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This summary addresses squamous cell cancer of the vulva and vulvar intraepithelial neoplasias (VIN), some of which are thought to be precursors to invasive squamous cell cancers.
The labia majora are the most common sites of vulvar carcinoma involvement and account for about 50% of cases. The labia minora account for 15% to 20% of vulvar carcinoma cases. The clitoris and Bartholin glands are less frequently involved. Lesions are multifocal in about 5% of cases. More than 90% of invasive vulvar cancers are squamous cell carcinomas.
Incidence and Mortality
Vulvar cancer accounts for about 4% of cancers of the female genital system in the United States.
Estimated new cases and deaths from vulvar cancer in the United States in 2019:
The vulva is the area immediately external to the vagina, including the mons pubis, labia, clitoris, Bartholin glands, and perineum.
Anatomy of the vulva. The vulva includes the mons pubis, clitoris, urethral opening, inner and outer lips of the vagina, vaginal opening, and perineum.
Increasing age is the most important risk factor for most cancers. Other risk factors associated with vulvar cancer include the following:
HPV-associated VIN, termed usual-type VIN when high grades 2 and 3, is most common in women younger than 50 years, whereas non-HPV VIN, termed differentiated-type VIN when high grade 3, is most common in older women.[5,6]
The former lesion-type VIN grade 1 is no longer classified as a true VIN.[5,6] The HPV-related basaloid and warty types are associated with VIN. About 75% to 100% of basaloid and warty carcinomas harbor HPV infection. In addition to the much higher prevalence of HPV in these subtypes than in the keratinizing subtypes, the basaloid and warty subtypes also share many common risk factors with cervical cancers, including the following:
(Refer to the PDQ summary on Cervical Cancer Treatment for more information.)
Women with VIN may not present with symptoms at diagnosis.
Possible signs and symptoms of invasive squamous cell cancers of the vulva include the following:
Diagnostic and Staging Evaluation
The following procedures may be used to diagnose and stage vulvar cancer:
Prognosis depends on the pathologic status of the inguinal lymph nodes and whether spread to adjacent structures has occurred. In patients with operable disease without lymph node involvement, the overall survival (OS) rate is 90%; however, in patients with nodal involvement, the 5-year OS rate is approximately 50% to 60%.
The size of the primary tumor is less important in defining prognosis.
Follow-up After Treatment
Invasive and preinvasive neoplasms of the vulva may be HPV-induced and the carcinogenic effect may be widespread in the vulvar epithelium. As a result, patients are monitored regularly for signs or symptoms of recurrence.
The histologic classification of vulvar disease and precursor lesions of cancer of the vulva was developed by the International Society for the Study of Vulvovaginal Disease (ISSVD).
Non-neoplastic epithelial disorders of vulvar skin and mucosa
Vulvar intraepithelial neoplasia (VIN)
Paget disease of the vulva
Staging evaluation for vulvar cancer includes the following, as needed:
Suspected bladder or rectal involvement must be confirmed by biopsy.
The Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) Staging
FIGO and the American Joint Committee on Cancer have designated staging to define vulvar cancer; the FIGO system is most commonly used.[1,2] Stage is based on pathology staging at the time of surgery or before any radiation or chemotherapy, if they are the initial treatment modalities.
The staging system does not apply to malignant melanoma of the vulva, which is staged like melanoma of the skin.
Grade is reported in registry systems and may differ between systems; a two-, three-, or four-grade system may be applied. If not specified, the following system is generally used:
Overall, about 30% of patients with operable disease have lymph node spread. The pattern of spread is influenced by the histology. Risk factors for lymph node metastasis include the following:[4,5,6,7,8]
Well-differentiated lesions tend to spread along the surface with minimal invasion, whereas anaplastic lesions are more likely to be deeply invasive. Spread beyond the vulva is either to adjacent organs such as the vagina, urethra, and anus, or via the lymphatics to the inguinal and femoral lymph nodes, followed by the deep pelvic nodes. Hematogenous spread appears to be uncommon.
Standard primary treatment for vulvar cancer is surgery. Radiation therapy is also given to patients with stage III or IV disease.[1,2,3] Newer strategies have integrated surgery, radiation therapy, and chemotherapy and tailor the treatment to the extent of clinical and pathologic disease. Patterns of practice in combining these treatments vary.
