- 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
- Jonathan S Berek, MD, MMS
Jonathan S Berek, MD, MMS
- Laurie Kraus Lacob Professor
- Director, Stanford Women's Cancer Center
- Stanford Comprehensive Cancer Institute
- Chair, Department of Obstetrics & Gynecology
- Stanford University School of Medicine
- Elizabeth A Kidd, MD
Elizabeth A Kidd, MD
- Assistant Professor
- Department of Radiation Oncology
- Stanford University
- Section Editors
- Barbara Goff, MD
Barbara Goff, MD
- Section Editor — Gynecologic Oncology
- Professor of Gynecologic Oncology
- University of Washington
- Arno J Mundt, MD
Arno J Mundt, MD
- Section Editor — Radiation Therapy
- Chairman of Radiation Oncology
- University of California, San Diego
- Don S Dizon, MD, FACP
Don S Dizon, MD, FACP
- Section Editor – Gynecologic Oncology
- Clinical Co-Director, Gynecologic Oncology
- Founder and Director, The Oncology Sexual Health Clinic
- Massachusetts General Hospital Cancer Center
- Associate Professor of Medicine
- Harvard Medical School
- Deputy Editors
- Sadhna R Vora, MD
Sadhna R Vora, MD
- Deputy Editor — Oncology
- Instructor in Medicine
- Harvard Medical School
- Sandy J Falk, MD, FACOG
Sandy J Falk, MD, FACOG
- Director, Editorial Relations — UpToDate
- Deputy Editor — Obstetrics, Gynecology and Women's Health
- Instructor of Obstetrics, Gynecology and Reproductive Biology, Part-time
- Harvard Medical School
Primary cancer of the vagina comprises approximately three percent of all malignant neoplasms of the female genital tract. In the United States for example, vaginal cancer accounts for approximately 4000 cases and over 900 deaths annually .
Most of these tumors are squamous cell carcinomas, but melanoma, sarcoma, adenocarcinoma, and other histologic types also occur (table 1). Although primary vaginal cancer is rare, metastatic disease to the vagina or local extension from adjacent gynecologic structures is not uncommon. As a result, the majority of vaginal malignancies are metastatic, often arising from the endometrium, cervix, vulva, ovary, breast, rectum, and kidney [2-5]. Vaginal metastases may occur by direct extension (eg, cervix, vulva, endometrium) or by lymphatic or hematogenous spread (eg, breast, ovary, kidney).
The clinical manifestations, evaluation, and therapy of invasive vaginal cancer are reviewed here. Vaginal intraepithelial neoplasia is discussed elsewhere. (See "Vaginal intraepithelial neoplasia".)
EPIDEMIOLOGY AND RISK FACTORS
Approximately 1 in 100,000 women will be diagnosed with in situ or invasive vaginal cancer (typically of squamous cell histology) [6,7]. The mean age at diagnosis of squamous cell carcinoma, the most common histologic type of vaginal cancer, is approximately 60 years, although the disease is seen occasionally in women in their 20s and 30s. Squamous carcinoma is more common as the age of the patient increases .
Most cases of vaginal cancer are likely mediated by human papillomavirus (HPV) infection, as with cervical cancer . In a case-control study of 156 women with in situ or invasive vaginal cancer, over 50 percent were positive for antibodies to HPV subtypes 16 or 18 . Thus, vaginal cancer has the same risk factors as cervical neoplasia: multiple lifetime sexual partners, early age at first intercourse, and being a current smoker [9,10].
- Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin 2015; 65:5.
- Dunn LJ, Napier JG. Primary carcinoma of the vagina. Am J Obstet Gynecol 1966; 96:1112.
- WAY S. Vaginal metastases of carcinoma of the body of the uterus. J Obstet Gynaecol Br Emp 1951; 58:558.
- Bergman F. Carcinoma of the ovary. A clinicopathological study of 86 autopsied cases with special reference to mode of spread. Acta Obstet Gynecol Scand 1966; 45:211.
- Nerdrum TA. Vaginal metastasis of hypernephroma. Report of three cases. Acta Obstet Gynecol Scand 1966; 45:515.
- Shah CA, Goff BA, Lowe K, et al. Factors affecting risk of mortality in women with vaginal cancer. Obstet Gynecol 2009; 113:1038.
- Gadducci A, Fabrini MG, Lanfredini N, Sergiampietri C. Squamous cell carcinoma of the vagina: natural history, treatment modalities and prognostic factors. Crit Rev Oncol Hematol 2015; 93:211.
