Human Papillomavirus Viral Load as Triage Biomarker for High-Grade Cervical Lesions and Invasive Cervical Carcinoma: A Cross-Sectional Study

Abstract

Background and aims: We herein evaluated whether intra-tissue HPV viral load may constitute a triage biomarker to differentiate between high-grade precancerous cervical lesions from intra cervical cancer (ICC).

Methods: 50 biopsy samples prospectively obtained from women living in Mauritania suffering from high-grade cervical intraepithelial neoplasia (CIN2/3), adenocarcinoma (ADC) or squamous cell carcinoma (SCC) were analysed for HPV genotyping and quantitation carried out using Bioperfectus Multiplex Real Time Human Papillomavirus Genotyping Real Time PCR assay.

Results: HPV-positive results were detected in 47 biopsies (12 CIN2/3 and 35 ICC, including 4 ADC and 31 SCC). The cumulative HPV viral loads of any HPV and high risk-HPV (HR-HPV) in ICC were significantly higher than those in CIN2/3 (p < 0.002 for any HPV; 0.02 for HR-HPV). The cumulative viral loads of any HPV and HR-HPV possessed a good discriminatory ability to differentiate between CIN2/3 and ICC, with optimal cutoffs ranging from 4.38 (any HPV) to 4.85 (HR-HPV) copies per 10,000 cells.

Conclusion: Our observations show that cumulative HPV viral load in cervical tissue may constitute a relevant biomarker associated with the severity of HPV-related cervical lesions. HPV viral load in cervical tissue could be used as a triage tool for aggressive ICC in advanced cervical lesions.

Keywords: HPV; HPV viral load; cervical cancer; cervical pathology; mauritania; multiplex real‐time PCR.

Figure 1

Empirical ROC curves drawn from any HPV (A), HR‐HPV (B) and vaccine HPV (C) viral load data for identifying ICC from high‐grade precancerous and cancerous lesions. The AUC are draw with the 95% confidence bounds (hatched grey area). The most useful cutoff of the optimal viral load level to predict ICC is calculated according to each ROC curve (full circle). The 45° diagonal line serves as the reference line. Any HPV include the following HPV genotypes (HPV‐6, −11, −16, −18, −26, −31, −33, −35, −39, −45, −51, −52, −53, −56, −58, −59, −66, −68, −73, −81, and −82); High risk‐HPV (HR‐HPV) include the following HR‐HPV genotypes (HPV‐16, −18, −31, −33, −35, −39, −45, −51, −52, −56, −58, −59, and − 68); Gardasil‐9® vaccine HPV include the following HPV genotypes (HPV‐6, −11, −16, −18, −31, −33, −45, −52, and −58). AUC: Area under the ROC curve; HR‐HPV: High risk‐HPV; ICC: Invasive cervical cancers; ROC: Receiver operating characteristics.