The Risk Stratification for Cervical Cancer and Precursors of Domestic HPV Testing With HPV 16/18 Genotyping in Women With NILM Cytology in CentralChina: A Cohort Study

Abstract

ObjectiveTo evaluate the clinical performance and utility for risk stratification of DH3 HPV assay in women (≥30 years) with NILM cytology.MethodsA prospective cohort was established in Central China between November 8 to December 14, 2016 which consisted of 2180 women aging 30-64 years with NILM cytology. At baseline, all women were screened using DH3 HPV assay. HPV 16/18 positive women would be assigned to colposcopy and biopsied if necessary. Then, hr-HPV positive women without CIN2+ lesions would be followed up by cytology every 12 months for two years. In the 3rd year of follow up, all women that were not biopsy proven CIN2+ would be called back and screened by cytology again. In follow-up period, women with ASC-US and above were referred to colposcopy and biopsied if clinically indicated. CIN2+ was the primary endpoint in analysis. The clinical performance and utility for risk stratification of DH3 HPV assay were assessed by SPSS 22.0 and SAS 9.4.ResultsOf 2180 qualified women, the prevalence of hr-HPV was 8.5% (185/2180), 45(2.1%) were HPV 16/18 positive. The clinical performance for HPV16/18 was 91.7% for sensitivity, 98.4% for specificity, respectively against CIN2+ detection at baseline. In four years of study, the corresponding rates of HPV 16/18 were 51.5% and 98.7%, respectively. The cumulative absolute risk for the development of CIN2+ was as high as 37.8% for HPV 16/18 positive women, followed by hr-HPV positive (14.6%), other hr-HPV positive (11.0%) and HPV negative (0.3%) in three years. The relative risk was 125.6 and 3.4 for HPV 16/18 positive group when compared with HPV negative and other hr-HPV positive group, respectively.ConclusionsDH3 HPV assay demonstrated excellent clinical performance against CIN2+ detection in cervical cancer screening and utility of risk stratification by genotyping to promote scientific management of women with NILM cytology.

Which is the best management for women with normal cervical cytologic findings despite positivity for non-16/18 high risk human papillomaviruses?

“…Similarly, the observed agreement between the assay and HC2 was 99.2% (κ = 0.938); the reported sensitivity of DH3 for HSIL was equal to that of HC2 (98.67%) ( 84 ). Moreover, this assay showed superior clinical performance in terms of HSIL detection and risk discrimination in Chinese women who were NILM ( 30 ). HPV16/18 genotyping showed high sensitivity (91.7%) and specificity (85.7%) for HSIL detection ( 30 ).…”

“…Moreover, this assay showed superior clinical performance in terms of HSIL detection and risk discrimination in Chinese women who were NILM ( 30 ). HPV16/18 genotyping showed high sensitivity (91.7%) and specificity (85.7%) for HSIL detection ( 30 ). Due to its concurrent HPV16/18 genotyping and non-polymerase chain reaction- (PCR-) based benefits, the DH3 HPV assay may have triage applications in developing countries.…”

“…The fact that HPV16/18 poses a considerable risk for developing HSIL in women who are NILM is well-established in the literature. Women with HPV16/18 infections have a higher risk for HSIL and more advanced lesions than those with non-16/18 HPV infections ( 15 , 30 ). Several observational studies have associated non-16/18 HR-HPVs with an increased risk to cervical preneoplasia ( Table 2 ).…”

“…Two retrospective studies analyzed the odds ratios (ORs) for HSIL in women who were NILM but positive for HR-HPVs ( 26 , 29 ). HPV genotyping is a strong predictor of oncogenic progression risk ( 30 , 32 , 33 ). Longitudinal studies have reported the progression rate of non-16/18 HR-HPVs ( 4 , 18 , 34 ).…”

“…Several innovative screening assays have been introduced, including HPV triage protocols (HPV mRNA and DH3), surrogates for cytology (automated DS cytology), biomarkers (viral load and deoxyribonucleic acid (DNA) methylation), and other technologies (deep learning-assisted visual triage and self-sampling technology). For instance, in China, the DH3 HPV assay, a newly developed RNA–DNA hybrid capture-based technique similar to the Hybrid Capture 2 (HC2), has been utilized (in combination with HPV16/18 genotyping) for cervical cancer screening ( 30 , 84 , 85 ). The clinical performance of the assay in identifying HSIL was comparable to that of the Cobas 4800 HPV and HC2 tests ( 84 , 85 ).…”