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.