Vaginal cancer is defined as a lesion originating from a vaginal cancer. It is rare and accounts for only 2% of malignant tumors of the female genital tract. However, the vagina is a common site of metastasis for malignant tumors of the female reproductive system. Tumors of the cervix and vulva can directly invade the vagina, while endometrial cancer and trophoblastic disease can metastasize to the vagina via lymphatic or vascular routes. Other systemic malignancies may also invade and metastasize directly to the vagina, such as tumors of the bladder, urethra, adrenal glands, and rectum, and tumors of the breast, lung, or other sites. If the lesion invades the cervix and involves the ectocervix, it is classified as cervical cancer; if the lesion is confined to the urethra, it is diagnosed as urethral cancer; if the lesion involves the vulva, it is diagnosed as vulvar cancer. Most vaginal cancers occur in menopausal or older women. Younger patients are associated with cervical intraepithelial neoplasia and human papillomavirus (HPV) infection. Nearly 90% of primary vaginal cancers are squamous cell carcinomas and adenocarcinomas are rare. Up to 30% of patients with primary vaginal cancer have a history of cervical carcinoma in situ or invasive carcinoma 5 years earlier. Some vaginal cancers develop from vaginal intraepithelial neoplasia (VAIN) and may also be triggered by previous pelvic radiation therapy. 1. Screening Patients with total hysterectomy for benign disease are at very low risk for vaginal cancer and therefore routine screening for vaginal cancer is not recommended in this population. Patients with a history of cervical intraepithelial neoplasia or invasive carcinoma have an increased risk of vaginal cancer, but routine cytologic screening has a low detection rate; combined use of HPV testing may extend the screening interval and improve cost-effectiveness. 2.Staging Primary vaginal cancer staging. 3.Vaginal intraepithelial neoplasia Patients with abnormal Pap smear and lesions not visible to the naked eye need colposcopy and Lugol iodine test. If an abnormal site is found under colposcopy, a biopsy (usually performed under anesthesia) is required. If the lesion involves the vaginal fornix, an excisional biopsy is required, and up to 28% of VAINs are found to have occult cancer there. Treatment of VAIN must be individualized. There are many treatment options, including local surgical excision or ablation, and endovenous radiotherapy. Choosing the right option requires careful consideration of several factors, including the patient’s general condition, type of pathology, location and extent of the lesion, and the skill level of the provider; it is also important to protect the adjacent ureter, bladder, and rectum, which can lead to fistula formation if damaged or compromised. Those who have received prior pelvic radiotherapy are at higher risk of fistula. Carbon dioxide laser vaporization, is an effective treatment for VAIN. It is usually performed under local or general anesthesia. Topical application of fluorouracil (5-FU) is indicated for large lesions or multiple lesions. The method is relatively simple and can be performed on an outpatient basis without anesthesia or complex instruments. Adverse effects are usually mild as long as they do not exceed 2 times in 1 week. Imiquimod (5%) cream can be used as an alternative in younger, HPV-positive patients with multiple lesions and high-grade lesions (VAIN grade 2 and 3). Excision of lesions by loop electrodebrider or cold knife is particularly indicated for lesions in the fornix. If the lesion is extensive and nearly involves the whole length of the vagina, total vaginal excision and thick flap grafting are required when other conservative treatments are ineffective. 4.Infiltrating carcinoma Most patients present with painless vaginal bleeding and drainage and can be diagnosed clearly by biopsy of the lesion visible to the naked eye using speculum examination. Biopsy can be performed on an outpatient basis and under anesthesia if necessary. The treatment of vaginal cancer should follow the principle of individualization, and the treatment plan should be determined according to the stage of the disease and the location of the lesion. Despite tumor erosion and various treatments that may lead to vaginal narrowing or shortening (especially in older women), vaginal function should be preserved as much as possible. (1) Surgery: Because of the proximity of the vagina to the bladder and rectum, surgical treatment of vaginal cancer is limited. In stage I patients with lesions involving the upper posterior vaginal wall, extensive hysterectomy, superior vaginal resection (at least 1 cm of lesion next to the incision margin) and pelvic lymph node dissection are possible if the uterus has not been removed. If the hysterectomy has been performed, radical supravaginal resection and pelvic lymph node dissection are performed. (ii) Ovarian transposition (abdominal or laparoscopic) prior to radiotherapy in young patients selected for radiotherapy, or surgical staging of enlarged positive lymph nodes in selected patients. (iii) Pelvic organ contouring in stage IVA patients, especially if combined with rectovaginal fistula or vesicovaginal fistula, and in some patients may also require removal of pelvic lymph nodes or preoperative radiotherapy. If the lesion involves the lower third of the