- Alemany L, Saunier M, Tinoco L, et al. Large contribution of human papillomavirus in vaginal neoplastic lesions: a worldwide study in 597 samples. Eur J Cancer 2014; 50:2846.
- Daling JR, Madeleine MM, Schwartz SM, et al. A population-based study of squamous cell vaginal cancer: HPV and cofactors. Gynecol Oncol 2002; 84:263.
- 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.
- 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.
- Strander B, Andersson-Ellström A, Milsom I, Sparén P. Long term risk of invasive cancer after treatment for cervical intraepithelial neoplasia grade 3: population based cohort study. BMJ 2007; 335:1077.
- Kirkbride P, Fyles A, Rawlings GA, et al. Carcinoma of the vagina--experience at the Princess Margaret Hospital (1974-1989). Gynecol Oncol 1995; 56:435.
- Choo YC, Anderson DG. Neoplasms of the vagina following cervical carcinoma. Gynecol Oncol 1982; 14:125.
- Herbst AL, Ulfelder H, Poskanzer DC. Adenocarcinoma of the vagina. Association of maternal stilbestrol therapy with tumor appearance in young women. N Engl J Med 1971; 284:878.
- Livingston RC. Primary Carcinoma of the Vagina, Thomas CC (Ed), Springfield, IL 1950.
- Underwood PB Jr, Smith RT. Carcinoma of the vagina. JAMA 1971; 217:46.
- Pride GL, Schultz AE, Chuprevich TW, Buchler DA. Primary invasive squamous carcinoma of the vagina. Obstet Gynecol 1979; 53:218.
- Gallup DG, Talledo OE, Shah KJ, Hayes C. Invasive squamous cell carcinoma of the vagina: a 14-year study. Obstet Gynecol 1987; 69:782.
- Hiniker SM, Roux A, Murphy JD, et al. Primary squamous cell carcinoma of the vagina: prognostic factors, treatment patterns, and outcomes. Gynecol Oncol 2013; 131:380.
- Di Donato V, Bellati F, Fischetti M, et al. Vaginal cancer. Crit Rev Oncol Hematol 2012; 81:286.
- Taylor MB, Dugar N, Davidson SE, Carrington BM. Magnetic resonance imaging of primary vaginal carcinoma. Clin Radiol 2007; 62:549.
- Gardner CS, Sunil J, Klopp AH, et al. Primary vaginal cancer: role of MRI in diagnosis, staging and treatment. Br J Radiol 2015; 88:20150033.
- Lamoreaux WT, Grigsby PW, Dehdashti F, et al. FDG-PET evaluation of vaginal carcinoma. Int J Radiat Oncol Biol Phys 2005; 62:733.
- Creasman WT, Phillips JL, Menck HR. The National Cancer Data Base report on cancer of the vagina. Cancer 1998; 83:1033.
- Ikenberg H, Runge M, Göppinger A, Pfleiderer A. Human papillomavirus DNA in invasive carcinoma of the vagina. Obstet Gynecol 1990; 76:432.
- Isaacs JH. Verrucous carcinoma of the female genital tract. Gynecol Oncol 1976; 4:259.
- Herbst AL, Scully RE. Adenocarcinoma of the vagina in adolescence. A report of 7 cases including 6 clear-cell carcinomas (so-called mesonephromas). Cancer 1970; 25:745.
- Hanselaar AG, Van Leusen ND, De Wilde PC, Vooijs GP. Clear cell adenocarcinoma of the vagina and cervix. A report of the Central Netherlands Registry with emphasis on early detection and prognosis. Cancer 1991; 67:1971.
- Verloop J, Rookus MA, van Leeuwen FE. Prevalence of gynecologic cancer in women exposed to diethylstilbestrol in utero. N Engl J Med 2000; 342:1838.
- Melnick S, Cole P, Anderson D, Herbst A. Rates and risks of diethylstilbestrol-related clear-cell adenocarcinoma of the vagina and cervix. An update. N Engl J Med 1987; 316:514.
- Troisi R, Hatch EE, Titus-Ernstoff L, et al. Cancer risk in women prenatally exposed to diethylstilbestrol. Int J Cancer 2007; 121:356.
- Senekjian EK, Frey KW, Anderson D, Herbst AL. Local therapy in stage I clear cell adenocarcinoma of the vagina. Cancer 1987; 60:1319.
- Senekjian EK, Frey KW, Stone C, Herbst AL. An evaluation of stage II vaginal clear cell adenocarcinoma according to substages. Gynecol Oncol 1988; 31:56.
- Frank SJ, Deavers MT, Jhingran A, et al. Primary adenocarcinoma of the vagina not associated with diethylstilbestrol (DES) exposure. Gynecol Oncol 2007; 105:470.
