Vulvar cancer: Epidemiology, diagnosis, histopathology, and treatment of rare histologies
- Jonathan S Berek, MD, MMS
Jonathan S Berek, MD, MMS
- Laurie Kraus Lacob Professor
- Stanford University School of Medicine
- Fellow, Stanford Distinguished Careers Institute
- Director, Stanford Women's Cancer Center
- Senior Scientific Advisor, Stanford Cancer Institute
- Amer Karam, MD
Amer Karam, MD
- Clinical Associate Professor
- Associate Director and Director of Outreach
- Division of Gynecologic Oncology
- Department of Obstetrics and Gynecology
- Stanford University School of Medicine
- Section Editors
- Barbara Goff, MD
Barbara Goff, MD
- Section Editor — Gynecologic Oncology
- Department Chair, Gynecologic Oncology
- University of Washington Medical Center
- Don S Dizon, MD, FACP
Don S Dizon, MD, FACP
- Section Editor – Gynecologic Oncology
- Head of Women's Cancers, Lifespan Cancer Institute
- Director of Medical Oncology, Rhode Island Hospital
- Associate Professor of Medicine, Warren Alpert Medical School of Brown University
Vulvar cancer is the fourth most common gynecologic malignancy in the United States (after uterine, ovarian, and cervical) . Squamous cell carcinoma is the most common histologic type of vulvar cancer, comprising at least 75 percent or more of cases [2,3]. Other histologies include melanoma, basal cell carcinoma, Bartholin gland adenocarcinoma, sarcoma, and Paget disease (table 1).
Human papillomavirus infection is associated with the majority of vulvar squamous cell carcinomas. In addition, vulvar lichen sclerosus is associated with an increased risk of vulvar cancers.
The epidemiology, clinical presentation, diagnosis, and histology of women with vulvar cancer will be reviewed here. Treatment of rare histologies is discussed here. Staging, treatment, and prognosis of squamous cell vulvar carcinoma are discussed separately. (See "Squamous cell carcinoma of the vulva: Staging and surgical treatment".)
In the United States (US), vulvar cancer is the fourth most common gynecologic malignancy (after uterine, ovarian, and cervical) . There are approximately 6000 cases and 1000 deaths from the disease each year.
Incidence rates by race or ethnicity in the US from 2010 to 2014 were: white (2.7 per 100,000 persons), black (1.8), Asian/Pacific Islander (0.9), Hispanic (1.8), and non-Hispanic (2.6) . In the United States, some data suggest that black women present with vulvar cancer at a younger age and have an increased probability of distant spread, which is a consistent finding across the different tumor models [5,6].To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2017. CA Cancer J Clin 2017; 67:7.
- Schuurman MS, van den Einden LC, Massuger LF, et al. Trends in incidence and survival of Dutch women with vulvar squamous cell carcinoma. Eur J Cancer 2013; 49:3872.
- Saraiya M, Watson M, Wu X, et al. Incidence of in situ and invasive vulvar cancer in the US, 1998-2003. Cancer 2008; 113:2865.
- https://seer.cancer.gov/statfacts/html/vulva.html (Accessed on April 28, 2017).
- Rauh-Hain JA, Clemmer JT, Bradford LS, et al. Racial disparities in cervical cancer survival over time. Cancer 2013; 119:3644.
- Jagsi R, Abrahamse P, Hawley ST, et al. Underascertainment of radiotherapy receipt in Surveillance, Epidemiology, and End Results registry data. Cancer 2012; 118:333.
- Madsen BS, Jensen HL, van den Brule AJ, et al. Risk factors for invasive squamous cell carcinoma of the vulva and vagina--population-based case-control study in Denmark. Int J Cancer 2008; 122:2827.
- Brinton LA, Thistle JE, Liao LM, Trabert B. Epidemiology of vulvar neoplasia in the NIH-AARP Study. Gynecol Oncol 2017; 145:298.
