CANCER OF THE VAGINA Dr Samar Sarsam

Cancer of the vagina is rare, representing about 1-2% of gynecological cancers. It is almost always a squamous cell cancer. The exception is an adenocarcinoma that occurs in women who were exposed to DES (diethylstilbestrol) in-utero. One of the reasons that it is rare is that cancers of the vagina that also involve the vulva are considered to be vulvar cancers; if it involves the cervix it is considered to be a cervical cancer. There is a premalignant phase for squamous cell cancer of the vagina similar to the squamous cell cancers of the vulva and cervix. The premalignant phase is vaginal intraepithelial neoplasia grade III (VaIN III). This is also sometimes called carcinoma-in-situ. The premalignant phase is usually asymptomatic but can be detected by routine Pap test. It can be treated by excision, laser evaporation or occasionally by a chemotherapy type of vaginal cream. There is no recognized cause for vaginal squamous dysplasias or cancer, although it is similar to the squamous dysplasias of the cervix.

Pathology: Squamous cell carcinoma may be ulcerative or exophytic, It usually involves the posterior wall of the upper third of the vagina, but may be multicentric. Lymphatic drainage of the vagina consists of meshwork in the mucosa and sub mucosa, the upper third drainage is as cervical cancer, the lower third as vulvar cancer, the middle third may metastasise to inguinal lymph nodes or to the deep pelvic lymph nodes. Melanoma rarely occurs in the anterior surface and lower half of the vagina. Sarcoma of the vagina occurs in children under 5 years of age, rabdomyosarcoma in the upper anterior vaginal wall called sarcoma botryoides.

Clear cell adenocarcinoma arise in conjunction with vaginal adenosis in women who were exposed to DES (diethylstilbestrol) in-utero. Adenocarcinomas of the vagina associated with DES exposure were more frequent in the 1970's and 1980's. DES, diethylstilbestrol, is a synthetic estrogen hormone that was given to pregnant women in the 1950's to try to prevent miscarriages. The female infants of these women, who took the DES, had some developmental abnormalities of their vaginas and cervices that put them at risk for developing a particular type of adenocarcinoma called a clear cell carcinoma. Metastatic adenocarcinoma to the vagina from adjacent or distant organs

Clinical findings: Vaginal cancer is often asymptomatic. May cause symptoms of abnormal bleeding, postmenopausal bleeding and foul discharge. Bleeding after intercourse is a symptom of cancer of the vagina as well as cancer of the cervix. Diagnosis of primary vaginal cancer is established after eliminating other sources of malignancies. History, examination, cytological examination of the cervix, endometrial biopsy, colposcopy and biopsy

Staging: It is clinical not surgical FIGO staging: Stage 0 carcinoma in situ, intra epithelial carcinoma I vaginal mucosa II to sub vaginal tissue but not to pelvic wall III to pelvic wall IV beyond the true pelvis or to rectum or bladder or distant metastasis

Treatment: Pre treatment evaluation, include chest x-ray, IVU, cystoscopy, sigmoidoscopy, CT-scan. Invasive squamous cell cancer of the vagina is usually treated by radiation. Although it can be removed surgically, the bladder or rectum or both would have to be removed with it in order to get a good margin around the cancer. As a general rule squamous cell cancers of the vagina do not spread early, so they are usually localized to the pelvic area on diagnosis. This is a good situation for radiation since that area can easily be irradiated and radioactive material can easily be placed into the vagina next to the cancer. The prognosis for localized disease is good.

The type of surgery and radiotherapy depend on the site of the tumor: In the upper vagina treat as ca cervix. In lower vagina as cancer of the vulva. Radiation used is external pelvic irradiation followed by intracavitary. A very small tumor may be treated by vaginectomy. Sarcoma botryoides is treated by chemotherapy plus radiotherapy. Melanomas treated with radiation and or surgery. Women who have had a hysterectomy for non cancer problems should still have a Pap test every several years. They can still develop malignant and pre-malignant vaginal changes. Prognosis: 5 year survival rate is 77% in stage I Melanomas are very malignant Sarcomas associated with recurrence

Cancer of the vulva Incidence: representing about 5% of all gynecologic cancers, and only about 1% of all female cancers in general. the incidence has been rising over the past several years. The cause for the growing number of cases is not well-understood.