Because there are few patients with advanced disease (stages III and IV), only limited data are available on treatment efficacy in this setting, and there is no standard chemotherapy regimen for these patients. Physicians may offer eligible patients with stage III or IV disease participation in clinical trials.
Information about ongoing clinical trials is available from the NCI website.
Since the 1980s, the trend of surgical resection in patients with vulvar cancer has been toward more limited surgery, often combined with radiation therapy to minimize morbidity. In tumors clinically confined to the vulva or perineum, radical local excision with a margin of at least 1 cm has generally replaced radical vulvectomy; separate incision has replaced en bloc inguinal lymph node dissection; ipsilateral inguinal node dissection has replaced bilateral dissection for laterally localized tumors; and femoral lymph node dissection has been omitted in many cases.[2,5,6,7] However, the different surgical techniques have not been directly compared in randomized controlled trials. In addition, nonrandomized studies lack uniform staging definitions and clear descriptions of lymph node dissection or ancillary radiation.[Levels of evidence: 3iiiDii and 3iiiDiv] The evidence base is therefore limited.
Sentinel lymph node dissection (SLND)
Another strategy to minimize the morbidity incurred by groin lymph node dissection in patients with early clinical-stage disease is SLND, reserving groin dissection for those with metastases to the sentinel node(s).
SLND may be useful when performed by a surgeon experienced in the procedure, and it may avoid the need for full groin lymph node dissection or radiation in patients with clinically nonsuspicious lymph nodes.
Radical radiation therapy can be used for patients unable to tolerate surgery or when surgery is not an option because of the site or extent of disease.[10,11,12,13]
Groin lymph node metastases are present in approximately 20% to 35% of patients with tumors clinically confined to the vulva and with clinically negative nodes.[9,14] Lymph node dissection is traditionally part of the primary surgical therapy in all but the smallest tumors. Some investigators recommend radiation therapy as a means to avoid the morbidity of lymph node dissection, but it is not clear whether radiation therapy can achieve the same local control rates or survival rates as lymph node dissection in early-stage disease.
Localized node-negative disease
A randomized trial to address the efficacy of radiation therapy in patients with clinically localized vulvar cancer has been reported.[14,15] In that study, women with disease clinically confined to the vulva, who did not have clinically suspicious groin lymph node metastases, underwent radical vulvectomy followed by either groin radiation (50 Gy at 2 Gy per fraction) or groin dissection (plus groin radiation if nodes were pathologically involved). Although the planned accrual was 300 patients, the study was stopped after 58 women were randomly assigned to it because of worse outcomes in the radiation therapy arm.
In summary, the trial was stopped prematurely, and little can be said about the relative efficacy of the two treatment approaches.
Pelvic node–positive disease
Pelvic radiation therapy has been compared with pelvic node resection in the setting of documented groin node–positive disease.
Evidence (pelvic node resection vs. pelvic radiation therapy):
There is no standard chemotherapy for vulvar cancer, and reports describing the use of this modality in the setting of metastatic or recurrent disease are anecdotal.
Extrapolating from regimens used for anal or cervical squamous cell cancers, chemotherapy has been studied in combination with radiation in the neoadjuvant setting or as primary therapy in advanced disease. Chemotherapy regimens have included various combinations of fluorouracil (5-FU), cisplatin, mitomycin-C, or bleomycin.
There is no clear evidence of improvement in survival or palliation. Given the advanced age and comorbidities of many patients with advanced or recurrent vulvar cancer, patient tolerance is a major consideration in the use of these agents.
Systemic treatment for inoperable patients
A systematic review of the use of neoadjuvant chemoradiation therapy in patients who were considered inoperable or who would have required extensive surgery, such as pelvic exenteration, colostomy, or urinary diversion, revealed no randomized trials. Five nonrandomized studies that met the inclusion criteria of neoadjuvant chemoradiation therapy administered in this population with an intent to permit curative surgery were reviewed.[18,19,20,21,22] The five studies used four different chemoradiation therapy schedules and different radiation therapy dose-fractionation techniques. In the four studies using 5-FU with either cisplatin or mitomycin-C, the operability rate after chemoradiation therapy ranged from 63% to 92%.[18,19,20,21] In the one study using bleomycin, the operability rate was only 20%.