- de Koning MN, Quint WG, Pirog EC. Prevalence of mucosal and cutaneous human papillomaviruses in different histologic subtypes of vulvar carcinoma. Mod Pathol 2008; 21:334.
- Halec G, Alemany L, Quiros B, et al. Biological relevance of human papillomaviruses in vulvar cancer. Mod Pathol 2017; 30:549.
- Weberpals JI, Lo B, Duciaume MM, et al. Vulvar Squamous Cell Carcinoma (VSCC) as Two Diseases: HPV Status Identifies Distinct Mutational Profiles Including Oncogenic Fibroblast Growth Factor Receptor 3. Clin Cancer Res 2017; 23:4501.
- de Sanjosé S, Alemany L, Ordi J, et al. Worldwide human papillomavirus genotype attribution in over 2000 cases of intraepithelial and invasive lesions of the vulva. Eur J Cancer 2013; 49:3450.
- van de Nieuwenhof HP, Bulten J, Hollema H, et al. Differentiated vulvar intraepithelial neoplasia is often found in lesions, previously diagnosed as lichen sclerosus, which have progressed to vulvar squamous cell carcinoma. Mod Pathol 2011; 24:297.
- Bigby SM, Eva LJ, Fong KL, Jones RW. The Natural History of Vulvar Intraepithelial Neoplasia, Differentiated Type: Evidence for Progression and Diagnostic Challenges. Int J Gynecol Pathol 2016; 35:574.
- Zacur H, Genadry R, Woodruff JD. The patient-at-risk for development of vulvar cancer. Gynecol Oncol 1980; 9:199.
- Collins CG, Lee FY, Roman-Lopez JJ. Invasive carcinoma of the vulva with lymph node metastasis. Am J Obstet Gynecol 1971; 109:446.
- Hildesheim A, Han CL, Brinton LA, et al. Human papillomavirus type 16 and risk of preinvasive and invasive vulvar cancer: results from a seroepidemiological case-control study. Obstet Gynecol 1997; 90:748.
- Iwasawa A, Nieminen P, Lehtinen M, Paavonen J. Human papillomavirus in squamous cell carcinoma of the vulva by polymerase chain reaction. Obstet Gynecol 1997; 89:81.
- Al-Ghamdi A, Freedman D, Miller D, et al. Vulvar squamous cell carcinoma in young women: a clinicopathologic study of 21 cases. Gynecol Oncol 2002; 84:94.
- Elit L, Voruganti S, Simunovic M. Invasive vulvar cancer in a woman with human immunodeficiency virus: case report and review of the literature. Gynecol Oncol 2005; 98:151.
- Bosch FX, Manos MM, Muñoz N, et al. Prevalence of human papillomavirus in cervical cancer: a worldwide perspective. International biological study on cervical cancer (IBSCC) Study Group. J Natl Cancer Inst 1995; 87:796.
- Vinokurova S, Wentzensen N, Einenkel J, et al. Clonal history of papillomavirus-induced dysplasia in the female lower genital tract. J Natl Cancer Inst 2005; 97:1816.
- Castle PE, Schiffman M, Bratti MC, et al. A population-based study of vaginal human papillomavirus infection in hysterectomized women. J Infect Dis 2004; 190:458.
- de Giorgi V, Salvini C, Massi D, et al. Vulvar basal cell carcinoma: retrospective study and review of literature. Gynecol Oncol 2005; 97:192.
- Piura B, Rabinovich A, Dgani R. Basal cell carcinoma of the vulva. J Surg Oncol 1999; 70:172.
- Benedet JL, Miller DM, Ehlen TG, Bertrand MA. Basal cell carcinoma of the vulva: clinical features and treatment results in 28 patients. Obstet Gynecol 1997; 90:765.
- Piura B, Egan M, Lopes A, Monaghan JM. Malignant melanoma of the vulva: a clinicopathologic study of 18 cases. J Surg Oncol 1992; 50:234.
