Human papillomavirus testing and its application in cervical cancer prevention

Sammanfattning: SUMMARY Because of the strong causal relationship between persistent infections of human papillomavirus (HPV) and cervical intraepithelial neoplasia (CIN) and cancer, HPVtesting has been proposed for improvement of cervical screening programs, including triaging and follow-up after treatment for CIN. We developed two new methods for HPV-testing with genotyping: A high-throughput HPV genotyping method that uses mass spectrometry for detection of the products of type-specific mass extend reactions, and a method with particularly sensitive detection of a broad spectrum of HPV-types, also in the case of multiple infections, that uses type-specific probes coupled to fluorescent beads for detection on the Luminex platform. The utility of HPV-testing was evaluated in 3 different studies: A general primer PCR-based genotyping method and the commercial Hybrid Capture (HCII) assay were compared for sensitivity and specificity for detection of CIN in secondary screening and in follow-up after treatment for cervical dysplasia. The sensitivities were high for both methods, although somewhat higher for the PCR method, but the concordance between the methods was substantial. The performance of HPV-genotyping for prediction of recurrence after treatment for CIN was compared to that of cytology. Only HPV-genotyping could predict all cases of CIN grade II or worse in histopathology, and all cases of CIN I or worse in cytology during follow-up had persistence of HPV. The applicability of HPV-genotyping was also evaluated in a secondary screening setting. Different high-risk HPV types had substantial differences in risk for presence of CIN III or worse among women with ASCUS and CIN I in cytology, suggesting that HPV typing could be useful for further optimization of ASCUS/CIN I triaging strategies. In summary, 2 HPV-genotyping methods with different applicability have been developed and validated. We also conclude that HPV genotyping is useful both in secondary screening as well as in follow-up after treatment for CIN.