HPV Testing

The aetiological relationship between the high risk oncotypes of the human papillomavirus (HPV) and cervical cancer means that the presence of high risk HPV in the cervix predicts increased risk and its absence implies virtually no risk at that time. These facts mean that HPV testing could be clinically useful as a means of risk assessment either in managing borderline cytology results or in predicting risk of treatment failure, and even as a primary screening test instead of cytology. Testing for HPV has become possible on a mass scale with the advent of quality assured kit tests, such as Hybrid Capture (Digene) or Amplicor (Roche). Hybrid Capture does not involve PCR and Amplicor does include PCR. Both of these tests provide a generic positive or negative result based on a 'cocktail' of probes against the relevant high risk types detected in cervical cancer. They are very sensitive, which of course reduces their specificity and particularly in young women limits their usefulness in screening. Due to the particular importance of type 16 as well as type 18, 31, 45 and 52 for example, there is now considerable interest in typing which will add specificity to the result. An HPV-16 positive result has a higher likelihood of being associated with a high risk lesion than type 51 for example.

HPV testing is widely regarded as of proven effectiveness in triaging borderline (or ASCUS in Bethesda classification) cytology and also in follow-up after treatment for CIN. As far as screening is concerned, although HPV testing is understandably more sensitive than cytology, the results of clinical trials are required to determine how it could be used most effectively in primary screening. Currently, HPV testing is not available in the NHS Cervical Screening Programme. National pilots of HPV testing in triage have been published and concluded that HPV triage for borderline/mild dyskaryosis would be cost effective but would engender higher colposcopy rates than previously existed in the management of these lesions. With regard to follow-up, an implementation study is ongoing and should report at the end of 2006/beginning 2007. As far as HPV testing in primary screening is concerned, the results of a number of European trials will be helpful in determining exactly how best to design a HPV based programme, and whether it could replace cytology as the primary test. HPV testing is made far more feasible by liquid based cytology because it requires a liquid medium and if used in tandem with conventional cytology would require an additional sample, which in a reflex setting like triage is not convenient.

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