Human Papilloma virus (HPV)
HPV is a virus which appears in the epithelial layer and infects the squamous epithelium. About 40 sub-types of this virus infect the genitals and the transitional squamous epithelium of the skin in the columnar epithelium of the digestive and genitourinary tract. At these locations they are able to cause papillary lesions (warts). Some oncogenic sub-types of HPV (16, 18, 33 and 35) are incorporated into the DNA of the host cells and cause flat pre-malignant lesions, which may develop into squamous cell carcinomas. The best known carcinomatous lesion caused by HPV is cervical cancer. Other HPV-related cancers include penile, anal, vaginal, vulvar, mouth and cancer of the nasopharyngeal cavity. HPV virus is also implicated for lung cancer.
HPV is a frequent virus and infects about 80% of the sexually active population. The virus is usually transmitted through sexual contact. Condoms do not always protect from the infection. There is strong evidence that HPV can be spread by contaminated hands or objects. In the anus, the virus is usually transmitted by sexual contact, whereby his frequency is very high in population who prefers anal sex. The infection affects about 55% of gay men and 75-90% of HIV-positive gay men. Surveys in heterosexual men show a percentage of 12-24% of infection in the anus by HPV.
In the area of the epithelium, the virus settles in keratinocytes, especially in the cells of the basal membrane, at points where there are minor injuries. The area of transformation between squamous and columnar epithelium is unstable and vulnerable to infection. In the anus, the virus can remain inactive, especially if there is a satisfactory cellular immunity to the host. Very often, complete elimination of the virus from the area can happen. Otherwise, the virus is propagated, causing cell immortality and inhibiting the conversion of the epithelial cells of the basal membrane in keratinocytes and the apoptosis of these abnormal keratinocytes. This results in creation of papillary exophytic lesions (warts). Typical examples of this picture are the cells with large irregular perinuclear halo (koilocytes).
Some sub-types of HPV which are incorporated in the host’s cell DNA, are capable of causing increased angiogenesis and flat lesions, characterized by dysplastic cells and abnormal blood vessels. If these dysplastic cells manage to extend through the entire thickness of the epithelium, then we have a senior intra-epithelial neoplasia. Also, if they invade the basic membrane of the epithelium, then we are in front of an invasive squamous cell carcinoma of the rectum. Bowen’s disease is a form of a high-grade dysplasia in the perianal skin.
In the anal area, HPV inoculates in the perianal skin and the transformation zone of the anus. This transformation zone extends about 12 mm centrally of the dentate line and the dynamic range, where the squamous epithelium extends in the columnar epithelium of the intestinal tract. The pathologoanatomical lesions caused in the anus by HPV are distinguished in a low-grade anal intraepithelial neoplasia and a high-grade anal intraepithelial neoplasia. This classification is similar to the classification of intraepithelial neoplasms of the cervix.