A pilot analytic study of a research-level, lower-cost human papillomavirus 16, 18, and 45 test

Abstract

The analytic performance of a low-cost, research-stage DNA test for the most carcinogenic human papillomavirus (HPV) genotypes (HPV16, HPV18, and HPV45) in aggregate was evaluated among carcinogenic HPV-positive women, which might be used to decide who needs immediate colposcopy in low-resource settings (“triage test”). We found that HPV16/18/45 test agreed well with two DNA tests, a GP5+/6+ genotyping assay (Kappa = 0.77) and a quantitative PCR assay (at a cutpoint of 5000 viral copies) (Kappa = 0.87). DNA sequencing on a subset of 16 HPV16/18/45 positive and 16 HPV16/18/45 negative verified the analytic specificity of the research test. It is concluded that the HPV16/18/45 assay is a promising triage test with a minimum detection of approximately 5,000 viral copies, the clinically relevant threshold.

Human Papillomavirus and Cervical Cancer: Biomarkers for Improved Prevention Efforts

“…Most are marked by nonuniformity in determination of end points and limited sample sizes. Other viral markers such as HPV L1 capsid protein [99–101] and E6 oncoprotein detection [102,103] have been evaluated in a limited number of small studies, but more evidence is needed to determine their utility.…”

“…Yet, further research on adaptation of these strategies is needed to avoid overtreatment, given the different age distributions of HPV prevalence worldwide [110]. Novel biomarkers that reflect measurement of an advanced disease process end point, such as overexpression of p16 ink4a or HPV E6 protein detection [102,103], are also being evaluated in these settings, with the goal of achieving an optimal balance of sensitivity and specificity for very infrequent testing. Additional efforts are also being undertaken to evaluate biomarker assays using noninvasive and user-operated screening methods (e.g., self-sampling or urine-based sampling) that can address challenges in improving access to cervical cancer prevention services in these settings.…”

Cervical Cancer Prevention in Low- and Middle-Income Countries: Feasible, Affordable, Essential

“…In comparison with other screening methods, HPV screening was superior in helping reduce both the incidence and mortality of cervical cancer in a large community-based randomized trial (18). With the ongoing development of low-cost, rapid molecular-assay technologies for HPV that are robust for field operations (19, 20), HPV-based screening has the promise to become a frontline method for cervical cancer screening to maximize detection and expand access across LMICs. Integrating HPV testing with VIA-based “see-and-treat-or-refer” platforms can combine the high accuracy of HPV DNA testing with the same-visit benefit of triage by VIA-based screening (21–23).…”