HPV RNA Test for Cervical Cancer [Internet] (2008)

BackgroundCervical cancer is the second most common cancer in women world-wide and affects about 300 women in Norway each year. Cervical cancer develops through cellular abnormalities in the cervix that can be detected by cytological tests. With the introduction of organized cervical cytologic screening programs, the incidence of cervical cancer has been dramatically reduced. However, cytologic screening tests also have limitations, especially their limited sensitivity.Because infection with oncogenic human papillomavirus (HPV) has been identified as the underlying cause of cervical cancer, there is interest in the use of HPV testing as a screening test for cervical cancer. The overall prevalence of HPV among cervical cancers is more than 99%.We have evaluated HPV RNA testing for cervical pre cancer lesions by assessing the diagnostic accuracy of the HPV RNA tests compared with cytology and HPV DNA testing.MethodsWe have systematically searched the following databases for studies that fulfilled our criteria: Medline (Ovid) 1966 – 2007, September week 1 Embase (Ovid) 1980 – 2007 week 37 CRD databases (DARE, NHS EED, HTA) 2007, September Relevant topics and text words were combined. We also composed a search filter for diagnostic studies.NorChip AS who has developed a HPV mRNA test was invited to dispatch documentation.We included published literature based on the following criteria:Population: WomenIndex test: HPV RNA testsComparators: HPV DNA tests or cytology for screening of cervical cancerReference standard: HistologyStudy design: No limitOutcome: Test sensitivity and specificity, positive and negative predictive value or other values that describe diagnostic accuracyDevelopment of cancerTest reliabilityLanguage: English and ScandinavianWe did not include publications from conferences or abstracts.Relevance and quality was assessed according to our handbook. We used GRADE to assess the documentation for diagnostic accuracy. The results are presented in tables and in a descriptive summary. This work has been carried out by two researchers at NOKC and the report has been externally reviewed.We calculated diagnostic accuracy using 2 x 2 tables for each study.ResultsWe identified 2498 references and assessed 31 full-text articles. Five studies were included in the report and results were extracted and pooled from three of them. Details of each study are presented in evidence tables. Two of the studies were sponsored by the producers of the tests.We have assessed the quality of the documentation of diagnostic accuracy using GRADE. For HPV RNA testing, the quality is very low which means that the results are very uncertain. It is not known whether HPV RNA testing give a better diagnostic accuracy than HPV DNA testing and cytology.In summary these results showed: The HPV RNA tests had slightly lower sensitivity compared with HPV DNA tests (77 % (95 % CI 73-81) versus 92 % (95 % CI 89-94), while cytology had lowest sensitivity (61 %). The sensitivity states the probability of a positive test result if you have the disease. The HPV RNA tests had slightly higher specificity compared with HPV DNA tests (64 % (95 % CI 60-68) versus 45 % (95 % CI 41-49)), while cytology had highest specificity (81 %). The specificity states the probability of a negative test result if you are healthy. The HPV RNA tests had comparable positive predictive value with the HPV DNA tests (63 % (95 % CI 59-67) versus 57 % (95 % CI 53-60), while cytology had the highest positive predictive value (91 %). Positive predictive value states the probability of illness among people with a positive test. The HPV RNA tests had slightly lower negative predictive value compared with the HPV DNA tests (78 % (95 % CI 74-82) versus 87 % (95 % CI 83-91)), while cytology had the lowest negative predictive value (39 %). Negative predictive value states the probability of illness among people with a negative test. ConclusionsDue to spare and low quality documentation, we do not know if HPV RNA tests have a better diagnostic accuracy compared to HPV DNA tests and cytology for detection of cervical pre cancer lesions.Norwegian Knowledge Centre for the Health Services summarizes and disseminates evidence concerning the effect of treatments, methods, and interventions in health services, in addition to monitoring health service quality. Our goal is to support good decision making in order to provide patients in Norway with the best possible care. The Centre is organized under The Directorate for Health and Social Affairs, but is scientifically and professionally independent. The Centre has no authority to develop health policy or responsibility to implement policies.