- Hilgers RD, Malkasian GD Jr, Soule EH. Embryonal rhabdomyosarcoma (botryoid type) of the vagina. A clinicopathologic review. Am J Obstet Gynecol 1970; 107:484.
- Andrassy RJ, Wiener ES, Raney RB, et al. Progress in the surgical management of vaginal rhabdomyosarcoma: a 25-year review from the Intergroup Rhabdomyosarcoma Study Group. J Pediatr Surg 1999; 34:731.
- DeMatos P, Tyler D, Seigler HF. Mucosal melanoma of the female genitalia: a clinicopathologic study of forty-three cases at Duke University Medical Center. Surgery 1998; 124:38.
- Frumovitz M, Etchepareborda M, Sun CC, et al. Primary malignant melanoma of the vagina. Obstet Gynecol 2010; 116:1358.
- Pandey M, Mathew A, Abraham EK, et al. Primary malignant melanoma of the mucous membranes. Eur J Surg Oncol 1998; 24:303.
- Weinstock MA. Malignant melanoma of the vulva and vagina in the United States: patterns of incidence and population-based estimates of survival. Am J Obstet Gynecol 1994; 171:1225.
- FIGO Committee on Gynecologic Oncology. Current FIGO staging for cancer of the vagina, fallopian tube, ovary, and gestational trophoblastic neoplasia. Int J Gynaecol Obstet 2009; 105:3.
- Benedet JL, Bender H, Jones H 3rd, et al. FIGO staging classifications and clinical practice guidelines in the management of gynecologic cancers. FIGO Committee on Gynecologic Oncology. Int J Gynaecol Obstet 2000; 70:209.
- Hacker NF, Eifel PJ. Vaginal cancer. In: Berek and Hacker's Gynecologic Oncology, 6th ed, Berek JS, Hacker NF. (Eds), Lippincott Williams & Wilkins, Philadelphia 2015. p.608.
- Lian J, Dundas G, Carlone M, et al. Twenty-year review of radiotherapy for vaginal cancer: an institutional experience. Gynecol Oncol 2008; 111:298.
- Stock RG, Chen AS, Seski J. A 30-year experience in the management of primary carcinoma of the vagina: analysis of prognostic factors and treatment modalities. Gynecol Oncol 1995; 56:45.
- Hacker NF, Eifel PJ, van der Velden J. Cancer of the vagina. Int J Gynaecol Obstet 2012; 119 Suppl 2:S97.
- Tjalma WA, Monaghan JM, de Barros Lopes A, et al. The role of surgery in invasive squamous carcinoma of the vagina. Gynecol Oncol 2001; 81:360.
- Stock RG, Mychalczak B, Armstrong JG, et al. The importance of brachytherapy technique in the management of primary carcinoma of the vagina. Int J Radiat Oncol Biol Phys 1992; 24:747.
- Tran PT, Su Z, Lee P, et al. Prognostic factors for outcomes and complications for primary squamous cell carcinoma of the vagina treated with radiation. Gynecol Oncol 2007; 105:641.
- Frank SJ, Jhingran A, Levenback C, Eifel PJ. Definitive radiation therapy for squamous cell carcinoma of the vagina. Int J Radiat Oncol Biol Phys 2005; 62:138.
- Grigsby PW. Vaginal cancer. Curr Treat Options Oncol 2002; 3:125.
- Dalrymple JL, Russell AH, Lee SW, et al. Chemoradiation for primary invasive squamous carcinoma of the vagina. Int J Gynecol Cancer 2004; 14:110.
- Roberts WS, Hoffman MS, Kavanagh JJ, et al. Further experience with radiation therapy and concomitant intravenous chemotherapy in advanced carcinoma of the lower female genital tract. Gynecol Oncol 1991; 43:233.
- Samant R, Lau B, E C, et al. Primary vaginal cancer treated with concurrent chemoradiation using Cis-platinum. Int J Radiat Oncol Biol Phys 2007; 69:746.
- Miyamoto DT, Viswanathan AN. Concurrent chemoradiation for vaginal cancer. PLoS One 2013; 8:e65048.
- Tewari KS, Cappuccini F, Puthawala AA, et al. Primary invasive carcinoma of the vagina: treatment with interstitial brachytherapy. Cancer 2001; 91:758.
- Reddy S, Saxena VS, Reddy S, et al. Results of radiotherapeutic management of primary carcinoma of the vagina. Int J Radiat Oncol Biol Phys 1991; 21:1041.