vagina, bilateral inguinal lymph nodes should be considered for resection. (4) Patients with central recurrence after radiotherapy undergo pelvic organ contouring. (2) Radiotherapy: Most patients with vaginal cancer require radiotherapy, usually combined with external irradiation and brachytherapy (intracavitary postmortem or intertissue insertion). The plan of radiotherapy needs to be adjusted according to the location of the tumor and the relationship between the tumor and the surrounding vital tissues, and the external radiation and brachytherapy may vary considerably from plan to plan. Small focal stage I (or even stage II) may receive brachytherapy alone, and combined external irradiation may reduce the risk of local-regional recurrence. Larger lesions are treated with approximately 45-50 Gy of external radiation to reduce tumor size and treat pelvic lymph nodes, followed by supplemental brachytherapy or external radiation for primary lesions visible to the naked eye and involved lymph nodes. Local control can be improved when the primary lesion receives a dose of more than 70 Gy. To achieve the required treatment volume for the whole tumor without exceeding the tolerance of surrounding normal tissues, brachytherapy is the simplest and easiest method. Brachytherapy is preferred whenever possible, but for some patients with large lesions and lesions adjacent to important tissues (e.g. rectovaginal septum), the use of highly conformal external radiation supplementation can provide uniform coverage of the entire tumor with the radiation dose. If the lesion involves the lower third of the vagina, the inguinal lymph nodes should be treated. The use of concurrent radiotherapy for vaginal cancer has been reported to be limited. A recent study based on US national cancer data and including 13,689 patients with vaginal cancer showed that concurrent radiotherapy increased from 20.8% to 59.1% from 1998 to 2011, that median survival was longer in patients treated with concurrent radiotherapy than in patients treated with radiotherapy alone (56.2 months vs. 41.2 months), and that concurrent radiotherapy was an independent prognostic factor for prolonged survival. independent prognostic factor for prolonged survival. (3) Prognosis: Previous data showed that the overall 5-year survival rate for vaginal cancer was only about 52%; however, recent data from a large medical center suggest that the 5-year survival rate for vaginal cancer is close to that of cervical cancer. cases). 5. Rare pathologic types of vaginal malignancies (1) Adenocarcinoma: Vaginal adenocarcinoma accounts for approximately 10% of primary vaginal cancers and may originate from vaginal adenopathy due to diethylstilbestrol (DES) exposure, from residual mesonephric tissue, paraurethral glands, or endometriosis lesions. DES-associated clear cell carcinoma of the vagina occurs in younger women, but now that DES-exposed individuals are over half a century old, DES-associated tumors are now rare. a 2007 study at the M.D. Anderson Cancer Center that included 26 patients showed that the mean age of onset of non-DES-associated adenocarcinoma of the vagina was 54 years. Treatment of adenocarcinoma is similar to that of squamous carcinoma. However, adenocarcinoma has a higher risk of local or distant recurrence, and even if the lesion is small, comprehensive treatment should be emphasized. Vaginal DES-associated clear cell carcinoma usually has a good prognosis with an overall survival rate of 78%. The prognosis of non-DES-associated adenocarcinoma of the vagina is significantly worse than that of squamous carcinoma. In 26 patients in the M.D. Anderson Cancer Center study, the 5-year overall survival rate was only 34%, and the rates of local recurrence and distant metastasis were both high. (2) Vaginal malignant melanoma: Vaginal malignant melanoma is quite rare, with almost all cases occurring in white women (Chinese vaginal malignant melanoma also develops – author’s note). The lesions are usually located in the lower part of the vagina, especially in the anterior vaginal wall. The majority of vaginal malignant melanomas are deep invasive carcinomas, and the primary treatment is radical surgery, usually combined with pelvic organ contouring. Recent reports suggest that more conservative local excision (usually combined with postoperative radiotherapy) has survival rates equivalent to radical surgery. The overall 5-year survival rate for this disease is approximately 15%. (3) Vaginal chylosarcoma: Vaginal chylosarcoma is a highly malignant form of rhabdomyosarcoma. It occurs in infants and children and presents with vaginal drainage, bleeding, or a swelling at the vaginal opening. The treatment in the past was pelvic organ contouring, but the survival rate was extremely low. Recently, the use of conservative surgery combined with preoperative or postoperative radiotherapy has significantly improved survival rates. The majority of chemotherapy regimens are VAC regimens (vincristine, actinomycin D and cyclophosphamide). Surgery is preferred if the lesion is small and can be resected and the organ preserved. If the lesion is large, chemotherapy or external radiation radiotherapy or brachytherapy may be given preoperatively. Expanded field radiotherapy is not recommended because it can disrupt or interfere with the ossification center and lead to impaired pelvic development in pediatric cases.