Epidemiology: Predominantly a disease of older women, but occasional cases in teenagers and not infrequent in 20-40 yr old age group. Vulvar cancer is most common in women over 50 years of age, with a median age of 65 – 75 years old at diagnosis. Types 85% are squamous cell carcinoma 10% are melanoma 5% are various rarities: Adenocarcinoma: Adenocarcinomas of the vulva are also rare, but can develop from glands such as the Bartholin's glands at the vaginal opening. Verrucous carcinoma Sarcomas

Site: About 70% of vulvar cancers involve the labia (mainly the labia majora). 15% - 20% involve the clitoris, and another 15% - 20% involve the perineum, which is the area of sensitive skin located between the vagina and the anus. In about 5% of cases, the cancer is present at more than one site. Etiology Risk factors In addition to older age, vulvar cancer has been associated with a history of: infection with high-risk HPV types, (i.e.: HPV 16,18,31) multiple sexual partners/ sexually transmitted diseases cervical cancer immunodeficiency presence of chronic vaginal and vulvar irritation smoking Cancer predominantly arises in areas of vulval intra-epithelial neoplasia. HPV is thought to be the precursor.

Clinical Features & Presentation Pre-malignant lesion = Leukoplakia characterized by white patches around vulva due to skin thickening & hypertrophy it is itchy biopsy Malignancies usually present with lump (hard nodule) ulcer with sloughing base & raised edges (indurated ulcer with everted edge strongly suggests carcinoma) pain and bleeding from vulva

The size of the lesion often correlates with its progression; 50% present with lymph node involvement already present. 50% arise on one labium majus, 25% arise on a labium minus. Some cases have multiple affected areas. Young women often present with malignant change in a vulval condyloma. May have had persistent vulval itching for months or years. The classic symptom is vulvar itching (pruritus), reported in almost 90% of the women with vulvar cancer. There can also be associated pain, bleeding, vaginal discharge, and/or painful urination (dysuria). Also, women often develop a visible vulvar mass: the squamous cell subtype can look like elevated white, pink or red bumps, while vulvar melanoma characteristically presents as a colored, ulcerated growth. There can be portions of the tumor that look sore and scaly or cauliflower-like (similar to HPV-related warts)

Diagnoses thorough gynecological examination should be performed using a colposcope (special magnifying instrument) for better visualization. Any suspicious areas should be tested by applying a dilute solution of acetic acid to the region; abnormal areas typically turn white, making them easier to identify. Also, any abnormal-appearing area should be sampled along with surrounding normal tissue using a thick wedge-shaped biopsy (usually under local anesthesia). If the area is small, it should be entirely removed in the process of the biopsy (so-called excisional biopsy). Chest x-ray and CT scan of the abdomen/pelvis can be done to look for disease spread to lymph nodes and/or distant organs. If spread to bladder or rectum is suspected, endoscopy (cystoscopy and proctoscopy, respectively) should be performed

Pathology Progression of vulval intra-epithelial neoplasia (VIN) is a pre-invasive phase very like CIN and similarly associated with HPV infection - types 16, 18, 33. Even very early stages of invasion through basement membrane are associated with metastasis. This tumour spreads rapidly to inguinal lymph nodes by embolisation within lymphatic (rather than permeation). From there it passes to the femoral and pelvic nodes. Staging Unlike vaginal cancer, which is typically clinically staged, the International Federation of Gynecology and Obstetrics (FIGO) uses a surgical staging system for vulvar cancer. This means that the stage of the cancer is not actually determined until after surgery is performed and the specimen is examined by the pathologist. Like vaginal cancer, vulvar cancer has five main FIGO stages (0, I, II, III, and IV). They are:

Stage 0 - Vulvar intraepithelial neoplasia Stage I - cancer is limited to the vulva and perineum, and measures < 2 cm in size Stage II - cancer is limited to the vulva and perineum, but tumor is > 2 cm in size Stage III - cancer spread to vagina, urethra, anus, and/or the lymph nodes in the groin Stage IV - cancer spread to bladder, bowel, pelvic bone, pelvic lymph nodes, and/or other parts of the body

T N M STAGING OF VULVAR CANCERS T-0 pre-malignant change T-1A a cancer less than 2.0cm in diameter and less than 1.0mm in depth of invasion T-1B a cancer less than 2.0cm in diameter but greater than 1.0mm in invasion T-2 greater than 2.0 centimeters in diameter T-3 involves vagina, urethra or anus T-4 involves bladder, rectum or pelvic bone N-0 no lymph nodes involved N-1 lymph node metastases to one groin N-2 lymph node metastases to both groins M-0 no distant metastases M-1 any distant metastases

Vulvar cancer treatment: Treatment Basis of treatment is excision small non-invasive VIN may be treated with laser (esp. good for small multiple lesions) or modified vulvectomy NB large lesions cannot be treated with the laser as it is too painful simple vulvectomy + prophylactic post-op radiotherapy to inguinal lymph nodes for small vulval carcinomas of < 2cm radical vulvectomy if carcinoma > 2cm + lymphadenectomy (of either just inguinal or in more advanced disease inguinal, femoral and pelvic lymph nodes

Wherever possible vulvectomy is avoided because it is so traumatic and psychologically distressing and a local excision operation with 5mm borders is performed. Topical 5-fluorouracil cream is useful in 50% cases but patient tolerance is low as the cream causes ulceration. In frail elderly patients palliative care and even palliative surgery is very important as the late stages of vulval carcinoma have serious morbidity. Surgery, radiation therapy and chemotherapy are the main treatment options, and are typically used in various combinations. As with many cancers, the optimal treatment depends on the disease stage and patient factors such as age and other medical conditions.

Treatment options by stage are as follows: Wide local excision, laser surgery, or a combination of both Skinning vulvectomy Chemotherapy ointment Stage I Wide local excision Radical local excision with removal of all nearby groin/ upper thigh lymph nodes Radical vulvectomy and removal of nearby groin lymph nodes (and sometimes lymph nodes on opposite side of the body) Radiation therapy alone (in selected patients)

Stage II Radical vulvectomy and removal of groin lymph nodes on both sides of the body, plus postoperative radiation therapy to the pelvis if lymph nodes are positive for cancer Radiation therapy alone (in selected patients) Stage III Radical vulvectomy and removal of groin/ upper thigh lymph nodes on both sides of the body, plus postoperative radiation therapy to the pelvis and groin if lymph nodes are positive for cancer or if the primary vulvar tumor is very large Radiation therapy and chemotherapy, followed by radical vulvectomy and removal of lymph node removal of lymph nodes on both sides of the body. Radiation therapy (in selected patients) with or without chemotherapy.

Complications Prognosis Stage IV Pelvic exenteration, which entails radical vulvectomy and removal of the lower colon, rectum, or bladder (depending on where the cancer has spread), as well as the uterus, cervix, and vagina Radical vulvectomy followed by radiation therapy Radiation therapy followed by radical vulvectomy Radiation therapy (in selected patients) with or without chemotherapy, and possibly following surgery Complications Wound breakdown (necrosis) and infection are common problems. Chronic lymphoedema of lower limbs occurs due to node dissection in ~ 20%. Prognosis In early stage disease, when lymph nodes are not involved, the overall 5-year survival rate is 90%. Once cancer has spread to the lymph nodes, the overall 5-year survival rate drops to 50% - 70%.