Generally, affected women may not have any symptoms. The first sign of disease may be an abnormal Papanicolaou smear done for routine cytologic screening. Symptoms may also include abnormal vaginal discharge and irregular vaginal bleeding as part of menses, coitus or postmenopausal state. In addition, depending on the location and stage of the tumor, there may be associated pelvic pressure, pelvic pain, back pain, urinary discomfort, urinary urgency, dyschezia and bloody bowel movement.

Most vaginal cancer lesions occur at the upper third of the posterior vaginal wall. Early disease may not be readily evident on examination, especially since the blades of the bivalve speculum routinely obscure the anterior and posterior vaginal walls. However, if close inspection continues as the speculum is slowly withdrawn from the vaginal canal, then a tumor plaque, ulcer, friable lesion or mucosal nodule may be detected. More advanced lesions can present as large tumors felt on palpation that may extend to the pelvic supportive structures, pelvic side walls, urethra, urinary bladder or rectum. Diagnosis is confirmed with a biopsy of any suspicious lesions in the vaginal canal with or without the aid of colposcopy.

The cause of vaginal cancer is unknown but is thought to mirror those for the vulva and cervix such as immunosuppression, smoking, early age of coitarche, having multiple sexual partners, history of previous pelvic radiation, history of cervical cancer, or human papillomavirus infection. Vaginal dysplasia (vaginal intraepithelial neosplasia or VAIN) is thought to precede frank invasive cancer. Persistent infection of oncogenic HPV leads to the development of cervical dysplasia and invasive cancer when the dysplasia is left untreated. Although the relationship between vaginal cancer and oncogenic HPV infection is not as well described, it is generally believed that the same linear relationship holds true for the vaginal tract. Published data have described similar detection of HPV in vaginal cancer compared to vulvar and cervical cancer. History of previous pelvic malignancy also increases risk of vaginal cancer. Retrospective data from a large series of vaginal cancers show that one-third of these patients had history of previous gynecologic malignancy.

Squamous cell carcinoma (SCCA) makes up around 80% of malignant vaginal histology. The behavior of vaginal SCCA is similar to SCCA detected at other body sites. Verrucous carcinoma is a variant of SCCA that tends to be exophytic and disfiguring but has an indolent course. Adenocarcinoma accounts for 15% of primary vaginal cancer and is more likely for women with history of diethystilbestrol (DES) exposure in utero. Among sarcomas of the vagina, embryonal rhabdomyosarcoma and sarcoma botryoides are most common. As a group, sarcomas tend to be more aggressive with poorer prognosis and require multimodality therapy. Melanoma can also arise in the vagina from the mucosal melanocytes. Melanoma makes up only 3% of vaginal cancer and typically occurs in the lower third of the vagina in the anterior vaginal wall.

Vaginal cancer is staged clinically using physical examination, biopsy, x-ray radiography, cystoscopy or proctoscopy. The staging system follows guidelines established by the American Joint Committee on Cancer (AJCC) and correlates well with the International Federation of Gynecology and Obstetrics (FIGO). Vaginal cancer stages are summarized as follows.