Human Papillomavirus Same Genotype Persistence and Risk: A Systematic Review

Abstract

Objective: The aim of the study was to examine whether high-grade cervical intraepithelial neoplasia (CIN) was more closely associated with human papillomavirus (HPV) same-genotype persistence (SGTP) versus clearance of prior infection with a subsequent infection by a new genotype (genotype switch [GS]), clearance of HPV infection, or acquisition of a new HPV infection after a negative infection status, during a follow-up testing subsequent to abnormal screening results.

Materials and methods: MEDLINE, Cochrane Library, Health Technology Assessment, and clinicaltrials.gov were searched from January 2000 to July 2019 for prospective controlled trials and observational studies of women and retrospective studies using HPV assays with extended- or full-genotype reporting. The primary outcome was high-grade CIN after at least 2 rounds of testing. Overall quality of evidence for the risk estimate outcomes was assessed. Of the 830 identified abstracts, 66 full-text articles were reviewed, and 7 studies were included in the synthesis. The study protocol was registered with the PROSPERO International Prospective Register of Systematic Reviews (CRD42018091093).

Results: Continued HPV-positive women falls in 2 equally large groups: SGTP and GS. Sensitivity, positive predictive value, and positive likelihood ratio of SGTP were significantly higher than for GS. Human papillomavirus genotypes may be ranked into 3 tiers (immediate colposcopy, follow-up testing, return to routine screening), according to associated risk of persistence for high-grade CIN and to prevailing clinical action thresholds.

Conclusions: There is moderately high-quality evidence to support the clinical utility of SGTP to improve risk discrimination for high-grade CIN compared with qualitative HPV testing without genotype-specific information.

FIGURE 1

The PRISMA flow diagram detailing the process of search and selection. Article search and selection occurred over 4 stages (identification, screening, eligibility, and included). Selection began with 830 abstracts, and after exclusion of duplicates (n = 58), removal based on exclusion criteria (n = 686), removal based on outcomes missing (n = 21), missing pre/post data (n = 18), missing genotyping (n = 14), testing interval too large (n = 2), and not original research (n = 1) resulted in 10 articles included for this systematic review.

FIGURE 2

Cumulative incident risk for high-grade cervical disease according to HPV status at the first and subsequent test. Five HPV status classifications are shown, including HPV negative (purple; negative at first and subsequent testing), HPV clearance (blue; HPV positive at first test and HPV negative at second test), new HPV infection (green; HPV negative at first test and HPV positive at the subsequent test), pooled (any genotype) HPV persistence (yellow; any HPV genotype at first test and any HPV genotype at the subsequent test), and genotype-specific HPV persistence (red; positive for the same genotype at the first and subsequent test). Risk estimation, plotted along the y-axis and based on HPV status, is shown in (a) for CIN 2 or higher and CIN 3 or higher over 3 years, in (b) for CIN 3 or higher among individuals with normal and low-grade cytology across 5-years, and in (c) for CIN 3 or higher among individuals with normal and low-grade cytology across 10 years. The disease outcome, 5-, and 10-year time points.