Screening guideline originators (WHO, ASCO, country-specific) have not yet included an analysis of the body of science published during the last decade about the clinical value of extended HPV genotyping (xGT) in cervical cancer screening and triage, needed to support guideline panels’ recommendations. This targeted systematic review addresses key questions (KQ) that pertain to the effectiveness of including xGT results with screening for reducing cervical cancer mortality and incidence. KQ1 compares xGT versus partial genotype reporting/masking of a pool of other genotypes. KQ2 evaluates xGT as triage of primary HPV positive results, of ASCUS cytology, and as triage of cotesting.
We searched the Database of Abstracts of Reviews of Effects, Cochrane Database of Systematic Reviews, PubMed, and the Health Technology Assessment database from 2000 through 2017 for relevant controlled trials and observational studies. We supplemented by hand-searching of retrieved article reference lists. Eligible studies included prospective studies of women and retrospective studies of residual specimens from women that were screened or tested using human papillomavirus DNA tests. The reference standard was cervical intraepithelial neoplasia 2 (CIN2) or CIN3 or CIN2+ or CIN3+ or invasive cervical cancer (squamous and/or adenocarcinoma). The timeframe was baseline, or 1-year, or 3-year, or 5-year, or greater than 5-year. Relevance screening, data extraction, risk of bias analyses, and quality assessments were performed. Critical appraisal methodology used design-specific quality criteria from the QUADAS evidence-based quality assessment tool of diagnostic accuracy studies, supplemented by the STARD checklist and GRADE methodology.
The available evidence supports the conclusion that reporting xGT results supports discrimination of both current and future CIN2+ risks. Guideline panels must decide whether to separate reporting by individual genotypes or to group genotypes with similar risks into risk tiers. Based on large studies, xGT appears very promising as triage in all screening paradigms to discriminate risk and support risk-based clinical action steps by the principle of equal management for equal risk. Models for different screening paradigms, including routine screening interval, enhanced screening interval, referral to colposcopy, and treatment are described. The information in this report is intended to help guideline panels, policymakers, clinicians, and women make informed decisions about the selection of health care screening and diagnostic services, is intended as a reference, and not as a substitute for clinical judgment.