent decades or toward the south (more sun exposure), indicating that ultraviolet radiation is not a causative factor in these melanomas. The slight decrease of incidence of vulvar melanoma in dark pigmented individuals may be related to the biochemical protective effects of melanin (as an antioxidant) rather than their photo-screen effects.

Descriptive epidemiology of vaginal cancer incidence and survival by race, ethnicity, and age in the United States.

BACKGROUND: Vaginal cancer is a rare malignancy. It has many of the same risk factors as cervical cancer, including a strong association with persistent human papillomavirus infection. Descriptive studies of the epidemiology of vaginal cancer are scarce in the literature. METHODS: The 1998 through 2003 incidence data from 39 population-based cancer registries were used, covering up to 83% of the US population. The 1996 through 2003 data from 17 cancer registries were used for survival analysis. Incidence rates, disease stage, and 5-year relative survival rates were calculated by race, ethnicity, and age group. Data analysis focused mainly on squamous cell carcinoma (SCC). RESULTS: Incidence rates for all vaginal cancers combined were 0.18 per 100,000 female population for in situ cases and 0.69 for invasive cases. The median age of invasive cases was older than that of in situ cases (aged 68 years vs 58 years). SCC was the most common histologic type (71% of in situ cases and 66% of invasive cases). Compared with the rate for white women, the age-adjusted incidence rate of invasive SCC was 72% higher (P < .05) among black women, whereas the rate among Asian/Pacific Islander (API) women was 34% lower (P < .05). Hispanic women had a 38% higher rate than non-Hispanic women (P < .05) of invasive SCC. The rates for in situ SCC peaked at age 70 years and then declined, whereas the rates of invasive SCC increased continuously with advancing age. Black, API, and Hispanic women as well as 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. CONCLUSIONS: Incidence rates of vaginal SCC varied significantly by race, ethnicity, and age group. Black, API, and Hispanic women as well as older women had a high proportion of late-stage disease and a low 5-year survival rate.

Human papillomavirus-associated carcinomas in Hawaii and the mainland U.S.

BACKGROUND: To the authors' knowledge, human papillomavirus (HPV)-associated carcinomas in Hawaii have not been studied in detail. METHODS: Surveillance, Epidemiology, and End Results data (from 1973-1996) were used to study rate of incidence patterns of squamous cell carcinomas (SCCs) of the uterine cervix, vulva/vagina, anus, penis, and palatine tonsils among Asian/Pacific Islanders and whites in Hawaii and among whites in the U.S. in general. RESULTS: With the exception of invasive cervical SCC, male and female Asian/Pacific Islanders in Hawaii had considerably lower incidence rates of HPV-associated SCCs than Hawaii whites and U.S. whites. Among women, Hawaii whites and U.S. whites had rather similar rates of invasive anogenital and tonsillar SCCs, but in situ SCC of the cervix or vulva/vagina was diagnosed less often among Asian/Pacific Islanders and whites in Hawaii than among whites in the general U.S. Among men, Hawaii whites had higher rates than U.S. whites of both anal and tonsillar, but not penile, SCCs. Among Hawaiian men with anal carcinoma, 43% (15 of 35) had remained unmarried versus 3% (2 of 65) of Hawaiian women with anal carcinoma. CONCLUSIONS: Asian/Pacific Islanders in Hawaii generally have lower incidence rates of HPV-associated SCCs than whites. However, low ratios of in situ to invasive cervical SCCs suggest that many Hawaii women, notably Asian/Pacific Islanders, are not diagnosed and treated for cervical neoplasias at a preinvasive stage. The high rate of incidence of anal SCC in male Hawaiian whites and the high proportions of unmarried men among patients with this disease suggest the transmission of HPV through homosexual contact. These men may be targeted in future screening programs for anal carcinoma.

Malignant melanoma of the vulva and vagina in the United States: patterns of incidence and population-based estimates of survival.

OBJECTIVES: Our purpose was to describe the incidence of vulvar and vaginal melanoma and to evaluate risk factors. We also aimed to provide population-based estimates of survival and to evaluate prognostic factors. STUDY DESIGN: We calculated incidence rates and survival curves based on 15 years' experience of population-based registries that together cover approximately 10% of the United States population. RESULTS: The incidences of vulvar and vaginal melanoma were 0.108 and 0.026/10(5) per year. White women experienced an increased incidence of vulvar melanoma but not vaginal melanoma (relative risks 2.6 and 1.0 for white women, compared with black women). For vulvar melanoma the 5-year survival was 50%; regional or distant spread, older age, and black race were adverse prognostic factors. For vaginal melanoma the 5-year survival was 19%; black race was an adverse prognostic factor. CONCLUSIONS: Vulvar melanoma and vaginal melanoma differ from nongenital cutaneous melanoma in epidemiologic features, which is consistent with the hypothesized systemic sun-induced melanoma-inhibitory factor and with melanin interference with nonultraviolet carcionogenesis. These population-based data identified prognostic factors and confirmed the poor prognosis of these tumors.

FIGO stage, histology, histologic grade, age and race as prognostic factors in determining survival for cancers of the female gynecological system: an analysis of 1973-87 SEER cases of cancers of the endometrium, cervix, ovary, vulva, and vagina.

The prognostic impact of FIGO stage, histology, histologic grade, age and race in survival for cancers of the female gynecological (cervix, endometrium, ovary, vulva, vagina) were examined using cases obtained from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program that were diagnosed between 1973 and 1987. Utilizing Cox proportional hazards modeling and relative survival rates analysis of 17,119 cases of cervical cancer indicated that the International Federation of Gynecology and Obstetrics (FIGO) stage, histology, histological grade, lymph node status, and age at diagnosis were all independently prognostic. No evidence was found of survival differences between squamous cell carcinoma and adenocarcinoma. Younger women were not found to have a poorer prognosis, survival declined with increased age. Analysis of 41,120 cases of endometrial cancer indicated that FIGO stage, histology, histologic grade, lymph node status, age at diagnostic, and race were all prognostic factors. Clear cell adenocarcinoma, leiomyosarcoma, and mixed mullerian tumors were all found to have poorer prognosis. Analysis of 21,240 cases of ovarian cancer indicated that FIGO stage, histology, histologic grade, lymph node status, age at diagnosis, presence of ascites, and race were all prognostically significant. Analysis of 2,575 cases of vulvar cancer indicated that FIGO stage, histology, histologic grade, age, and race were all prognostically significant. Analysis of 916 cases of vaginal cancer indicated that FIGO stage, histologic grade, lymph node status, and age are all prognostically significant. Additional analysis of the data by combinations of independent prognostic factors indicates that the interaction of factors may be more predictive of outcome than any one factor separately.

The need for Pap tests after hysterectomy for benign disease. Results of a study of black patients.

The questions of whether a Pap test should be done in patients who have undergone hysterectomy for benign uterine disease and, if so, how often were addressed by reviewing the records of 3,008 black women seen in a cancer screening clinic. No vaginal carcinoma was found in the posthysterectomy patients or in the control group with the uterus in place. The absence of carcinoma in the posthysterectomy group suggests that although an annual physical examination is indicated, the time interval between performance of the Pap test may be lengthened.