- Sugiyama VE, Chan JK, Shin JY, et al. Vulvar melanoma: a multivariable analysis of 644 patients. Obstet Gynecol 2007; 110:296.
- Stang A, Streller B, Eisinger B, Jöckel KH. Population-based incidence rates of malignant melanoma of the vulva in Germany. Gynecol Oncol 2005; 96:216.
- Chang AE, Karnell LH, Menck HR. The National Cancer Data Base report on cutaneous and noncutaneous melanoma: a summary of 84,836 cases from the past decade. The American College of Surgeons Commission on Cancer and the American Cancer Society. Cancer 1998; 83:1664.
- and Practice of Gynecologic Oncology, 2nd, Hoskins WJ, Perez CA, Young RC (Eds), Lippincott-Raven, 1997.
- Han CH, Li X, Khanna N. Epithelioid sarcoma of the vulva and its clinical implication: A case report and review of the literature. Gynecol Oncol Rep 2016; 15:31.
- Nasioudis D, Alevizakos M, Chapman-Davis E, et al. Rhabdomyosarcoma of the lower female genital tract: an analysis of 144 cases. Arch Gynecol Obstet 2017; 296:327.
- Parker LP, Parker JR, Bodurka-Bevers D, et al. Paget's disease of the vulva: pathology, pattern of involvement, and prognosis. Gynecol Oncol 2000; 77:183.
- Fanning J, Lambert HC, Hale TM, et al. Paget's disease of the vulva: prevalence of associated vulvar adenocarcinoma, invasive Paget's disease, and recurrence after surgical excision. Am J Obstet Gynecol 1999; 180:24.
- Feuer GA, Shevchuk M, Calanog A. Vulvar Paget's disease: the need to exclude an invasive lesion. Gynecol Oncol 1990; 38:81.
- DePasquale SE, McGuinness TB, Mangan CE, et al. Adenoid cystic carcinoma of Bartholin's gland: a review of the literature and report of a patient. Gynecol Oncol 1996; 61:122.
- Visco AG, Del Priore G. Postmenopausal bartholin gland enlargement: a hospital-based cancer risk assessment. Obstet Gynecol 1996; 87:286.
- Felix JC, Cote RJ, Kramer EE, et al. Carcinomas of Bartholin's gland. Histogenesis and the etiological role of human papillomavirus. Am J Pathol 1993; 142:925.
- Copeland LJ, Sneige N, Gershenson DM, et al. Bartholin gland carcinoma. Obstet Gynecol 1986; 67:794.
- Cardosi RJ, Speights A, Fiorica JV, et al. Bartholin's gland carcinoma: a 15-year experience. Gynecol Oncol 2001; 82:247.
- Fine BA, Munoz AK, Litz CE, Gershenson DM. Primary medical management of recurrent aggressive angiomyxoma of the vulva with a gonadotropin-releasing hormone agonist. Gynecol Oncol 2001; 81:120.
- Martelli H, Oberlin O, Rey A, et al. Conservative treatment for girls with nonmetastatic rhabdomyosarcoma of the genital tract: A report from the Study Committee of the International Society of Pediatric Oncology. J Clin Oncol 1999; 17:2117.
- Shepherd V, Davidson EJ, Davies-Humphreys J. Extramammary Paget's disease. BJOG 2005; 112:273.
- Niikura H, Yoshida H, Ito K, et al. Paget's disease of the vulva: clinicopathologic study of type 1 cases treated at a single institution. Int J Gynecol Cancer 2006; 16:1212.
- Tebes S, Cardosi R, Hoffman M. Paget's disease of the vulva. Am J Obstet Gynecol 2002; 187:281.
- Hendi A, Brodland DG, Zitelli JA. Extramammary Paget's disease: surgical treatment with Mohs micrographic surgery. J Am Acad Dermatol 2004; 51:767.
