Integration of human papillomavirus (HPV) DNA into the host cell genome is a frequent event in cervical carcinogenesis, even though this phenomenon does not seem to be mandatory for cervical cancer development. Our objective was to describe the load and physical state of HPV type 16 (HPV16) DNA in a series of cervical samples representative of the natural history of cervical cancer. We used a combination of three real-time PCR assays targeting E6, E2, and albumin genes to calculate HPV16 load (E6 and albumin) and the E2/E6 ratio as a surrogate of integration. This method was applied to 173 HPV16-positive cervical samples. Results show that viral load increases with the lesion grade (from 102 HPV16 DNA copies per 10 3 cells in normal samples up to 56,354 copies per 10 3 cells in cancers), while E2/E6 ratio decreases (from 1 in normal samples down to 0.36 in cancers). We propose that, according to this technique, an HPV16 viral load of higher than 22,000 copies/10 3 cells or an E2/E6 ratio of lower than 0.50 allows the identification of women with prevalent high-grade lesions or worse with a high specificity. In conclusion, both viral load and E2/E6 ratio, used in combination with an appropriate cutoff value, are suitable to screen women with prevalent cervical intraepithelial neoplasia grade 2 or 3 or cancer. Therefore, these assays would be useful in addition to routine HPV testing to more accurately identify women with (pre)cancerous lesions.

No abstract

No abstract

High grade cervical intraepithelial neoplasia (CIN 2/3) have a high potential to progress to invasive cervical cancer (ICC). Pap testing including follow-up and treatment of CIN 2/3 is currently the best prevention of ICC, but is associated with morbidity, namely obstetrical adverse effects and psychological distress. Human papillomavirus (HPV) is universally accepted as the necessary cause of ICC. The objective of the present study was to describe the type-specific prevalence of HPV in CIN 2/3 in France and hereby to locally estimate the potential benefit of an HPV 16/ 18 L1 virus-like particles (VLP) vaccine. A total of 493 formalinfixed and paraffin-embedded CIN 2/3 specimens were analyzed. Medical records were examined for patient related data. HPV were genotyped with the INNO-LiPA assay allowing the detection of 24 HPV genotypes. The overall prevalence of LiPA detectable HPV was 98%. The most prevalent genotype was HPV 16 (62%) followed by HPV 31 (15%), 33 (12%), 52 (9%), 51 (8%), 58 (7%), 35 and 18 (4%). Multiple infection with at least two different highrisk (HR) HPV genotypes was observed in 26% of all specimens including 2.6% with HPV 16 and 18 multiple infections. The present study indicates that HPV 16 is by far the most common HPV type associated with CIN 2/3 in France. With an HPV 16 and 18 prevalence of 64%, HPV 16/18 L1 VLP vaccines would be expected to significantly reduce the burden associated with the management and treatment of CIN 2/3 in France. ' 2007 Wiley-Liss, Inc.

No abstract