Human Papilloma Virus

Condyloma acuminatum: is a benign squamous papillomatous lesion (wart-like, verrucous lesion) that commonly occurs on or around the external genitalia (vulva, perineum and vagina) but also on the cervix (rarely).

The lesions are sexually transmitted and induced by HPV, mostly types 6 and 11.

Cervical cancer: intraepithelial and invasive squamous cell neoplasia is one of the most common tumours in women.

Epidemiology of increased risk for cervical cancer and precancerous dysplasia is:

• Early age at first intercourse

• Multiple sex partners

• High risk male sex partners

Rarity in virgins and nuns suggests sexual transmission of an oncogenic agent from male to female at an early age.

In fact risk factors for cervical cancer can be related to the likelihood of acquiring HPV infection; some studies show that 99.7% (!) of cervical carcinomas are due to HPV.

Altogether ~22 different types of HPV (out of a total of ~70) have been found to infect the ano-genital tract and most of these can be related to abnormalities of squamous epithelium:

• Squamous cell cancers of the uterine cervix contain HPV types 16 or 18 in >90% of cases. These viruses are also contained in presumed precursors (e.g. carcinoma in situ) of invasive cancer.

• Genital warts with low malignant potential are caused by distinct HPV types (low-risk types e.g. HPV-6 and HPV-11)

HPV in low risk conditions is free in the cytoplasm of the cell (episomal) whereas in high-risk lesions or in invasive cancer the virus is incorporated or integrated into the nuclear genomic DNA of the host cell.

In high-risk types (HPV-16 or 18), part of the HPV genome (E6 and E7 genes) can be shown to have the ability to transform or ‘immortalise’ cells in tissue culture:

• E6 protein has an affinity for p53 tumour-suppressor gene and speeds its breakdown

• E7 protein binds to the retinoblastoma (Rb) gene product and inhibits its function

Thus HPV is an important factor in the causation of cervical precancerous and cancerous lesions. Co-factors include other viruses (e.g. herpes), bacteria, tobacco, cigarette smoking, use of oral contraceptives and other environmental agents or host factors. However not every person who is infected with HPV will develop an epithelial abnormality or cancer.

Category: Microbiology Notes