Clinical Significance Of HPV L1Capsid Protein Detection In Cervical Exfoliated Cells In High-risk HPV Positive Women

Background:Cervical cancer ranks as the third most common malignancy in women worldwide, about528,000new cases and266,000deaths are estimated to have occurred every year, with85%of the cases and deaths occur in the economically developing world. Persistent infection of high-risk Human Papillomavirus (HR-HPV) is a causal factor for cervical cancer and precancerous lesion tissues. EUROGIN (European Research Organization on Genital Infection and Neoplasia) roadmap has recommended HPV testing as primary screening for cervical cancer in2011. The United States food and drug administration (FDA) has approved HPV testing as primary screening for cervical cancer in2014. Accumulated evidence shows that HPV testing offers a higher sensitivity, repeatability and reliability but a lower specificity than cytology while identifying high-grade cervical intraepithelial neoplasia (CIN). Thus, HPV testing alone may result in increased excessive diagnosis and treatment, and a proper triage is indispensable for HPV-positive populations. The cervical cytology and HPV16/18type detection are mainly recommend methods for high risk HPV positive women, cytology triage needs well trained cytologists, who are underrepresented in less developed countries including China. The promotion and application of HPV16/18detection will be limited because of the lack of qualified PCR lab in grassroots medical units.HPV L1capsid protein is the major structural protein of HPV infection early, it is the best characterized in terms of eliciting an immune response by generation of HPV type-specific antibodies. HPV L1capsid protein can reveal the status of productive and active HPV infection in cervical cells. Current study found that the expression rate of HPV L1capsid protein in high-grade CIN (CIN2+) is lower than that in low-grade CIN (CIN1). Furthermore, the absence of HPV L1in low-grade cytology (ASCUS and LSIL) is strongly associated with high-grade histopathology diagnoses. In addition, HPV L1capsid protein detection in cervical exfoliated cells don’t rely on the professional cellular pathology doctors.For these reasons, so this study is to explore the clinical significance of HPV L1capsid protein detection in cervical exfoliated cells in high-risk HPV positive women.Objective:To explore the clinical significance of HPV L1capsid protein detection in cervical exfoliated cells in high-risk HPV positive women.Materials and methods:From November2012to June2013,386high-risk HPV positive (Detected by Hybrid capture Ⅱ) women were enrolled as eligible women from Huzhou Maternity&Child Care Hospital and Women’s Hospital, School of Medicine, Zhejiang University. All eligible women underwent Liquid-based cytology (ThinPrep) followed colposcopy. Biopsies were taken if indicated. Cervical exfoliated cells were collected for HPV L1capsid protein detection by immunocytochemistry. Expression of HPV L1capsid protein in groups with different histological diagnosis were compared, and the role of HPV L1capsid protein detection in cervical exfoliated cells in cervical lesion screening was accessed.Results:Total386enrolled eligible women were finally diagnosed histologically as:162normal cervix,94low-grade squamous intraepithelial lesion (LSIL),128high-grade squamous intraepithelial lesion (HSIL) and2squamous cervical cancer (SCC). The positive expression rate of HPV L1in HSIL+(HSIL or worse) group was significantly lower than that in LSIL-(LSIL or better) group (19.2%vs.66.4%, P=0.000). While identifying HSIL+in HPV positive women and compared with cytology, HPV LI detection resulted in significant higher sensitivity (80.8%vs.50.8%, P=0.000) and negative predictive value (NPV)(87.2%vs.76.5%, P=0.004), significant lower specificity (66.4%vs.81.3%, P=0.000), and comparable positive predictive value (PPV)(55.0%vs.57.9%, P=0.619). To identify HSIL+in HPV-positive/cytology-negative women, the sensitivity, specificity, PPV, and NPV of HPV L1detection were87.5%,61.5%,41.2%, and94.1%respectively, and80.0%,86.4%,80.0%and86.4%respectively in HPV-positive/ASCUS(atypical squamous cell of undetermined significance) women.Conclusions:HPV L1capsid detection in cervical exfoliated cells have a role in cervical lesion screening in high-risk HPV positive women, and may be a promising triage for high-risk HPV-positive/cytology-negative or ASCUS women.