HPV16-L1-specific antibody response is associated with clinical remission of high-risk HPV-positive early dysplastic lesions.

BACKGROUND/AIM: The present study was aimed at clarifying if use of a rapid human papillomavirus type 16 L1-specific antibody test could be used to improve clinical management of high-risk HPV-positive low-grade squamous intraepithelial lesion (LSIL)/high-grade squamous intraepithelial lesion (HSIL). PATIENTS AND METHODS: The study was nested within a prospective study of 801 patients with early dysplastic high-risk HPV-positive lesions to examine the prognostic significance of HPV-L1 protein detection. Serum samples of 87 patients were tested with a rapid HPV16-L1-specific antibody test. The results were correlated with the clinical outcome during 66 months of follow-up. RESULTS: A combined analysis of the 22 antibody-positive women showed that 17 were also L1 protein-positive, and 5 were L1 capsid protein-negative. An HPV-specific immune competence strongly correlates with clinical remission of low-grade squamous intraepithelial lesion (76.6%). For L1 antigen and HPV16-L1 antibody double-positive women, the risk of progression to cervical intraepithelial neoplasia grade 3 was low (5.8%). CONCLUSION: The rapid anti-HPV16-L1 test could be a promising tool to improve risk assessment and appropriate clinical management of high-risk HPV-positive early dysplastic lesions.

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

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+ 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-value<0.0001) 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.

HPV vaccine protein L1 predicts disease outcome of high-risk HPV+ early squamous dysplastic lesions.

Prediction of the clinical outcome of nonadvanced, early dysplastic lesions is one of the unresolved problems of cervical cancer screening programs. We examined the influence of human papillomavirus (HPV) L1 capsid protein detection in a randomized, prospective study of 187 high-risk HPV+ early dysplastic lesions during 36 to 46 months. The difference in the clinical outcome of the HPV L1- cases and the HPV L1+ cases was highly statistically significant (P < .0001) and independent of the classification of low-grade squamous intraepithelial lesion (mild dysplasia) and high-grade squamous intraepithelial lesion of the moderate dysplastic type. L1+ mild and moderate dysplasias, reflecting productive HPV infection, showed low malignant potential, justifying a wait-and-watch strategy to prevent overtreatment, especially in young women. L1- early dysplastic lesions, as nonproductive infections or precancerous lesions, have a high malignancy potential and close follow-up with colposcopy and histologic evaluation should be advised.

Prognostic relevance of human papillomavirus L1 capsid protein detection within mild and moderate dysplastic lesions of the cervix uteri in combination with p16 biomarker.

OBJECTIVE: To proof the prognostic relevance of HPV L1 capsid protein detection on colposcopically-guided punch biopsies in combination with p16. STUDY DESIGN: Sections of colposcopically-guided punch biopsies from 191 consecutive cases with at least 5 years of follow-up were stained with HPV L1 capsid protein antibodies (Cytoactiv screening antibody) and a monoclonal anti-p16 antibody. Fifty sections were derived from a benign group, 91 from low-grade (cervical intraepithelial neoplasia [CIN 1]) lesions and 50 from high-grade (CIN 2 and 3) lesions. RESULTS: Overall only 16.1% of the 87 L1-negative, p16-positive CIN lesions showed remission of the lesion compared to 72.4% of the double positive cases. None of the L1/p16 double negative CIN lesions progressed. CONCLUSION: HPV L1 capsid protein detection with Cytoactiv screening antibody seems to be a promising new tool to predict the behavior of HPV-associated (p16-positive) early dysplastic lesions.

Correlation of immunochemical detection of HPV L1 capsid protein in pap smears with regression of high-risk HPV positive mild/moderate dysplasia.

OBJECTIVE: To immunostain Pap smears of high-risk (hr) HPV DNA-positive early squamous lesions for detecting HPV L1 protein. STUDY DESIGN: Routinely stained archival slides from 84 mild and moderate hrHPV DNA-positive dysplasias were immunostained using a panreactive HPV L1 antibody. Follow-up smears were taken from women with remission for a mean period of 22.8 months (range, 6-46). Conization was done in patients with persistence or progression (3 and 48 patients, respectively) after a mean time of 12 months (range, 9-48). RESULTS: Twenty-nine of 84 smears (34.5%) had positively stained squamous epithelial cell nuclei. In 9 of 29 (31%) women progressive disease occurred (2 cervical intraepithelial neoplasia [CIN] 2 and 7 CIN 3 lesions on conization) 20 (69%) had remission. Of the 55 L1-negative cases, 13 (23.6%) had remission, 42 (76.4%) progressed (3 CIN 2, 38 CIN 3, 1 microinvasive carcinoma). The difference in follow-up between L1 positive and negative cases was statistically significant (chi2 test, p< or =0.001). CONCLUSION: Low and moderate dysplastic squamous lesions without immunochemically detectable HPV L1 protein are significantly more likely to progress than are L1-positive cases. Immunochemical L1 capsid detection in routine Pap smears thus offers prognostic information about early dysplastic lesions.