Determination of the diagnostic accuracy of testing for high-risk (HR) human papillomavirus (HPV) types 16, 18 and 45 in precancerous cervical lesions: preliminary data.

AIMS: In Germany, cervical cancer screening is regulated by the German Federal Ministry of Health and Social Security and is available for all women from the age of 20 on the basis of the Papanicolaou (PAP) smear. The purpose of this study was to determine the positive predictive value of HR-HPV testing for precancerous lesions of the cervix uteri. Therefore, this study especially focused on the diagnostic accuracy of testing for one or more of the HPV types 16, 18 and 45 for all HR-HPV positive women, since HR-HPV infections with subtypes 16, 18 and 45 have demonstrated a higher risk of developing cervical cancer [Bulk S, et al. Br J Cancer 2006; 94:171-5].

METHODS: Between 2007 and 2008 a total of 586 women were recruited: a group of 477 women with a history of known cervical lesions and/or HPV infections (eligibility criterion: HR-HPV DNA positive test result with HC2T) and a group of 109 women who were examined as part of their routine cervical cancer screening. Baseline HR-HPV status was measured at enrollment with the FDA-approved Hybrid Capture(R) 2 HPV DNA Test and the HR-HPV 16/18/45 Probe Set Test (HC2T, PST; QIAGEN, Hilden, Germany). Both tests use hybrid capture hybridization genotyping technology. Cervical smears were classified according to the Second Munich Nomenclature (1989). The results were converted to the nearest equivalent in the Bethesda system. In general, study subjects were followed up semiannually for a period of 1(1/2) years. The histopathological endpoint of CIN 2-3 lesion was used as a surrogate endpoint.

RESULTS: Preliminary data for 194 women of the risk group (43.5%) and for the complete control group were available. To date, CIN 2-3 was confirmed in 77 HR-HPV DNA positive women. 85.7% of these lesions were positive for one or more of the HR-HPV types 16, 18 and 45 (PST+). 88.2% (60/68) of the histologically confirmed CIN 3 lesions and six out of nine (66.6%) CIN 2 lesions were positive PST+. Furthermore, all women with a histologically confirmed squamous cell carcinoma (n = 4) were PST+. Besides, three (50%) out of six detected CIN 1 lesions were PST+. Nonetheless, histology confirmed no malignancy in three cases. Two of them were PST+.

CONCLUSION: These preliminary results demonstrate that starting cervical cancer screening at the age of 20 years remains important as seventeen (25%) of the 68 histologically verified CIN 3 lesions arose in women who were younger than 30 years. Furthermore, our data suggest that adding an HR-HPV test that detects one or more of the HR-HPV types 16, 18 and 45 in conjunction with cytology could help to identify women with an underlying cervical lesion who have an elevated risk of developing severe cervical lesions. This might offer the opportunity of a decrease in incidence and mortality rates that are related with invasive cervical cancer.