HPV L1 capsid protein detection in high-risk human papillomavirus-positive cervical smears

Abstract Background: The L1 capsid protein is a viral nuclear protein that encapsidates the human papillomavirus (HPV) DNA to build new infectious particles. Previous studies in immune-competent patients have shown that detectable L1 protein in lowgrade squamous intraepithelial lesion (LSIL) smears is associated with remission in 60–75% of cases. Thus, the test can reduce interventions by approximately 75%. Objective: This study was performed to evaluate the use of HPV L1 capsid protein detection on cytology samples in a population with relatively high human immunodeficiency virus (HIV) prevalence and with known high-risk HPV (hrHPV) DNA results. Setting: Samples were obtained during a cervical cancer screening study at primary healthcare clinics in the Tshwane district, Gauteng. The HIV prevalence of the target group was estimated to be between 20% and 30%. Method: Conventional cervical cytology smears of 575 women were microscopically assessed and diagnosed. In addition, women were tested for the presence of HPV DNA on a cervical or vaginal sample. Immunocytochemical analysis was performed on morphologically abnormal smears and on a 52 control group smears reported to be negative for HPV DNA and morphological abnormalities. The detection of L1 capsid protein was carried out with the Cytoactiv® HPV L1 screening set, an antibody-based immunocytochemical stain. Results: A cytological diagnosis of LSIL was made in 19 women (3.3%), high-grade squamous intraepithelial lesions (HSILs) in 42 (7.5%) and malignancy in 1 (0.2%). Of the LSIL cases, 10 of 19 (52.6%) stained positive for the presence of the L1 protein, while only one of 42 HSIL (2.4%) cases stained positive. Three hundred and four cases (52.9%) tested positive for hrHPV DNA, including women with LSIL, HSIL and malignancy. All of the control cases stained negative for the L1 capsid protein. Conclusion: hrHPV was not a useful triage test for women with abnormal cellular morphology in this population. Promising results were reported for Cytoactiv® immunostaining as a triage test for patients with LSIL, but it added no value to samples known to be HPV-negative or reported to be morphologically negative. The immunostaining of smears reported to be HSIL or worse were almost universally negative, supporting the diagnostic accuracy of cytology and the expectation of persistence or progression of these lesions.