Prognostic Marker for HR HPV Associated Early Squamous Lesions: HPV L1 Capsid Protein Detection by Immunochemistry

Objective: The effectivness of screening programs has considerably reduced the incidence of invasive cervical cancer. Intraepithelial precursor lesions are frequently detected and, as a result, their treatment-related costs soared. Until today no morphological criteria or molecular markers exist to identify those precursor lesions that will not regress but progress to cancer, hence selecting for those women who benefit from costly surgical procedures. In a previous retrospective study we showed that HPV high risk associated mild and moderate dysplastic lesions without immunochemical detectable HPV L1 capsid protein on routine Pap smears are significantly more likely to progress (80%) than are L1 positive cases (20%). The aim of our new study was to validate these findings in a prospective study of HPV high risk associated early sqamous lesions.

Study design: Routinely stained Pap smears of 211 women showing early (mild and moderate) dysplastic lesions dysplasia were imunochemically stained with a panreactiv HPV L1- specific monoclonal antibody (Cytoactiv®). HPV high risk infection was determined in all the lesions by the Hybrid capture 2-test (HC2®). Follow up smears were taken in intervals of 3 to 6 month. Conisation was performed if clinically indicated.

Results: 119 of the 211 HPV high risk associated early dysplastic lesion were L1- negative and 92 cases L1-positive, so far with a profoundly different outcome between the two groups. A remission of the lesion was found in only 4 L1-negative but 40 L1-positive cases. Histology confirmed 7 CIN 1, 10 CIN 2 and 68 CIN 2+ lesions (2 invasive carcinomas, 18 CIS, 38 severe dysplasias, 10 CIN 2–3) in the L1-negative group, but 1 CIN1, 4 CIN 2 and 11 CIN 2+ cases (1 CIS, 6 severe dysplasias, 4 CIN 2–3) in the L1-positive group. The remaining L1-negative and positive cases cytologically persisted as early dysplastic lesions so far.

Conclusion: The prospective study data confirm the prognostic relevance of HPV L1 capsid protein detection for early dysplastic lesions. Immunocytochemical HPV L1 staining therefore is a useful tool for the triage of HPV high risk associated early dysplastic lesions separating patients carrying a lesion with a high progressive capacity from those with dysplasias which are more likely to regress.