In summary, there is evidence that neoadjuvant chemoradiation therapy with 5-FU plus either cisplatin or mitomycin-C may convert patients to a more operable status, but the evidence base is limited by study design. In addition to a paucity of randomized trials, interpretation of these studies is complicated by the lack of a standard definition of operability.[Level of evidence: 3iiiDiv] Treatment-related toxicity is substantial.
Systemic treatment for operable patients
There is limited evidence regarding the use of neoadjuvant chemoradiation therapy in advanced operable vulvar cancer, and the available data do not suggest an advantage to this approach. A systematic review found only one randomized trial that addressed this issue, and it was published only in abstract form.[4,23] In that trial, 68 patients with advanced vulvar cancer (T2* >4 cm, T3*, any case with positive lymph nodes) were randomly assigned to either receive preoperative neoadjuvant radiation therapy (50 Gy) concomitantly with 5-FU and mitomycin-C or primary surgery. Neoadjuvant therapy–related serious toxicity was high (13 of 24 patients; 10 patients had wound diastasis). After a mean follow-up of 42 months, the 5-year OS rate was 30% in the neoadjuvant chemoradiation therapy arm and 49% in the primary surgery arm (RRdeath, 1.39; 95% CI, 0.94–2.06; P = .19).[4,23][Level of evidence 1iiA] *T2 is defined as tumor confined to the vulva and/or perineum, more than 2 cm in greatest dimension, and T3 is defined as tumor that invades any of the following: the lower urethra, vagina, or anus.
Standard Treatment Options for VIN
Standard treatment options for VIN include the following:
Traditionally, there were three grades of VIN, however, there is little evidence that all three grades are part of the same biologic continuum or that grade 1 is even a cancer precursor. In 2004, the International Society for the Study of Vulvovaginal Disease (ISSVD) changed its terminology, reserving the designation VIN for two categories of lesions based on morphologic appearance. In 2015, the ISSVD developed terminology for vulvar squamous intraepithelial lesions (SIL), which includes the following:
High-grade VIN is usually managed with active therapy because of a higher risk for progression to invasive disease. Estimates of progression rates are imprecise. A systematic literature review that included 88 untreated patients with VIN 3 reported a 9% progression rate (8 of 88 patients) to invasive vulvar cancer during 12 to 96 months of observation. In the same review, the spontaneous regression rate was 1.2%, all of which occurred in women younger than 35 years. However, in a single-center study, 10 of 63 (16%) untreated women with VIN 2 or VIN 3 progressed to invasive cancer after a mean of 3.9 years.
VIN lesions may be multifocal or confluent and extensive. It is important to perform multiple biopsies in treatment planning to exclude occult invasive disease. VIN located in nonhairy areas can be considered an epithelial disease; however, VIN found in hairy sites usually involves the pilosebaceous apparatus and requires a greater depth of excision because it can track along hair roots.
The principal treatment approach is surgery, but there is no consensus on the optimal surgical procedure. The goal is to remove or destroy the entire VIN lesion while preserving vulvar anatomy and function. Simple vulvectomy yields a 5-year survival rate of nearly 100% but is seldom indicated. Other more-limited surgical procedures, including separate excision of multiple lesions, are less deforming. The choice of treatment depends on the extent of the disease and the experience of the treating physician. There are no reliable data comparing the efficacy and safety of the various surgical approaches.
A systematic literature review identified only a single randomized trial comparing any of the surgical approaches. In that trial, 30 women with high-grade VIN were randomly assigned to either receive CO2 laser ablation or ultrasound surgical aspiration. There were no statistically significant differences in disease recurrence, painful dysuria or burning, adhesions, or eschar formation between the two treatments after 1 year of follow-up. Scarring was observed in 5 of 16 women treated with laser ablation and 0 of 14 women treated with ultrasound surgical aspiration (P < .01), but consequences of the scarring on sexual function or quality of life were not reported.[Level of evidence 1iiDii] The trial was too small to draw reliable conclusions about the relative efficacy of these surgical techniques. The remainder of the surgical literature is derived from case series and is prone to important study biases.[Level of evidence 3iiiD]
Whatever procedure is used, patients are at substantial risk of recurrence, particularly when the lesions are high grade or multifocal. The most common sites of recurrence are the perianal skin, presacral area, and clitoral hood. About 4% of patients treated for VIN subsequently develop invasive cancer.[14,15]
Among women with high-grade VIN, substantial response rates and acceptable tolerability were reported for topical imiquimod 5%, an immune-response modifier with activity in human papillomavirus types 6- and 11-associated vulvar condylomata.
Other nonsurgical interventions
Nonsurgical approaches have been studied because of the physical and psychosexual morbidity associated with many vulvar surgical procedures. Some of these approaches, including topical fluorouracil, recombinant interferon gamma, bleomycin, and trinitrochlorobenzene, have been largely abandoned because of high recurrence rates or intolerable local side effects, such as pain, irritation, and ulceration.[8,16]
Photodynamic therapy, using topically applied 5-aminolevulinic acid as the sensitizing agent for 635 nm laser light, has also been studied. However, data are limited to small case series with variable response rates.[17,18][Level of evidence: 3iiiDiv]
Current Clinical Trials
Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.
Standard Treatment Options for Stages I and II Vulvar Cancer
Standard treatment options for stage I and stage II vulvar cancer include the following:
Radical local excision with ipsilateral or bilateral inguinal and femoral lymph node dissection may be indicated. For stage I microinvasive lesions (<1 mm invasion) with no associated severe vulvar dystrophy, a wide (1 cm margin) excision (without lymph node dissection) may be done. For all other stage I lesions, if well lateralized, without diffuse severe dystrophy, and with clinically negative nodes, a radical local excision with complete unilateral lymphadenectomy may be done. Candidates for this procedure should have lesions 2 cm or smaller in diameter with 5 mm or less invasion, no capillary-lymphatic space invasion, and clinically uninvolved nodes.[2,3]
For stage II disease, large T2* tumors may require modified radical vulvectomy or radical vulvectomy.*T2 is defined as tumor confined to the vulva and/or perineum, more than 2 cm in greatest dimension.
For both stage I and stage II disease, radical local excision and sentinel node dissection is indicated and groin dissection is reserved for those with metastasis to the sentinel node(s).
Surgery and radiation therapy
Some investigators recommend radical excision and groin nodal radiation therapy as a means to avoid the morbidity of lymph node dissection. However, it is not clear whether radiation therapy can achieve the same local control rates or survival rates as lymph node dissection in early-stage disease. A randomized trial to address this issue in patients with clinically localized vulvar disease was stopped early as a result of early emergence of worse outcomes in the radiation therapy arm.[6,7] For stage II disease, adjuvant local radiation therapy may be indicated for surgical margins smaller than 8 mm, capillary-lymphatic space invasion, and thickness greater than 5 mm.[8,9]
Radiation therapy alone
For patients unable to tolerate radical surgery or deemed unsuitable for surgery because of the site or extent of disease, radical radiation therapy may be associated with favorable survival.[10,11,12,13]
Standard Treatment Options for Stage III Vulvar Cancer
Standard treatment options for stage III vulvar cancer include the following:
Surgery with or without radiation therapy
Modified radical or radical vulvectomy with inguinal and femoral lymphadenectomy is the standard therapy. Nodal involvement is a key determinant of survival. Radiation therapy is given to patients with large primary lesions and narrow margins. Radiation therapy to the pelvis and groin is given if inguinal lymph nodes are positive. Radiation therapy to the pelvis and groin is usually given if two or more groin nodes are involved.[2,3]
Localized adjuvant radiation therapy consisting of 45 Gy to 50 Gy may also be indicated when there is capillary-lymphatic space invasion and a thickness of greater than 5 mm, particularly if the nodes are involved.
Radiation therapy or chemoradiation therapy followed by surgery
Preoperative neoadjuvant radiation therapy or chemoradiation therapy may be used to improve operability and even decrease the extent of surgery required.[4,5,6,7,8,9,10]
Radiation therapy with or without chemotherapy
For patients unable to tolerate radical surgery or deemed unsuitable for surgery because of the site or extent of disease, radical radiation therapy may be associated with long-term survival.[11,12] Some physicians prefer to add concurrent fluorouracil (5-FU) or 5-FU and cisplatin.[1,13]
Standard Treatment Options for Stage IVA Vulvar Cancer
Standard treatment options for stage IVA vulvar cancer include the following:
Radical vulvectomy and pelvic exenteration may be indicated for patients with stage IVA vulvar cancer.
Surgery followed by radiation therapy may be done for large resected lesions with narrow margins. Localized adjuvant radiation therapy consisting of 45 Gy to 50 Gy may also be indicated when there is capillary-lymphatic space invasion and thickness greater than 5 mm. Radiation therapy to the pelvis and groin is given if two or more groin lymph nodes are involved.[2,3]
Neoadjuvant radiation therapy or chemoradiation therapy of large primary lesions (to improve operability) may be done, followed by radical surgery.[4,5,6,7,8,9,10]
For patients unable to tolerate radical vulvectomy or who are deemed unsuitable for surgery because of the site or extent of disease, radical radiation therapy may be associated with long-term survival.[11,12] When radiation therapy is used for primary definitive treatment of vulvar cancer, some physicians prefer to add concurrent fluorouracil (5-FU) or 5-FU and cisplatin.[1,13,14,15,16,17]
Treatment Options for Stage IVB Vulvar Cancer
There is no standard treatment approach in the management of stage IVB vulvar cancer.
Local therapy must be individualized depending on the extent of local and metastatic disease.
There is no standard chemotherapy for metastatic disease, and reports describing the use of this modality are anecdotal. However, by largely extrapolating from regimens used for anal or cervical cancer, chemotherapy has been studied. Regimens have included various combinations of fluorouracil, cisplatin, mitomycin-C, or bleomycin.[1,2,3] Given the advanced age and comorbidity of many patients with advanced or recurrent vulvar cancer, patient tolerance is a major consideration in the use of these agents.
Treatment Options for Recurrent Vulvar Cancer
Treatment options for recurrent vulvar cancer include the following:
Treatment and outcome depend on the site and extent of recurrence. Radical excision of localized recurrence may be considered if technically feasible. Palliative radiation therapy is used for some patients. Radiation therapy with or without chemotherapy may be associated with substantial disease-free periods in some patients with a small local recurrence.[1,4,5] When local recurrence occurs more than 2 years after primary treatment, a combination of radiation therapy and surgery may result in a 5-year survival rate of greater than 50%.[6,7]
The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.
This summary was comprehensively reviewed, extensively revised, and reformatted.
This summary is written and maintained by the PDQ Adult Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® - NCI's Comprehensive Cancer Database pages.
Purpose of This Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of vulvar cancer. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.
Reviewers and Updates
This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).
Board members review recently published articles each month to determine whether an article should:
Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.
The lead reviewers for Vulvar Cancer Treatment are:
Any comments or questions about the summary content should be submitted to Cancer.gov through the NCI website's Email Us. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.
Levels of Evidence
Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Adult Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.
Permission to Use This Summary
PDQ is a registered trademark. Although the content of PDQ documents can be used freely as text, it cannot be identified as an NCI PDQ cancer information summary unless it is presented in its entirety and is regularly updated. However, an author would be permitted to write a sentence such as "NCI's PDQ cancer information summary about breast cancer prevention states the risks succinctly: [include excerpt from the summary]."
The preferred citation for this PDQ summary is:
PDQ® Adult Treatment Editorial Board. PDQ Vulvar Cancer Treatment. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/types/vulvar/hp/vulvar-treatment-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389203]
Images in this summary are used with permission of the author(s), artist, and/or publisher for use within the PDQ summaries only. Permission to use images outside the context of PDQ information must be obtained from the owner(s) and cannot be granted by the National Cancer Institute. Information about using the illustrations in this summary, along with many other cancer-related images, is available in Visuals Online, a collection of over 2,000 scientific images.
Based on the strength of the available evidence, treatment options may be described as either "standard" or "under clinical evaluation." These classifications should not be used as a basis for insurance reimbursement determinations. More information on insurance coverage is available on Cancer.gov on the Managing Cancer Care page.
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Last Revised: 2019-12-31
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