PMC9341270_01
PMC9341270_02
Different types of vaginal cancer and their infection rate. Various types of vaginal cancer are found in different parts of the vagina. Among them, squamous cell carcinoma, which is linked to the vaginal surface area and arises from epithelial cells, is the most prominent type of vaginal cancer. Adenocarcinoma is also found as a common type of vaginal cancer, which is responsible for 15% of all vaginal cancers. Besides, endrometriosis, testicular and some other types of cancer are noticed in the vaginal area.
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Certain cancers may spread to the vagina from their original site - such as uterine, cervical, rectal, or bladder cancers ( Figure 1 ).
Overview of vaginal cancer and stages. Vaginal cancer is a rare kind of cancer that affects the vaginal area. The cells that line the vaginal surface are the most often affected by vaginal cancer. When found early on, vulvar cancer is generally treatable. Treatment for vaginal cancer that has progressed beyond the vagina is significantly more challenging. Stage I- Only the vulva or perineum (area between the anus and vulva) have cancerous cells. Stage II- Cancer has progressed to the urethra, anus, or vaginal region. Stage III- The malignancy has progressed to the lymph nodes in the surrounding area. Stage IV- Cancer has spread to other regions of the body from the lymph nodes.
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Committee on Cancer have developed recommendations for staging and classifying vaginal cancer ( Figure 2 ). Clinical parameters are used to determine the stage of vaginal cancer.
Mechanisms of E6 and E7 overexpression due to integration of Human Papilloma Virus in Vaginal cancer. Vaginal cancer is a multi-stage process that is developed by the accumulation of DNA changes of host cell genes. Integrating HPV DNA into the host cell genome is crucial, resulting in abnormal proliferation and development. E6 and E7 genes play a crucial role in interfering with the tumor suppressor gene's function. The continued action of proteins E6 and E7 causes abnormal cell proliferation, mutation of the oncogene, and eventually vaginal cancer. The integration site is dispersed over the entire genome as chromosomally fragile areas where DNA cracks in double strands are not repaired. HPV DNA breaks are initiated when the virus is replicated, and these breaks cannot be remedied. When CDKs inhibitors (P21, P27) and P53 protein are inhibited, E6 and E7 oncoproteins damage the checkpoint of the cell cycle. DNA damaging reaction pathways regulate fusion between the two genomes by homologous or heterologous recombination. HPV genome directly binds to the host chromosome via HPVE2-BRD4 complex for dividing genomes into daughter cells.
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The oncoprotein PV-16 E7 mitigates the reaction of the DNA damage control point by boosting up the claspin proteolytic revenue during ATR/CHK1 signaling and DNA damage control point retrieval in the cell cycle at phase G2 ( Figure 3 ).