Human papillomavirus (HPV) infections of the female genital tract and their associations with intraepithelial neoplasia and squamous cell carcinoma.

Human papillomaviruses (HPV) consist of a heterogenic group of viruses (32 different HPV types currently recognized) known to induce a variety of squamous cell tumors (papillomas and warts) in the skin, and on mucous membranes of respiratory, gastrointestinal, and genitourinary tracts. The most familiar HPV manifestation in the genital tract is the venereal wart (condyloma acuminatum) recognized since antiquity, and shown to be a sexually transmitted disease (STD). In 1976, two other morphologically distinct HPV lesions were described in the uterine cervix, currently known as a flat and an inverted condyloma. Subsequently, these new HPV lesions were also shown to be an STD, and in addition, they frequently seem to occur concomitantly with CIN, CIS, and occasionally with invasive cervical carcinomas as well. These morphologic findings substantiated by the recent reports on malignant transformation of HPV lesions, as well as data from animal experiments and epidemiologic surveys, have lent support to the concept that HPV might be involved in the development of cervical (and other) human squamous cell carcinomas. Further evidence has been provided by the recent discoveries of HPV structural proteins (viral antigens) and HPV type 11 DNA in lesions of CIN, and HPV 16 and 18 DNA predominantly in invasive cervical carcinomas. So far, HPV 16 and HPV 18 seem to be the only HPV types with DNA capable of existing integrated in the host cell DNA. At the moment, cervical (and other) HPV lesions are the subject of intense study utilizing epidemiologic, morphologic, immunohistochemical, biochemical, and molecular biologic methods (recombinant gene technology) to provide further evidence of the suggested causal relationship between HPV and cancer. Prospective follow-up studies are also in progress to explore the natural history of cervical HPV lesions as well as the factors (e.g., immunologic, epidemiologic synergistic actions,) modifying them. In the light of present understanding, the factors linking HPV to cervical squamous cell carcinogenesis can be summarized as follows: (1) HPV infection in the uterine cervix is a sexually transmitted disease; (2) HPV lesions in the uterine cervix seem to be equivalent to CIN in their clinical behavior, i.e., possess the potential to progress towards CIS; (3) malignant transformation seems to depend on HPV type, being conditioned by integration of HPV DNA with the host cell DNA; (4) malignant transformation most probably requires synergistic effects between the virus and chemical or physical carcinogens, or other infectious agents; (5) genetic disposition (data available on animals only) significantly contributes to the process