Clinical Utility of Human Papillomavirus Genotyping in Cervical Cancer Screening: A Systematic Review

Abstract

Objective Thirteen human papillomavirus (HPV) genotypes are associated with the highest risk of cervical disease/cancer; however, the risk of disease progression and cancer is genotype dependent. The objective of this systematic review was to examine evidence for high-grade cervical intraepithelial neoplasia (≥CIN 3) risk discrimination using HPV genotyping. Materials and Methods A systematic review of English and non-English articles through MEDLINE, Cochrane, clinicaltrials.gov, and abstracts presented at relevant professional society conferences were searched from 2000 to 2019. Search terms included: cervical cancer screening, HPV genotyping, CIN, HPV persistence, humans, and colposcopy; prospective, controlled trials, observational studies, and retrospective studies of residual specimens; evidence included HPV genotyping (beyond genotypes 16/18/45) results. Data were obtained independently by authors using predefined fields. Risk of bias was evaluated with a modified Newcastle-Ottawa Scale. The Grading of Recommendations, Assessment, Development and Evaluation methodology facilitated overall quality of evidence evaluation for risk estimation. The study protocol was registered with the PROSPERO International Prospective Register of Systematic Reviews (CRD42018091093). The primary outcome was CIN 3 or worse risk both at baseline and at different follow-up periods. Results Of 236 identified sources, 60 full texts were retrieved and 16 articles/sources were included. Risk of bias was deemed low; the overall quality of evidence for CIN 3 or worse risk with negative for intraepithelial lesions or malignancies or low-grade squamous intraepithelial cytology was assessed as moderate; that with atypical squamous cells-undetermined significance and “all cytology” was assessed as high. Clinical and methodological heterogeneity precluded meta-analysis. Human papillomavirus genotyping discriminated risk of CIN 3 or worse to a clinically significant degree, regardless of cytology result. Conclusions The evidence supports a clinical utility for HPV genotyping in risk discrimination during cervical cancer screening.

The impact of age and high‐risk human papillomavirus (hrHPV) status on the prevalence of high‐grade cervical intraepithelial neoplasia (CIN2+) in women with persistent hrHPV‐positive, cytology‐negative screening samples: a prospective cohort study

“…[19][20][21] Women who are HPV16/18 positive, even with negative cytology, are more likely to have CIN2+ when compared with women with other hrHPV genotypes. 22 It is currently unclear as to whether HPV16-associated CIN2+ is linked to more obvious aceto-white change or whether the higher prevalence of CIN2+ leads to better colposcopic recognition. This study confirms that women with HPV16, when compared with women with nonHPV16 infections, are more likely to have a high-grade colposcopic impression and higher PPV for biopsy, demonstrating that the performance of colposcopy is HPV genotype dependent.…”

Cervical Cancer Screening Guidelines in the Postvaccination Era: Review of the Literature

“…The risk of progression to severe high-grade CIN and cancer is strongly associated with HPV genotype and genotype-specific persistence. Different oncogenic genotypes entail different risks, with HPV 16 ranking the highest, and HPV 66 the lowest [ 90 ]. Extended genotyping (i.e., assays reporting all 14 high-risk genotypes) enables personalized clinical management for women screened through the primary HPV paradigm.…”

Clinical validation of full genotyping CLART® HPV4S assay on SurePath and ThinPrep collected screening samples according to the international guidelines for human papillomavirus test requirements for cervical screening

“…The value of genotyping is based upon evidence that HPV genotypes have different oncogenic potential [18][19][20][21][22][23]. HPV16 and HPV18 contribute to approximately 70% of all cervical cancers; the five HPV genotypes HPV 31, 33, 45, 52 and 58 are associated with a further 19% of cervical cancers, whereas the remaining six oncogenic HPV genotypes HPV35, 39, 51, 56, 59 and 68 contribute 8-9% [18,24].…”