- Zollo JD, Zeitouni NC. The Roswell Park Cancer Institute experience with extramammary Paget's disease. Br J Dermatol 2000; 142:59.
- O'Connor WJ, Lim KK, Zalla MJ, et al. Comparison of mohs micrographic surgery and wide excision for extramammary Paget's disease. Dermatol Surg 2003; 29:723.
- Yokoyama Y, Mabuchi M, Kawabata I, et al. Metastatic vulvar Paget's disease responding to combination chemotherapy: case report. Jpn J Clin Oncol 1990; 20:426.
- Yamamoto R, Sakuragi N, Shirato H, et al. Radiotherapy with concurrent chemotherapy for vulvar adenocarcinoma associated with extramammary Paget's disease. Gynecol Oncol 2001; 80:267.
- Huang GS, Juretzka M, Ciaravino G, et al. Liposomal doxorubicin for treatment of metastatic chemorefractory vulvar adenocarcinoma. Gynecol Oncol 2002; 87:313.
- Hatch KD, Davis JR. Complete resolution of Paget disease of the vulva with imiquimod cream. J Low Genit Tract Dis 2008; 12:90.
- Son SH, Lee JS, Kim YS, et al. The role of radiation therapy for the extramammary paget's disease of the vulva ; experience of 3 cases. Cancer Res Treat 2005; 37:365.
- Sendagorta E, Herranz P, Feito M, et al. Successful treatment of three cases of primary extramammary Paget's disease of the vulva with Imiquimod--proposal of a therapeutic schedule. J Eur Acad Dermatol Venereol 2010; 24:490.
- Hata M, Omura M, Koike I, et al. Role of radiotherapy as curative treatment of extramammary Paget's disease. Int J Radiat Oncol Biol Phys 2011; 80:47.
- Brummer O, Stegner HE, Böhmer G, et al. HER-2/neu expression in Paget disease of the vulva and the female breast. Gynecol Oncol 2004; 95:336.
- Richter CE, Hui P, Buza N, et al. HER-2/NEU overexpression in vulvar Paget disease: the Yale experience. J Clin Pathol 2010; 63:544.
- Balat O, Edwards CL, Delclos L. Advanced primary carcinoma of the Bartholin gland: report of 18 patients. Eur J Gynaecol Oncol 2001; 22:46.
- Massad LS, De Geest K. Multimodality therapy for carcinoma of the Bartholin gland. Gynecol Oncol 1999; 75:305.
- Yamada T, Yanagawa S, Iwai H, et al. High-dose-rate interstitial brachytherapy of Bartholin's gland: A case report. Gynecol Oncol 2000; 77:193.
- López-Varela E, Oliva E, McIntyre JF, Fuller AF Jr. Primary treatment of Bartholin's gland carcinoma with radiation and chemoradiation: a report on ten consecutive cases. Int J Gynecol Cancer 2007; 17:661.
- Downs LS, Ghosh K, Dusenbery KE, Cosin JA. Stage IV carcinoma of the Bartholin gland managed with primary chemoradiation. Gynecol Oncol 2002; 87:210.
- Tanaka H, Umekawa T, Nagao K, et al. Adenocarcinoma of mammary-like glands in the vulva successfully treated by weekly paclitaxel. Int J Gynecol Cancer 2005; 15:568.
- RISK FACTORS AND ETIOLOGY
- CLINICAL PRESENTATION
- Vulvar lesion
- Vulvar pruritus
- Other presentations
- DIAGNOSTIC EVALUATION
- DIFFERENTIAL DIAGNOSIS
- HISTOLOGIC TYPES
- Squamous cell carcinoma
- - Verrucous carcinoma
- Basal cell carcinoma
- Paget disease of the vulva
- Bartholin gland carcinoma
- TREATMENT OF RARE HISTOLOGIES
- Verrucous carcinoma
- Basal cell carcinoma
- Paget disease of the vulva
- Bartholin gland carcinoma
- SUMMARY AND RECOMMENDATIONS