Histological correlates of clinically occult human papillomavirus infection of the uterine cervix

Occult infection of the uterine cervix by human papillomavirus (HPV) is assumed when viral DNA sequences are detected from cervical swabs but no lesion is detectable and the Papanicolaou smear is negative. In an attempt to identify what histological changes correlate with occult infections, DNA was extracted from 200 cervical swabs taken from hysterectomy specimens. The DNA was analyzed by Southern blot hybridization for the presence of HPV sequences. Eleven cases (5.5%) were positive. The entire cervix from each case as well as from 28 negative cases was processed for histological analysis. One of the positive cases contained a CIN 2 lesion. The other 10 showed parakeratosis, papillomatosis, acanthosis, as well as focal nuclear pleomorphism and perinuclear halos (borderline koilocytotic atypia) in proportions equal to the negative controls. In situ hybridization analysis of the cases that showed borderline koilocytotic atypia were negative. These findings confirm that clinically and cytologically occult HPV infection of the uterine cervix is not associated with diagnostic histological changes. This underscores the need for caution when interpreting cervical biopsies that show changes suggestive, but not absolutely diagnostic, of HPV infection. Further, the precise epithelial location of the virus remains unclear.