HPV L1 detection discriminates cervical precancer from transient HPV infection: a prospective international multicenter study

Abstract

The benefits of cytology-based cervical cancer screening programs in reducing morbidity and mortality are well recognized. Especially, overtreatment of human papillomavirus (HPV) high-risk positive early dysplastic lesions may have a negative impact on reproductive outcomes for fertile women. To optimize the clinical management an objective standard is needed to distinguish precancer that requires treatment, from spontaneously resolving HPV infections. In the current study, we examined the prognostic relevance of HPV-L1 capsid protein analysis with Cytoactiv in an international prospective multicenter study including 908 HPV high-risk positive early dysplastic lesions (LSIL/HSIL) during a follow-up period of 54 months. The clinical end points of the study were histologically confirmed CIN3 þ as progression, CIN1/2 for stable disease and repeated negative Pap smears as spontaneous clinical remission. The difference of the clinical outcome of HPV-L1-negative and HPV-L1-positive cases was statistically highly significant (P-valueo0.0001) independent of the classification as mild dysplasia (LSIL) and moderate dysplasia (HSIL). Of the HPV-L1-negative HPV high-risk positive mild/moderate dysplasias 84% progressed to CIN3, as compared with only 20% of the HPV-L1-positive cases. The data from our study show that HPV-L1 detection allows to identify transient HPV infections and precancerous lesions within the group of HPV high-risk positive early dysplastic lesions. The high progression rate of HPV-L1-negative mild and moderate dysplasia emphasizes the precancerous nature of these lesions. A close follow-up with colposcopy and histological evaluation is advisable and removal of these lesions should be considered. The low malignant potential of HPV-L1-positive cases, however, indicates transient HPV infection, justifying a watch and wait strategy with cytological follow-up, thus preventing overtreatment especially for women in their reproductive age. Modern Pathology (2013) 26, 967-974;

Role of HPV genotyping in risk assessment among cytology diagnosis categories: analysis of 4562 cases with cytology–HPV cotesting and follow-up biopsies

“…The differences in clinical performance among the commercially available HPV assays may identify unique subsets of women with very different risk profiles, especially between assays targeting HPV L1-DNA and HPV E6/E7-mRNA. It has been documented that the HPV L1 capsid protein is significantly lower or negative in women with high-grade cervical lesions25 or disease progression 26. Conversely, HPV 16/18 E6/E7 oncoproteins were significantly higher in cervical tissue with high-grade squamous intraepithelial lesions 27.…”

HPV L1 Detection as a Prognostic Marker for Management of HPV High Risk Positive Abnormal Pap Smears

“…Using histological sections Galgano et al [17] reported for Cytoactiv a raw agreement and k of 96.9% and 0.88, respectively. With 98% raw agreement and 0.96 for kappa Mehlhorn et al [26] reported similar results for the use of Cytoactiv in cytological samples. Initial L1 studies faced the problem that the sensitivity of randomly choosen L1 antibodies was unacceptable low.…”

Establishment of epigenetic markers to predict irradiation efficacy against oropharyngeal cancer

“…We evaluated HPV infection by amplifying a portion of the L1 region of high‐risk HPV, including HPV 16, 18, 31 and 33 in the 40 training and 35 validation samples, using GP5 and GP6 primers as previously reported . Positive PCR amplification was designated as HPV‐L1(+).…”