Assessment of precancerous lesions of the uterine cervix for evidence of human papillomavirus infection: a histological and immunohistochemical study.

Cervical biopsies obtained by colposcopic direction from 358 women were histologically examined for squamous dysplasia (cervical intra-epithelial neoplasia; CIN) and human papillomavirus (HPV) infection. Of the 358 biopsies, 136 were stained by an immunoperoxidase method using an antiserum against genus-specific (common) antigen of bovine papillomavirus. HPV antigens were detected in 40% of biopsies showing definite histological evidence of HPV effect, and in 7.9% and 2.6% of those with possible or no HPV effect, respectively. HPV effect was commonly seen in association with CIN. The frequency of histological evidence of HPV effect and positive immunoperoxidase staining decreased with increasing grades of CIN. HPV antigen was found in 57% of areas of HPV change with minor atypia, 34% of zones of CIN I and in only 8% of zones of CIN II. No antigenic staining or definite histological evidence of HPV effect was observed within areas of CIN III. Antigen was generally confined to the nuclei of superficial koilocytes, cells with lesser degrees of perinuclear clearing and parakeratotic cells. These results how a strong association between HPV infection and precancerous lesions of the uterine cervix and are consistent with the hypothesis that production of the HPV structural antigen requires a high degree of squamous cell maturation. The immunoperoxidase findings and the histopathological observations support the view that HPV change and dysplasia are part of a morphological continuum in which the cytopathic effect of HPV is expressed mainly in lower grades of dysplasia.