Vaginal cancer commonly occurs among women between the ages of 50-70 affecting about 1 of every 1,100 women. Most vaginal cancer develops in the squamous cells which are the thin layer lining the vaginal wall. Cancer that has developed in the vagina is known as primary vaginal cancer and when it has developed in some other part of the body but has spread to the vagina, it is known as secondary cancer. Some of the risk factors of developing vaginal cancer include lower genital tract neoplasia, immunosuppression and smoking. The exposure to diethylstilbestrol in utero has also illustrated high risk for women particularly in terms of cancer of the vagina and the cervix. There are several types of vaginal cancer; squamous cell carcinoma, adenocarcinoma, melanoma and sarcoma. Around 70 out of 100 cases of vaginal cancer are squamous cell carcinoma which develops slowly starting as pre-cancerous changes into a cancerous disease. Adenocarcinoma generally affects women over the age of 50 and around 9 out of 100 cases of vaginal cancers are melanoma which develops from pigment-producing cells. Sarcoma is cancer that develops in the cells of bones, muscles and connective tissues, forming deep in the wall of the vagina and around 4 out of 100 cases of vaginal cancer are considered sarcomas.

Precancerous Lesions in the Vagina

Vaginal intraepithelial neoplasia (VaIN) is the development of abnormal cells in the vagina with the potential to become cancer in some cases. It is often detected with the cervical dysplasia, known as cervical intraepithelial neoplasia (CIN) which is the precancerous lesions of the cervix. In several cases, the precancerous lesions are attributed to HPV. The treatment options for some of the precancerous lesions include estrogen hormone therapy and laser surgery. The management of these lesions can help curb the development of some of the common types of vaginal cancer.

Association of HPV and Vaginal Cancer

Globally, it is estimated that around one-third of infection-associated cancers develop because of HPVs. There are various types of Human papilloma virus (HPV) that can cause warts in different parts of the body including the female genital area. These genital warts are known as condyloma acuminatum which may produce no signs until the pre-cancerous or cancerous changes develops. The high-risk types of HPV include HPV 16 and HPV 18 which can produce various proteins interfering with the normal functioning of the tumor suppressor gene products. HPV is contagious and can be passed on to others during skin-to-skin contact or through sexual activity. As HPV disease remains common, it is important to develop immune therapies for diseases caused by HPV. In the lifetime of an individual, the risk of developing an HPV infection at least once with the oncogenic HPV type is believed at be around 80%. Therefore, the American Cancer Society recommends that women aged between 30 – 65 have both a Pap test along with an HPV test every 5 years.

Preventive measures with Pap tests and HPV vaccines

As HPV infection is considered one of the major risk factors, vaccination to protect against HPV infection is important. The vaccine can protect against the high-risk subtypes such as 16 and 18 while some vaccines can also offer protection against subtypes that cause genital warts. The American Cancer Society recommends that routine HPV vaccine for children should be initiated at the age of 11 or 12 although it could even be started as early as age 9. However, in an effort to prevent the development of vaginal cancer, it is essential to identify the risk factors and to treat any of the pre-cancerous vaginal changes. Therefore, Pap tests and pelvic examination are important to detect the vaginal intraepithelial neoplasia. As cervical cancers are more common than vaginal cancer, Pap smear test involves taking samples from the cervix although some cells of the vaginal wall may also be collected at the same time. However, one of the priorities of the Pap test is to determine the presence of pre-cancers and early cervical cancers and not vaginal cancer.

Diethylstilbestrol (DES) and Association with Vaginal Cancer

DES is a synthetic form of estrogen which was administered to women between 1940 and 1971 to prevent premature labor, miscarriage and other complications of pregnancy. Research in 1971 shows this endocrine-disrupting chemical can cause cancer of the vagina and the cervix called clear cell adenocarcinoma and therefore the physicians ceased to administer it soon after. The daughters of women who were exposed to DES – called DES daughters – are at 40 times the risk of developing clear cell adenocarcinoma of the lower genital tract. As these women are at increased risk of developing abnormal cells of the cervix and vagina, it is recommended that they have an annual Pap test and pelvic examination.

Oncogenes and Tumor Suppressor Genes

There are two types of genes called oncogenes and tumor suppressor genes that play a critical role in the development of the disease. Normally, the proto-oncogenes are responsible for the normal growth of cells and when the proto-oncogenes mutate, it becomes ‘activated’ meaning the cells can grow out of control thus resulting in cancer. Most of these mutations are not inherited but are acquired. The oncogenes are activated by chromosome rearrangements or with gene duplication. The tumor suppressor genes are responsible for slowing down the cell division and are involved in the process known as programmed cell death (apoptosis). When any mutation in this gene occurs, the cells can also proliferate in an uncontrolled manner resulting in cancer.

A Novel Approach for the Treatment of Small-Cell Neuroendocrine of the Vagina

Primary vaginal small-cell neuroendocrine carcinoma is considered extremely rare and despite multimodal therapy, the disease presents poor prognosis with around 85% of the affected individuals die within a year of diagnosis. A case study had shown a patient diagnosed with primary vaginal small-cell neuroendocrine carcinoma had started treatment on chemoradiation based on the results of gene expression of tumor tissue and had a 14 months progression-free survival (PFS). This illustrates that there could be a benefit by including molecular profile suggested regimen to a multimodal therapeutic approach for recurrent vaginal small-cell neuroendocrine cancer.