- Spirtos NM, Doshi BP, Kapp DS, Teng N. Radiation therapy for primary squamous cell carcinoma of the vagina: Stanford University experience. Gynecol Oncol 1989; 35:20.
- Perez CA, Grigsby PW, Garipagaoglu M, et al. Factors affecting long-term outcome of irradiation in carcinoma of the vagina. Int J Radiat Oncol Biol Phys 1999; 44:37.
- Benedetti Panici P, Bellati F, Plotti F, et al. Neoadjuvant chemotherapy followed by radical surgery in patients affected by vaginal carcinoma. Gynecol Oncol 2008; 111:307.
- Rubin SC, Young J, Mikuta JJ. Squamous carcinoma of the vagina: treatment, complications, and long-term follow-up. Gynecol Oncol 1985; 20:346.
- Chambers SK, Chambers JT, Kier R, Peschel RE. Sequelae of lateral ovarian transposition in irradiated cervical cancer patients. Int J Radiat Oncol Biol Phys 1991; 20:1305.
- Damewood MD, Hesla HS, Lowen M, Schultz MJ. Induction of ovulation and pregnancy following lateral oophoropexy for Hodgkin's disease. Int J Gynaecol Obstet 1990; 33:369.
- Al-Kurdi M, Monaghan JM. Thirty-two years experience in management of primary tumours of the vagina. Br J Obstet Gynaecol 1981; 88:1145.
- Berek JS, Hacker NF, Lagasse LD. Vaginal reconstruction performed simultaneously with pelvic exenteration. Obstet Gynecol 1984; 63:318.
- Benson C, Soisson AP, Carlson J, et al. Neovaginal reconstruction with a rectus abdominis myocutaneous flap. Obstet Gynecol 1993; 81:871.
- Thigpen JT, Blessing JA, Homesley HD, et al. Phase II trial of cisplatin in advanced or recurrent cancer of the vagina: a Gynecologic Oncology Group Study. Gynecol Oncol 1986; 23:101.
- Belinson JL, Stewart JA, Richards AL, McClure M. Bleomycin, vincristine, mitomycin-C, and cisplatin in the management of gynecological squamous cell carcinomas. Gynecol Oncol 1985; 20:387.
- Umesaki N, Kawamura N, Tsujimura A, et al. Stage II vaginal cancer responding to chemotherapy with irinotecan and cisplatin: a case report. Oncol Rep 1999; 6:123.
- Kim DS, Moon H, Hwang YY, Park MI. Histologic disappearance of locally advanced vaginal cancer after combination chemotherapy. Gynecol Oncol 1990; 38:144.
- Salani R, Backes FJ, Fung MF, et al. Posttreatment surveillance and diagnosis of recurrence in women with gynecologic malignancies: Society of Gynecologic Oncologists recommendations. Am J Obstet Gynecol 2011; 204:466.
- Andreasson B, Moth I, Jensen SB, Bock JE. Sexual function and somatopsychic reactions in vulvectomy-operated women and their partners. Acta Obstet Gynecol Scand 1986; 65:7.
- Green MS, Naumann RW, Elliot M, et al. Sexual dysfunction following vulvectomy. Gynecol Oncol 2000; 77:73.
- Nori D, Hilaris BS, Stanimir G, Lewis JL Jr. Radiation therapy of primary vaginal carcinoma. Int J Radiat Oncol Biol Phys 1983; 9:1471.
- Brady LW, Perez CA, Bedwinek JM. Failure patterns in gynecologic cancer. Int J Radiat Oncol Biol Phys 1986; 12:549.
- Hellman K, Lundell M, Silfverswärd C, et al. Clinical and histopathologic factors related to prognosis in primary squamous cell carcinoma of the vagina. Int J Gynecol Cancer 2006; 16:1201.
- Beller U, Sideri M, Maisonneuve P, et al. Carcinoma of the vagina. J Epidemiol Biostat 2001; 6:141.
- EPIDEMIOLOGY AND RISK FACTORS
- CLINICAL MANIFESTATIONS
- DIAGNOSTIC EVALUATION
- Physical examination
- Vaginal cytology
- Vaginal colposcopy
- Vaginal biopsy
- Imaging studies
- DIFFERENTIAL DIAGNOSIS
- Squamous cell carcinoma
- Routes of spread
- Stage I tumors
- - Surgery
- - Radiation therapy
- Stage II to IV tumors
- - Chemoradiation
- - Radiation therapy
- - Is there a role for surgery?
- - Neoadjuvant therapy
- TREATMENT-RELATED COMPLICATIONS
- RECURRENT DISEASE
- POSTTREATMENT SURVEILLANCE
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS