Vulvar carcinoma encompasses any malignancy that arises in the skin, glands, or underlying stroma of the perineum, including the mons, labia minora, labia majora, Bartholin glands, or clitoris. (See the image below.) Tumors can also arise in ectopic breast tissue that can be located in the vulva along the milk line. Metastatic tumors to the vulva infrequently occur. For related information, see the Medscape Reference article Malignant Vulvar Lesions.
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A large T2 carcinoma of the vulva crossing the midline and involving the clitoris. (Photograph courtesy of Tom Wilson)
Signs and symptoms
The majority of patients present with a single vulvar lesion. Patients may complain of vulvar pruritus, pain, or irritation, although many patients are asymptomatic. Patients with advanced disease can present with enlarged inguinal lymph nodes, lower-extremity edema, or rectal bleeding.
See Presentation for more detail.
Diagnosis
Patients presenting with vulvar complaints should have a complete pelvic examination, including palpation for enlarged inguinal lymph nodes, vaginal speculum examination, and bimanual pelvic examination. A biopsy should be performed when any discrete lesion of the vulva is detected.
Imaging studies are useful to rule out metastatic disease for patients with large vulvar lesions and/or palpable inguinal lymph nodes. Positron emission tomography (PET) scanning is the most accurate modality to detect pelvic or para-aortic adenopathy in patients with vulvar cancer.[1]
See Workup for more detail.
Treatment
Resection of the primary lesion is the treatment of choice for vulvar carcinoma. Patients with inoperable primary tumors or fixed inguinal lymph nodes are candidates for preoperative treatment with chemotherapy and radiation.
Patients with vulvar cancer, in the early part of the 20th century, usually died of disease. The overall survival rate for vulvar cancer after simple surgical excision was less than 25%. Attempts to improve outcomes for patients with vulvar cancer by performing more radical surgery were first described by Basset in 1912.[2] Way described an improved survival rate using an en bloc dissection radical vulvectomy with an inguinal and pelvic lymphadenectomy.[3] The Bassett-Way operation resulted in a 5-year survival rate of 74% as reported by Morley.[4] This success rate convinced most surgeons to use this operation for all patients with vulvar cancer regardless of tumor size. Major morbidity from this procedure included poor wound healing and chronic lymphedema.
Fred Taussig collected a large series of vulvar cancer cases from 1911-1940.[5] He initially started his series with a radical excision of the primary tumor with an en bloc dissection of the inguinal lymph nodes. Later, he modified his technique for patients with small lesions in an attempt to decrease operative morbidity. He used separate incisions for the groin dissection and the vulvar excision. This reduction in the volume of tissue removed in women with small lesions was not routinely used until Hacker reported his experience with 100 patients in 1981.[6] He reported using 3 separate incisions, as described by Taussig, for patients with clinical stage I disease. The 5-year survival rate was 97%.
Cancer of the vulva is the fourth most common malignancy of the female genital tract. The American Cancer Society estimates in 2023 there will be 6470 women diagnosed with vulvar cancer and 1670 deaths from this disease in the United States.[7]
International statistics
Unfortunately, the incidence of preinvasive disease of the vulva has almost doubled over the past decade, and this may translate into a marked increase in the incidence of invasive vulvar carcinoma in the future. Since vulvar cancer is rare and is not monitored by the World Health Organization, the global incidence of this disease is not precisely known.
The incidence of vulvar carcinoma has a bimodal peak. Currently, development of vulvar carcinoma in situ in young women is suggested to correlate to human papillomavirus (HPV) infection. In older women, the etiology of the carcinoma is attributed to chronic irritation or other poorly understood cofactors.
Risk factors
Estimates indicate that women who smoke cigarettes have a 4- to 5-fold increase in the incidence of carcinoma in situ of the vulva and a 20% increase in vulvar carcinoma. The incidence of vulvar carcinoma in situ and vulvar carcinoma is higher in women with multiple sexual partners and in women with a history of HPV infection. For women who report a history of genital warts or HPV-related disease, the relative risk for carcinoma in situ is 18.5 and for invasive cancer is 14.5.
The development of vulvar dysplasia and cancer in most patients is related to HPV infection. Certain strains of HPV are known to be more oncogenic than others. HPV types 16, 18, 31, 33, 35, 45, and 54 are more likely to be associated with cervical neoplasia and cancer and are suspected to also be responsible for vulvar cancers. The DNA from HPV 16 and 18 has been detected in up to 60% of patients with vulvar cancer.
The mechanism of HPV transformation into dysplasia and cancer is not well understood. Two gene products from HPV are known to immortalize cells in culture and are probably responsible for malignant transformation. The HPV E6 protein does have the ability to bind the host p53 protein. The HPV E7 protein binds the Rb gene product. The oncogenic viral types are thought to have a greater affinity for these cellular proteins, which would explain the increased risk of malignant transformation. Some infections may lead to integration of the viral DNA into the host, with disruption of the normal regulation of the E6 and E7 oncoproteins. This increased production of the E6 and E7 gene products could then result in oncogenic transformation.
Diagnosis of vulvar carcinoma is often delayed. Women neglect to seek treatment for an average of 6 months from the onset of symptoms. In addition, a delay in diagnosis often occurs after the patient presents to her physician. In many cases, a biopsy of the lesion is not performed until the problem fails to respond to numerous topical therapies. A biopsy should be performed when any discrete lesion of the vulva is discovered.
The most common presentation is a pruritic lesion of the vulva or a mass detected by the patient herself. However, early vulvar cancer may be asymptomatic and recognized only with careful inspection of the vulva. A biopsy should be performed on all visible lesions on the vulva. More advanced vulvar carcinomas present with bleeding, pain, or discharge.
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A large squamous cell carcinoma of the vulva. Note the small contralateral "kissing lesion" that can be seen with vulvar carcinomas. (Photograph court....
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A large T2 carcinoma of the vulva crossing the midline and involving the clitoris. (Photograph courtesy of Tom Wilson)
Choosing the proper surgical procedure for vulvar cancer is important. Patients with vulvar dysplasia can have a wide local excision. The advantage of this procedure is pathologic examination of the removed tissue. Microscopic diagnosis allows for assessment of surgical margins and assures the absence of invasive disease. Ablative procedures may be appropriate to treat dysplastic lesions if vulvar cancer can be excluded with reasonable certainty.
A women with biopsy-proven squamous cell carcinoma of the vulva is usually a candidate for surgical excision. Patients with a lesion involving the upper urethra or anus or is fixed to the pelvic bone can be treated with neoadjuvant radiation and chemotherapy prior to surgical intervention.[8] This type of therapy can allow future resection with preservation of the urethral or rectal sphincter in most cases. Radiation can also be used in an attempt to spare the clitoris.
The vulva includes all external genital structures, including the mons pubis, labia majora, labia minora, clitoris, vaginal vestibule, perineum, and supporting structures exterior to the urogenital diaphragm.
The femoral triangle is bounded by the inguinal ligament superiorly, the adductor longus medially, and the sartorius laterally. The superficial groin nodes lie above the cribriform fascia in the femoral triangle. Careful dissection generally reveals 5 vessels in the femoral triangle above the cribriform fascia, the largest of which is the saphenous vein. Often, a lateral accessory saphenous vein can be identified. The other vessels include the superficial circumflex, the superficial epigastric, and the external pudendal. Below the cribriform fascia are the deep inguinal nodes. Three to 4 nodes can be found medial to the femoral vein. The most superior of these is the sentinel node to the pelvic lymphatics and is known as the node of Cloquet.
The lymphatics of the vulva and distal third of the vagina drain into the superficial inguinal node group and travel through the deep femoral lymphatics and the node of Cloquet to the pelvic nodal groups (see image below).[9] Direct spread to the deep nodal groups without metastasis to the superficial group has been documented using lymphatic mapping. This type of direct spread is uncommon and represents fewer than 5% of cases.
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Diagram of lymphatic drainage of a lateral lesion. Most lymphatics flow through the superficial inguinal nodes, deep inguinal nodes, and the node of C....
Lymphatic mapping studies have also demonstrated that radioactive colloid injected into the vulva can accumulate more readily in the lateral external iliac nodes than in the medial group, which suggests that not all lymphatics flow to the medial pelvic nodes through the node of Cloquet. Studies suggest that 10-20% of lymphatic flow from the superficial node group travels directly to the pelvis without passage through the deep inguinal nodes. A direct pathway from the clitoris or vulva to the pelvic nodes has not been identified.
Resection of the primary lesion is the treatment of choice because few alternatives to surgery are available for vulvar carcinoma. Regional or general anesthesia can be used for this type of surgery. Patients with inoperable primary tumors or fixed inguinal lymph nodes are candidates for preoperative treatment with chemotherapy and radiation.[10] This treatment modality often reduces tumor volume and improves the chances for surgical resection. The morbidity of this regimen is substantial.[11]
Radiation alone can be used for palliation but should not be considered a curative treatment.
Overall survival for patients with vulvar carcinoma is excellent, especially in those with early-stage disease. Experience with modern treatment from the Mayo clinic shows that the overall survival rate for women with vulvar carcinoma is 75%, compared to an 89% actuarial survival rate for age-matched controls. The 5-year survival rates after surgery for vulvar cancer are as follows:
Stage I - 90%
Stage II - 81%
Stage III - 68%
Stage IV - 20%
Tantipalakorn and colleagues published their results in 121 patients with stage I and II squamous cell carcinoma in 2009. There was no difference in survival rates between patients with stage I and stage II disease. The 5-year actuarial survival for stage I disease was 97% compared with 95% for stage II disease. More than 95% of these patients were treated with vulvar-conserving surgery.[12]
The majority of patients present with a single vulvar lesion. Patients may complain of vulvar pruritus, pain, or irritation, though many patients will be asymptomatic. Patients with advanced disease can present with enlarged inguinal lymph nodes, lower-extremity edema, or rectal bleeding.
Patients presenting with vulvar complaints should have a complete pelvic examination, including palpation for enlarged inguinal lymph nodes, vaginal speculum examination, and bimanual pelvic examination. Biopsy any abnormal lesions suspicious for cancer. The usual appearance of a vulvar cancer is a raised red lesion, which is firm or friable depending on the size of the lesion.
Women with a small vulvar cancer and nonpalpable inguinal lymph nodes require little preoperative testing, except what is indicated for preoperative clearance.
Imaging studies are useful to rule out metastatic disease for patients with large vulvar lesions and/or palpable inguinal lymph nodes.
A CT scan may be useful to help evaluate nodal spread in the pelvis in women with evidence of groin node metastasis, but the sensitivity of a CT scan to help detect pelvic lymphadenopathy is approximately 30%. Positron emission tomography (PET) scanning is the most accurate modality to detect pelvic or para-aortic adenopathy in patients with vulvar cancer.[1]
Pulmonary function tests may be appropriate in women who smoke and are older than 50 years to help in perioperative management. Evaluation should also include an arterial blood gas analysis.
Colposcopy can be performed on the vulva but is more difficult than colposcopy of the cervix because of the large surface area of the vulva and the variability in premalignant lesions. Because of the keratinized skin, acetic acid should be placed for at least 5 minutes prior to colposcopy. To facilitate biopsy, EMLA (ie, eutectic mixture of local anesthetics) cream may be applied to ameliorate the pain from lidocaine injection. A punch biopsy tool can be used to take a representative sample of the vulva. A biopsy should be performed on all lesions to ensure that a cancer is not missed when multiple dysplastic lesions are present.
Squamous carcinoma is the most common pathologic type of vulvar carcinoma. Various grading systems are described and may be prognostic. Other prognostic features include confluent growth patterns and lymph vascular involvement.
Melanoma accounts for approximately 10% of vulvar cancers. The staging and treatment is similar to other melanomas. Clark defined a classification system that describes prognosis based on invasion of melanoma to certain tissue levels.[13] This system has been modified by Chung for use in vulvar melanoma.[14] Similarly, the depth of invasion, as described by Breslow, can be used to predict prognosis.[15]
Sarcoma is relatively uncommon. Subtypes include leiomyosarcoma, malignant fibrous histiocytoma, and epithelioid sarcoma. In addition, a sarcoma can arise from any structure in the vulva; including blood vessels, skeletal muscle, and fat.
Basal cell carcinoma of the vulva is uncommon, but it can occur in elderly women. As with other basal cell carcinomas, local excision is usually curative.
Verrucous carcinoma resembles condylomata acuminata and is also called a Buschke-Lowenstein giant condyloma. This type of carcinoma is locally aggressive but does not have a propensity to spread via lymphatics. These tumors are thought to be associated with HPV type 6.
Adenocarcinoma may arise in the Bartholin gland, and it represents approximately 40% of tumor types from this location. This type of tumor may attain considerable size before detection. Removal of the Bartholin gland to exclude an underlying carcinoma is indicated for recurrent Bartholin gland abscesses or cysts or if asymptomatic enlargement occurs in persons older than 50 years.
Paget's disease usually manifests as a red, raised, pruritic lesion. Histologically, the lesion is noted to contain cells with prominent nuclei and an increased amount of cytoplasm. Paget's disease has been associated with underlying adenocarcinoma of the colon or sweat glands in 15% of cases. Although Paget's disease does not metastasize, because the histologic changes often extend past the gross extent on the skin, it is known to have a high rate of local recurrence. For this reason, a clinical margin of 2 cm is recommended at the time of excision.
Other carcinomas of the vulva are rare. Tumors can occur in the apocrine sweat glands, and breast carcinoma can also develop from ectopic breast tissue contained within the milk line that extends down into the vulva.
The International Federation of Gynecology and Obstetrics (FIGO) revised staging for carcinoma of the vulva in 2021.[16] The FIGO committee used a new approach by analysis of prospective collected data.
Table 1. Staging of vulvar cancer by FIGO 2021
View Table
See Table
Table 2. Tumor Regional Lymph Node Involvement and Metastasis Categories and FIGO Stages
Neoadjuvant therapy for vulvar cancer may be considered for tumors that manifest with bowel or bladder involvement that would require extensive or exenterative surgery. The Gynecologic Oncology Group (GOG) reported its experience with a combination of cisplatin and 5-fluorouracil with hyperfractionated radiation for patients with unresectable stage III or stage IV squamous cell carcinoma of the vulva. After chemotherapy and radiation, 71 of 73 women were candidates for surgery and almost half had no visible disease. Urinary and fecal continence was preserved in all but 3 of these women.[8]
Except in the neoadjuvant setting, chemotherapy for vulvar carcinoma is palliative and often ineffective. Only bleomycin has been reported to produce a complete clinical response. In a series of 11 patients, Trope and colleagues administered bleomycin at a dose of 15 mg twice weekly and noted two complete responses (19%) and three partial responses (27%), for a total response rate of 46%.[17]
The only other agent that has been reported to be effective in recurrent vulvar cancer is doxorubicin. Deppe et al reported a partial response in 3 of 4 patients treated at a dose of 45 mg/m2.[18]
In women with locally advanced vulvar cancer, no significant differences in survival or adverse events were found when primary chemoradiation or neoadjuvant chemoradiation were compared with primary surgery. However, these findings were based on small numbers and few studies in this Cochrane review.[19] Good, quality studies that compare primary treatments in locally advanced vulvar cancer are needed.
Cisplatin and 5-fluorouracil (5-FU) have been used in the neoadjuvant setting but have not been studied extensively in recurrent vulvar cancer. However, due to a lack of effective chemotherapy agents, these drugs are often used in recurrent vulvar cancer.
Great effort has been devoted to decreasing the morbidity of surgery for vulvar carcinoma. Traditional surgery has been a large en bloc resection of the vulva with the superficial and deep inguinal nodes through a single incision with at least 2-cm margins around the tumor and deep resection to the genitourinary diaphragm (see images below). This procedure resulted in significant surgical morbidity and distressing change in body image for the patient.
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Specimen after removal with at least 1 cm margins around the tumor. (Photograph courtesy of Tom Wilson)
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The surgical defect after a radical vulvectomy specimen is removed. (Photograph courtesy of Tom Wilson)
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The surgical defect is closed after a radical vulvectomy. (Photograph courtesy of Tom Wilson)
Refinements to surgery include (1) a definition for microinvasive carcinoma that does not require radical vulvar dissection or inguinal node dissection, (2) unilateral inguinal node dissection for small ipsilateral tumors, (3) using a triple-incision technique instead of an en bloc approach, (4) using radical local resection with 1-cm margins instead of complete vulvectomy, and (5) sparing the saphenous vein in an attempt to reduce the incidence of lymphedema.[20, 21] Few high quality studies are available on the surgical treatment of early stage vulva cancer. An analysis in 2008 indicated that there was no difference in local recurrence rates between radical local excision and radical vulvectomy. Recurrence of tumor in the groin are similar between ipsilateral groin node dissection and bilateral groin node dissection in women with a well-lateralized lesion.[22]
Many gynecologic oncologists omit dissection of the deep inguinal lymph nodes, although this surgical approach is controversial. In an attempt to decrease the morbidity from inguinal node dissection, radiation alone has been used to treat the groin lymph nodes but was shown to be inferior to groin node dissection.[23] A 2009 review comparing primary groin irradiation and primary groin surgery for early stage vulvar cancer concluded there was insufficient evidence to state that radiotherapy is equivalent to surgery for vulvar cancer.[24]
Sentinel lymph node (SLN) dissection has become part of the standard of care for women with early stage vulvar cancer.{ref24, 81, 87) This idea assumes metastasis occurs first to the SLNs, followed by metastasis to the other inguinal lymph nodes. This orderly metastasis has been validated in breast cancer and cutaneous melanoma.
The results of lymphoscintigraphy and blue dye used in 59 patients with vulvar cancer was reported by de Hullu. All 37 SLNs interpreted as positive on frozen section were confirmed on final pathologic examination, resulting in a positive predictive value of 100%.[25] A more recent study examined the use of identification of the SLN in patients with squamous cell carcinoma. Patients were divided into two groups. Twenty-eight women had a vulvectomy and lymphadenectomy with identification of the SLN using lymphoscintigraphy with technetium-99 colloid albumin and 27 women had a vulvectomy and lymphadenectomy with no attempt to identify the SLN. SLN identification failed in one case. There was 1 false-negative SLN. The average number of SLNs identified was 2.2. Recurrent disease was similar in both groups. The authors did not report which patients developed recurrent disease in the inguinal area.[26]
In 2008, Ate and colleagues reported results of a multicenter observational study on sentinel node detection using radioactive tracer and blue dye in 403 patients with vulvar cancer. The results indicated that in patients with negative sentinel node(s), the groin recurrence rate is low, survival excellent, and morbidity minimal.[27]
In 2012, the Gynecologic Oncology Group published the results of lymphatic mapping and sentinel lymph node biopsy (SLNB) in 452 women with squamous cell carcinoma of the vulva.[28] Eligibility for this study included a primary tumor size of at least 2 cm but smaller than 6 cm and no clinically suspicious groin lymph nodes. All women underwent intraoperative lymphatic mapping and SLNB with isosulfan blue dye. The protocol was amended two years after study activation, requiring perioperative lymphoscintigraphy and intraoperative radiolocalization. There were 132 node-positive women, including 11 women (8.3%) with false-negative nodes. The authors believe SLNB should be offered to well-selected patients, preferably to those patients with primary tumors smaller than 4 cm, and surgery should be performed by well-trained gynecologic oncologists. If the SLNB is negative in this group of patients, the risk of groin relapse due to a false-negative SLNB is less than 3%.
A meta-analysis in 2013 examined the role of lymphatic mapping and SNLB in patients with squamous cell carcinoma. The authors reviewed 47 studies. Their conclusion was sentinel lymph node mapping for inguinal node staging using radiotracer and blue dye methods in patients without palpable inguinal nodes yielded the highest detection rate and sensitivity. False-negative results were highest in patients with midline vulvar lesions.[29]
The initial definition for microinvasive lesions was a depth of 5 mm below the basement membrane for tumors smaller than 2 cm. However, the risk of groin node metastasis in lesions with 3-5 mm of invasion was noted to possibly be as high as 20%. It was later determined that women with 1-mm invasion or less had a negligible chance of node metastasis and could be treated with wide local excision with a 1-cm clinical margin around the tumor. A GOG study suggested that women with well-differentiated tumors up to 2 mm in depth had a very low risk of lymph node metastasis.
A study by Yoder and colleagues identified three features most important in predicting tumor recurrence: depth of invasion, presence of squamous cell carcinoma at the surgical margins, and the histologic grade.[30] Omitting the groin node dissection in women with 1-2 mm of invasion can be considered if the tumor is well differentiated and the patient is elderly, debilitated, or at significant risk of lymphedema.
The risk of lymph node metastasis based on the depth of invasion
Invasion to less than or equal to 1 mm - 0% (n = 34)
Invasion to 1.1-2 mm - 10% (n = 19)
Invasion to 2.1-3 mm - 12% (n = 17)
Invasion to 3.1-5 mm - 14% (n = 7)
Invasion to deeper than 5 mm - 43% (n = 7)
In stage I lesions, 0 of 177 patients had positive findings from contralateral groin nodes when the ipsilateral node findings were negative and the lesion was not located in the midline. Therefore, contralateral groin node dissection has been omitted when patients present with a primary lesion smaller than 2 cm and have negative ipsilateral lymph node findings.
Since the early part of the 20th century, the traditional surgery has been a radical dissection of the primary lesion with a bilateral groin node dissection performed through a single incision. Although this technique was later modified to remove less skin, the primary wound breakdown rate exceeded 50%. Taussig eventually adopted a triple-incision technique in response to the high wound breakdown rate. Concern was raised over the triple-incision technique because of the possibility of residual disease in the "skin bridges" due to cancer cells in the lymphatics between the primary tumor and the lymph nodes. Hacker et al reported a series of 100 patients who had undergone surgery with a triple-incision technique and reported a 56% primary healing rate. Although 2 patients had metastasis in the skin bridge, neither of these instances were isolated metastasis.[6]
Helm et al reported findings when comparing the cases of 32 women treated with a single incision with 32 similar patients treated with a triple incision. Patients with a triple incision had a significantly shorter operative time, less blood loss, and a shorter hospital stay. No difference was observed in the overall survival or recurrence rate between the 2 groups, and none of the women in the triple-incision group developed skin bridge metastasis. The biggest difference in the 2 groups was that the single-incision group had a 19% complete wound-breakdown rate, compared to only 3% for the triple-incision group. Similar results have been noted for women with larger lesions.[31]
A less-radical approach was adopted following the discovery that the local recurrence risk was low when the pathologic margin around the primary lesion was 8 mm. When taking into account the shrinkage during tissue fixation, this translates to a 1-cm clinical margin. Deep dissection to the urogenital diaphragm is performed, but most of the vulva can be spared if the primary lesion is small.
The traditional description of a groin node dissection includes ligation of the saphenous vein during removal of the superficial groin lymphatics. A review of 139 cases of groin node dissection demonstrated that when the saphenous vein was preserved, the incidence of wound cellulitis and acute and chronic lymphedema was significantly lower. Only one patient in this series with saphenous vein preservation developed chronic lymphedema. This occurred in a patient who received postoperative radiation therapy. No evidence indicated that an attempt to save the saphenous vein significantly increased blood loss or operative time.[20]
The idea to implement radiation therapy to treat the groin lymphatics without surgery has been studied by the GOG. The GOG performed a study on the efficacy of groin irradiation compared to surgery. Women with clinically negative findings from groin nodes were randomized to radiation alone or lymphadenectomy with radiation when the groin nodes were pathologically positive. The study was discontinued prematurely as an interim analysis demonstrated a significant decrease in survival in women receiving only groin irradiation.[23]
This study has been criticized due to the radiation dosage. The prescribed dose of radiation was at 3 cm, regardless of body habitus or the actual groin node location.
Studies of CT scan data have demonstrated that this technique delivers 100% of the prescribed dose to only 18% of women, and fewer than half the women would have received more than 60% of the prescribed dose to the entire groin lymphatic area.
Many physicians now omit deep groin node dissection. Opening the femoral sheath and removing the deep nodes is not without morbidity. Deep lymph node dissection may increase the incidence of lymphedema. In addition, infection of the groin over the femoral vessels after deep groin dissection can result in catastrophic bleeding. The sartorius muscle historically was transferred to the inguinal ligament to cover the exposed femoral vessels. Judson reported this technique is not beneficial based on a randomized control trial and increased the risk of lymphocyst formation.[32]
Several authors have examined the incidence of unexpected groin failure in the presence of pathologically negative superficial lymph node findings. The incidence rate of unanticipated failure is approximately 0-5%.[33, 34, 35] These percentages match those of an older series by Stanley Way, in which he examined both nodal groups separately and found that the deep nodes (deep femoral and pelvic) were involved in only approximately 3% of cases when the superficial lymph node findings were negative. He later adopted a technique of using the deep inguinal nodes to predict the need for pelvic lymph node dissection but continued to remove both the superficial and deep inguinal nodes. A survey of a group of gynecologic oncologists found that less than 25% of respondents still perform deep inguinal node dissection.[36]
Surgery for vulvar carcinoma is often performed with the woman's legs in adjustable stirrups to facilitate both the groin node dissection and the perineal phase of the operation. A surgical team can greatly reduce operative time. After the patient is prepared and draped, make an incision approximately 2 cm below the inguinal ligament. The tissue is undermined below the Scarpa fascia. Proceed with the dissection down to the tensor fasciae latae. Next, dissect the superficial inguinal nodal group off the cribriform fascia, taking care to not injure the great saphenous vein.
If the deep nodes are to be dissected, open the cribriform fascia laterally and take this tissue as part of the specimen. Then, dissect the femoral vein free and remove the nodes from the medial portion of the femoral vein. After a deep groin node dissection, the sartorius muscle can be divided at its insertion on the anterior iliac spine and sutured to the inguinal ligament to cover the femoral vessels. Bring closed suction drains in through a separate incision and suture to the skin. Close Scarpa fascia with 3-0 absorbable sutures, and close the skin with mattress sutures or with staples.
To initiate the radical vulvectomy, outline the lesion with a marking pen and make an incision to encompass 1-cm margins around the tumor. In contrast to a simple vulvectomy, the dissection is taken down deep to the perineal membrane. Care must be taken at the posterior aspects of the incision where the pudendal vessels enter the vulva. The lower portion of the bulbocavernosus muscle should be clamped and ligated to prevent bleeding. Once the lesion is removed, the vagina and vulvar skin can be mobilized to reduce the tension on the incision. The defect is closed in layers with 2-0 polyglycolic absorbable suture, and the skin is closed with horizontal or vertical mattress sutures. The authors' preference is to use 3-0 polyglycolic acid for the mattress sutures and to reinforce the incision with a running 4-0 polyglycolic acid suture.
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The surgical defect is closed after a radical vulvectomy. (Photograph courtesy of Tom Wilson)
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Closure of a large single-incision radical vulvectomy. The complete wound breakdown rate from this procedure is often greater than 50%. (Photograph co....
Frequent sitz baths are recommended by many surgeons after surgery. Patients should dry the vulva completely after each sitz bath. A Foley catheter may be needed for a prolonged period after surgery around the urethra. Low molecular weight heparin or pneumatic compression stockings should be used in all women to prevent postoperative venous thrombosis. A Jackson-Pratt or similar type of drain should be placed in the inguinal space at the time of lymphadenectomy. Leave this drain in place until drainage is approximately 25 mL or less per day. Drainage may persist in many cases for more than 2 weeks.
A limited number of studies have been published on the impact of surgical treatment for vulvar cancer on sexual function, partner relationship, and overall quality of life.[37] Studies indicate these women, after surgery , are at high risk for sexual dysfunction, even in the absence of a functional problem after surgery. Sexual dysfunction seems to be related to a disturbance in body image, leading to hypoactive sexual disorder and aversion disorder. Depression and increasing age are risk factors for sexually active women to discontinue intercourse after surgery. Interestingly, few studies have been able to correlate sexual dysfunction with extent of surgery if the clitoris was preserved.
Women who have tumor involvement with two or more inguinal lymph nodes are likely to benefit from adjuvant radiation therapy to the inguinal and pelvic nodes. The GOG studied the use of pelvic node resection compared with radiation of the groin and pelvis. The cancer-related death rate at 6 years for women having a pelvic lymph node resection was 51% compared with 29% in women who underwent radiation. The authors concluded that radiation after vulvectomy and inguinal lymphadenectomy significantly reduces local relapses and decreases cancer-related deaths for patients with node-positive vulvar cancer.[38] More recently, Mahner and colleagues emphasize radiotherapy is the most important adjuvant treatment for women with vulvar cancer.[39] A clear benefit for radiation has not been proven in women with positive microscopic tumor in one lymph node, but, as groin recurrence is almost universally fatal, adjuvant radiation is often recommended.
Monitor patients closely after treatment for vulvar carcinoma. The most common site of recurrence is the vulva. An examination every 3-6 months for the first 2 years is recommended as more than two thirds of recurrences are in this time period. Detection of local recurrence of vulvar carcinoma is important because it can be treated by radical surgical excision. National Comprehensive Cancer Network guidelines recommend surveillance exams every 6-12 months after 2 years from diagnosis.[40]
The long-term survival rate after radical excision of a vulvar recurrence has been reported as 50-60%. Survival is better in women who originally presented with early-stage disease. Other factors that diminish the cure rate after local recurrence include disease at sites other than the vulva and a short interval from initial treatment to recurrence. For a large recurrence, an exenterative procedure can be attempted. A long-term survival rate of 38% has been reported after exenterative surgery for vulvar carcinoma.
Resection of a groin recurrence is not usually recommended. Previous radiation therapy to the inguinal area significantly impairs healing. Generally, the procedure should not be considered curative. The only situation in which resection of a groin node recurrence should be attempted is if the groin node is an isolated recurrence and the patient has not been previously irradiated.
Positive groin nodes at the time of initial surgery increase the risk of recurrence in the groin in the first 2 years. After the first 2 years, the risk of groin recurrence is low, regardless of the status of the nodes at the time of the initial surgery. There remains a long-term risk of local failure on the vulva after the surgery. A report from the Mayo clinic indicates that up to 10% of patients treated for vulvar cancer had a local recurrence more than 5 years after the original diagnosis.
Lymphocyst formation is noted in 7-19% of patients after groin lymphadenectomy. Although cellulitis after vulvectomy has been associated with an increase in the incidence of lymphedema, it has not been associated with an increase in lymphocyst formation. Do not remove drains after inguinal node dissection until the daily output of the drain is less than 25 mL.
Lymphocysts usually manifest as an asymptomatic mass in the groin. To exclude a groin recurrence, aspirate fluid from the cyst and send for cytologic evaluation. Multiple aspirations are often required and may not be curative. If the mass is symptomatic, the lymphocyst can be removed surgically. However, in one small series, lymphocysts were successfully treated by placing a drain in the groin until the output was less than 25 mL/d. The drain was then removed and a pressure dressing was placed to prevent reaccumulation of the fluid. Sclerosis of lymphocysts with Betadine solution has also been described.
Cellulitis and lymphangitis can occur after groin node dissection. The incidence rate of cellulitis requiring antibiotics ranges from 20-40%. Often, patients who develop lymphocysts are at increased risk of lymphangitis. The etiologic agent is most often a streptococcal species, and treatment with penicillin is adequate. If drains are still in place, first-generation cephalosporins may be more appropriate to treat Staphylococcus aureus.
Chronic lymphedema has been reported in 10-20% of women after groin node dissection. This can be a disabling problem and is more common if radiation is required after groin dissection. Limiting groin node dissection in women with early cancers and preserving the saphenous vein decreases the incidence of this problem. The use of graduated compression stockings after lymphadenectomy can help prevent lymphedema. If edema does develop, the use of compression stockings, massage therapy, and limb wraps can help control the accumulation of fluid. However, lymphedema can be chronic and disabling in severe cases. Many major centers offer lymphedema treatment programs.
A prophylactic quadrivalent vaccine was approved by the Food and Drug Administration (FDA) in 2006 for the prevention of anogenital lesions including genital warts, vulvar and vaginal intraepithelial neoplasia, and cervical lesions associated with HPV 6, 11, 16, and 18. The first study to demonstrate the efficacy with HPV type 16 vaccine was reported by Koutsky and colleagues in 2002.[41] This vaccine contained virus-like particles (VLPs) that do not contain viral DNA. Two studies were subsequently published examining the efficacy of the quadrivalent vaccine. These studies demonstrated significant vaccine efficacy in decreasing the incidence of anogenital lesions caused by HPV 6, 11, 16, and 18.[42, 43]
In the summer of 2008, the FDA approved marketing of the quadrivalent vaccine for the prevention of vulvar and vaginal cancer.[44] The FDA in December 2014 approved HPV 9-valent vaccine to protect against precancerous vulvar lesions and vulvar cancer.[45]
Based on work in breast cancer and melanoma, a sentinel lymph node (SLN) can be identified and can be predictive of patients who will have other involved nodes. The technique of SLN dissection is attractive in vulvar carcinoma since most women will have negative lymph nodes. If the sentinel node dissection proves to be sufficiently sensitive, full groin node dissection could be limited only to women with positive lymph nodes. There are two studies that report the efficacy of this SLN biopsy. A sentinel node can be identified in approximately 85% of women with isosulfan blue dye and 100% with the injection of Tc-99 labeled albumin.[46] The GOG lymphatic mapping and SLNB study from 2012 in 452 women supports the use of SLNB for women with primary tumors smaller than 4 cm performed by well-trained gynecologic oncologists.[28]
The combination of chemotherapy with radiation in cervical cancer has produced marked improvement in survival for locally advanced disease. This concept appears to also be effective in locally advanced vulvar carcinoma. Chemotherapy combined with radiation also may improve the cure rate in women with positive groin node findings, but acceptance of routine chemoradiation in women with positive node findings will probably require prospective evaluation.[47, 48]
A guideline update on management of vulvar cancer was released in June 2023 by the European Society of Gynaecological Oncology.[49] Brief highlights of the guideline follow.
Diagnosis and staging
In any patient with suspected vulvar cancer, diagnosis should be established by a punch/incision biopsy. Excision biopsy should be avoided for initial diagnosis, as this may hinder further treatment planning. In patients with multiple vulvar lesions, all lesions should be biopsied separately with clear documentation of mapping.
Because there is limited alignment between the American Joint Committee on Cancer (AJCC) 8th edition tumor-node-metastasis (TNM) staging and the International Federation of Gynecology and Obstetrics (FIGO) 2021 classification, and lack of evidence to base treatment on the FIGO 2021 staging, TNM classification is advised.
Treatment
For local treatment, radical local excision is recommended, with the aim to obtain histologic tumor-free margins. Extending the primary excision in a superficial fashion to include adjacent differentiated vulvar intraepithelial neoplasia is highly recommended. In multifocal invasive disease, radical excision of each lesion as a separate entity may be considered.
Postoperative radiotherapy to the vulva is indicated when invasive disease extends to the pathological excision margins of the primary tumor and further surgical excision is not feasible,
Primary chemoradiotherapy is the treatment of choice in patients with unresectable disease and should be considered for tumors that would otherwise need exenterative surgery with stoma formation.
Robert V Higgins, MD, Professor, Department of Obstetrics/Gynecology, Division of Gynecologic Oncology, Medical College of Georgia at Augusta University
Disclosure: Nothing to disclose.
Coauthor(s)
James Hall, MD, Director, Division of Gynecologic Oncology, Blumenthal Cancer Center, Carolinas Medical Center; Clinical Professor, Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill School of Medicine
Disclosure: Nothing to disclose.
R Wendel Naumann, MD, Clinical Assistant Professor of Obstetrics and Gynecology, University of North Carolina at Chapel Hill School of Medicine; Director, Minimally Invasive Surgery in Gynecologic Oncology, Associate Director, Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Carolinas Medical Center
Disclosure: Nothing to disclose.
Specialty Editors
Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Received salary from Medscape for employment. for: Medscape.
Michel E Rivlin, MD, Former Professor, Department of Obstetrics and Gynecology, University of Mississippi School of Medicine
Disclosure: Nothing to disclose.
Chief Editor
Leslie M Randall, MD, MAS, FACS, Professor and Director, Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Diane Harris Wright Professor of Gynecologic Oncology Research, Massey Cancer Center, Virginia Commonwealth University School of Medicine
van Doorn HC, Ansink A, Verhaar-Langereis MMJ, Stalpers LL. Neoadjuvant chemoradiation for advanced primary vulvar cancer (Review). The Cochrane Collaboration. 2009. 1:1-20.
Tantipalakorn C, Robertson G, Marsden DE, Gebski V, Hacker NF. Outcome and Patterns of Recurrence for International Federation of Gynecology and Obstetrics (FIGO) Stages I and II Squamous Cell Vulvar Cancer. Obstet Gynecol. April/2009. 113:895-901.
Ansink A, Stegemen M, van der Velden K, Collingwood M. Surgical interventions for early squamous cell carcinoma of the vulva (Review). The Cochran Collaboration. 2008. 3:1-20.
van der Velden K, Ansink A. Primary groin irradiation versus primary groin surgery for early vulvar cancer (Review). The Cochrane Collection. 2009. 1:1-15.
Ate GJ, Van der Zee, Oonk MH, De Hulla JA, Ansink AC, Vergote I, et al. Sentinel node dissection is safe in the treatment of early-stage vulvar cancer. J Clin Oncol. Feb 2008. 26:884-89.
[Guideline] NCCN Clinical Practice Guidelines in Oncology. Vulvar Cancer (Squamous Cell Carcinoma). NCCN.org. Available at http://www.nccn.org/professionals/physician_gls/pdf/vulvar.pdf. 01/14/16; Accessed: April 12, 2016.
FIGO Committee on Gynecologic Oncology. Revised FIGO staging for carcinoma of the vulva, cervix, and endometrium. Int J Gynecol Obst. 2009. 105:103-104.
American Joint Committee on Cancer. AJCC Cancer Staging Manual. 7th. Chicago, Illinois: Springer New York, Inc; 2010.
A large T2 carcinoma of the vulva crossing the midline and involving the clitoris. (Photograph courtesy of Tom Wilson)
A large squamous cell carcinoma of the vulva. Note the small contralateral "kissing lesion" that can be seen with vulvar carcinomas. (Photograph courtesy of James B. Hall, MD)
A large T2 carcinoma of the vulva crossing the midline and involving the clitoris. (Photograph courtesy of Tom Wilson)
Diagram of lymphatic drainage of a lateral lesion. Most lymphatics flow through the superficial inguinal nodes, deep inguinal nodes, and the node of Cloquet to the pelvic lymph node chains. Deep inguinal node findings are positive approximately 3% of the time when superficial inguinal node findings are negative. Lymphatic mapping studies indicate that 13% of cases demonstrate findings consistent with flow to the pelvis that does not involve the node of Cloquet. If the lesion is in the anterior labia minor, then contralateral flow is demonstrated in 67% of cases.
Specimen after removal with at least 1 cm margins around the tumor. (Photograph courtesy of Tom Wilson)
The surgical defect after a radical vulvectomy specimen is removed. (Photograph courtesy of Tom Wilson)
The surgical defect is closed after a radical vulvectomy. (Photograph courtesy of Tom Wilson)
The surgical defect is closed after a radical vulvectomy. (Photograph courtesy of Tom Wilson)
Closure of a large single-incision radical vulvectomy. The complete wound breakdown rate from this procedure is often greater than 50%. (Photograph courtesy of James B. Hall, MD)
Diagram of lymphatic drainage of a lateral lesion. Most lymphatics flow through the superficial inguinal nodes, deep inguinal nodes, and the node of Cloquet to the pelvic lymph node chains. Deep inguinal node findings are positive approximately 3% of the time when superficial inguinal node findings are negative. Lymphatic mapping studies indicate that 13% of cases demonstrate findings consistent with flow to the pelvis that does not involve the node of Cloquet. If the lesion is in the anterior labia minor, then contralateral flow is demonstrated in 67% of cases.
A large T2 carcinoma of the vulva crossing the midline and involving the clitoris. (Photograph courtesy of Tom Wilson)
Specimen after removal with at least 1 cm margins around the tumor. (Photograph courtesy of Tom Wilson)
The surgical defect after a radical vulvectomy specimen is removed. (Photograph courtesy of Tom Wilson)
The surgical defect is closed after a radical vulvectomy. (Photograph courtesy of Tom Wilson)
A large squamous cell carcinoma of the vulva. Note the small contralateral "kissing lesion" that can be seen with vulvar carcinomas. (Photograph courtesy of James B. Hall, MD)
A specimen from a traditional single-incision radical hysterectomy. Most radical vulvectomies are now performed through 3 incisions, with the groin nodes removed separately from the vulvectomy specimen. (Photograph courtesy of James B. Hall, MD)
Closure of a large single-incision radical vulvectomy. The complete wound breakdown rate from this procedure is often greater than 50%. (Photograph courtesy of James B. Hall, MD)
A specimen from a primary exenteration for a stage IVA vulvar cancer involving the rectum. Many of these large tumors are now treated with adjuvant chemotherapy and radiation prior to surgery, with preservation of rectal sphincter function. (Photograph courtesy of James B. Hall, MD)
TNM Categories
FIGO
Definition
Primary tumor cannot be assessed
No evidence of primary tumor
Carcinoma in situ (preinvasive carcinoma)
IA
Tumor size < 2 cm and stromal invasion ≤1 mm (a)
IB
Tumor size >2 cm or stromal invasion > 1 mm
II
Tumor of any size with extension to lower one-third of the urethra, lower one-third of the vagina, lower one-third of the anus with negative nodes
Stage III Tumor of any size with extension to upper part of adjacent perineal structures, or with any number of nonfixed, nonulcerated lymph node
Stage IIIA Tumors of any size with disease extension to upper two-thirds of the urethra, upper two-thirds of the vagina, bladder mucosa, rectal mucosa, or regional (b) lymph node metastases < 5 mm
Stage IIIB Regional (b) lymph node metastases > 5 mm
Stage IIIC Regional (b) lymph node metastases with extracapsular spread
IV
Tumor of any size fixed to bone, or fixed, ulcerated lymph node metastases, or distant metastases
IVA - Disease fixed to pelvic bone, or fixed or ulcerated regional (b) lymph node metastases
IVB - Distance metastases
(a) Depth of invasion is measured from the basement mambrane of the deepest, adjacent, dysplastic, tumor-free rete ridge (or nearest dysplastic rete peg) to the deepest point of invasion.
(b) Regional refers to inguinal and femoral lymph nodes.
Important notations and changes
1. Lymph node positivity should reflect the consensus utilized in cervical cancer staging, which is micrometastasis and macrometastasis.
2. Individual tumor cells (ITC) will not count toward lymph node metastasis.
3. This staging is to be used for all morphological types of vulvar cancer and not just the most common squamous cell carcinoma. The only exception to this is vulvar carcinoma.
4. Documentation of HPV status of the carcinoma of the vulva (HPV-associated or HPV-independent) is strongly recommended. This is assessed by p16 block-type immunoreactivity and/or positive molecular testing for HPV.
Regional lymph nodes (N)*
TNM categories
FIGO stages
Definition
NX
Regional lymph nodes cannot be assessed
N0
No regional lymph node metastasis
N1
1or 2 regional lymph nodes with the following features:
N1a
IIIA
1 lymph node metastasis each ≤5 mm
N1b
IIIA
1 lymph node metastasis ≥5 mm
N2
IIIB
Regional lymph node metastasis with the following features:
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