With almost 150,000 new cases and 100,000 deaths per year, cervical cancer associated with high risk‐human papillomavirus (HR‐HPV) constitutes a major public health problem in sub‐Saharan Africa, ranking the second most common cause of female cancer incidence and mortality in African women. HPV DNA detection by molecular biology is now recommended as the primary screening method in cervical cancer prevention. HPV viral load, as a potential biomarker, holds significant value for guiding treatment strategies and predicting clinical outcomes.

Recently, the team from the Molecular Epidemiology and Microbial Diversity Laboratory at the School of Science and Technology, University of Nouakchott, published important findings in Health Science Reports. Their results indicate that the accumulated HPV viral load in cervical tissues is associated with the severity of HPV-related cervical lesions. HPV viral load in cervical tissue may serve as a triage tool for invasive cervical cancer (ICC).

Materials and Methods

Between 2022 and 2023, adult women referred to the Centre Hospitalier National, Nouakchott, Mauritania, for suspected high‐grade lesion or cervical cancer were prospectively recruited after informed consent. A total of 50 women diagnosed histologically with either CIN2/3, ADC or SCC, were included in the study. HPV genotyping and quantitative detection were performed using the BioPerfectus HPV21 Kit (BMRT). ROC curves were constructed to evaluate the performance of HPV viral load in predicting high-grade precancerous lesions and invasive cervical cancer (ICC), and to determine the optimal type-specific HPV viral load cutoff for predicting ICC.

Results

HPV‐positive results were detected in 47 biopsies (94.0%), including 12 (85.7%) CIN2/3 and 35 (97.2%) ICC, with 4 ADC and 31 SCC. In all comparisons, except for PO‐HPV plus LR‐HPV, the mean HPV viral loads were significantly higher in ICC than CIN2/3 (p <  0.002 for any HPV; < 0.02 for HR‐HPV; < 0.03 for HR‐HPV plus PO‐HPV; < 0.04 for vaccine HPV) as well as in women older than 50 years (< 0.01). The mean HPV viral loads for any HPV, HR‐HPV and vaccine HPV were significantly higher in ADC than CIN2/3 (p < 0.03, < 0.03 and < 0.04, respectively), as well as in women older than 50 years (< 0.02).

Table 1: Comparison of Cumulative Type-Specific HPV Viral Load in Women with CIN2/3 and ICC

Vaccine HPV genotypes as well as HPV‐39 were more frequently detected in ICC, ADC, SCC than CIN2/3. Mean HPV viral load in SCC and ADC were otherwise similar. Finally, comparisons according to the detected HR‐HPV genotype, especially the two main study HR‐HPV (HPV‐45, HPV‐16) as well as HPV‐45 plus HPV‐16, could not reach statistical significance.

Table 2: Comparison of Cumulative Type-Specific HPV Viral Load for Single and Multiple HPV Genotypes in Women with CIN2/3 and ICC

According to the ROC curve analysis, any HPV viral load had an optimal cutoff of 4.38 copies/10,000 cells (log‐transformed) (95% CI = 3.93–4.79) with Youden's J index of 0.60 (95% CI = 0.34–0.75) and an overall accuracy of 0.78. For HR‐HPV viral load, the optimal cutoff was 4.85 copies/10,000 cells (95% CI = 4.68–4.85) with Youden's J index of 0.54 (95% CI = 0.34–0.65) and an overall accuracy of 0.66. For vaccine HPV, the optimal cutoff was 3.94 copies/10,000 cells (95% CI = 3.13–4.85) with Youden's J index of 0.43 (95% CI = 0.26–0.58) and an overall accuracy of 0.81.

Figure 1: ROC Curves Based on Viral Load of Any HPV (A), HR-HPV (B), and Vaccine-Type HPV Genotypes (C)

Any HPV: HPV-6, -11, -16, -18, -26, -31, -33, -35, -39, -45, -51, -52, -53, -56, -58, -59, -66, -68, -73, -81, and -82
HR-HPV: HPV-16, -18, -31, -33, -35, -39, -45, -51, -52, -56, -58, -59, and -68
Vaccine-Type HPV Genotypes: HPV-6, -11, -16, -18, -31, -33, -45, -52, and -58

Table 3: Sensitivity, specificity, accuracy, and overall performance of cumulative type-specific viral load of Any HPV, HR-HPV, and Vaccine-Type HPV Genotypes for identifying invasive cervical cancer (ICC)

HPV molecular testing is the optimal, most efficient screening approach for both low‐ and high‐ resource settings and has the highest sensitivity and negative predictive values of any known approach to cervical cancer screening. Otherwise, cumulative HPV viral load in cervical tissue may also constitute a relevant biomarker associated with the severity of HPV‐related cervical lesions, and could be used as a triage tool for aggressive ICC in advanced cervical lesions.

Integrating HPV viral load into routine screening promises to optimize resource allocation and diminish the burden of prevention programs by reducing costs, time, and the need for invasive biopsies. Furthermore, viral load monitoring posttreatment for high‐grade cervical lesions (CIN2/3) can detect persistent disease or recurrence, guiding targeted follow‐up and enhancing cost‐effectiveness.

Reference:

Abdoudaim MS, Bélec L, Ahmed MLCB, Baba NDM, Bouassa RM, Abdellahi MVM. Human Papillomavirus Viral Load as Triage Biomarker for High-Grade Cervical Lesions and Invasive Cervical Carcinoma: A Cross-Sectional Study. Health Sci Rep. 2025 Nov 17;8(11):e71524.