Detection of human papillomavirus type 16 DNA in consecutive genital samples does not always represent persistent infection as determined by molecular variant analysis

Persistent human papillomavirus (HPV) infection of the uterine cervix is a risk factor for progression to high-grade squamous intraepithelial lesions. Detection in consecutive genital samples of HPV-16 DNA, a frequently encou ntered HPV type, may represent persistent infection or reinfection. We unde rtook a study using PCR-single-strand conformation polymorphism (SSCP) anal ysis and sequencing of PCR products (PCR-sequencing) to determine if consec utive HPV-16-positive samples contained the same HPV-16 variant. Fifty wome n (36 human immunodeficiency virus [HIV] seropositive, 14 HN seronegative) had at least two consecutive genital specimens obtained at 6-month interval s that contained HPV-16 DNA as determined by a consensus L1 PCR assay, A to tal of 144 samples were amplified with two primer pairs for SSCP analysis o f the entire long control region. Fifteen different SSCP patterns were iden tified in our population, while 22 variants were identified by PCR-sequenci ng, The most frequent SSCP pattern was found in 75 (53%) samples from 27 (5 4%) women. The SSCP patterns obtained from consecutive specimens were ident ical for 46 (92%) of 50 women, suggesting persistent infection. Four women exhibited in consecutive specimens different HPV-16 SSCP patterns that were all confirmed by PCR-sequencing. The additional information on the nature of persistent infection provided by molecular variant analysis was useful f or 6% of women, since three of the four women who did not have identical co nsecutive specimens would have been misclassified as having persistent HPV- 16 infection on the basis of RPV typing.