Abstract
BackgroundThe aim of the study was to investigate the risk of human papillomavirus (HPV) genotyping particularly vaccine genotypes and multiple infections for cervical precancer and cancer, which might contribute to developing genotype-specific screening strategy and assessing potential effects of HPV vaccine.MethodsThe HPV genotypes were identified using the Seq HPV assay on self-collected samples. Hierarchical ranking of each genotype was performed according to positive predictive value (PPV) for cervical intraepithelial neoplasia 2/3 or worse (CIN2+/CIN3+). Multivariate logistic regression model was used to estimate the odds ratios (ORs) with 95% confidence interval (CI) of CIN2+ according to multiplicity of types and vaccine types.ResultsA total of 2811 HPV-positive women were analyzed. The five dominant HPV genotypes in high-grade lesions were 16/58/52/33/18. The overall ranking orders were HPV16/33/35/58/31/68/18/ 56/52/66/51/59/45/39 for CIN2+ and HPV16/33/31/58/45/66/52/18/35/56/51/68/59/39 for CIN3+. The risks of single infection versus co-infections with other types lower in the hierarchy having CIN2+ were not statistically significant for HPV16 (multiple infection vs. single infection: OR = 0.8, 95%CI = 0.6-1.1, P = 0.144) or other genotypes (P > 0.0036) after conservative Bonferroni correction. Whether HPV16 was present or not, the risks of single infection versus multiple infection with any number (2, ≥2, or ≥ 3) of types for CIN2+ were not significantly different. In addition, HPV31/33/45/52/58 covered by nonavalent vaccine added 27.5% of CIN2, 23.0% of CIN3, and 12.5% of cancer to the HPV16/18 genotyping. These genotype-groups were at significantly higher risks than genotypes not covered by nonavalent vaccine. Moreover, genotypes covered by nonavalent vaccine contributed to 85.2% of CIN2 lesions, 97.9% of CIN3 and 93.8% of cancers.ConclusionsPartial extended genotyping such as HPV33/31/58 but not multiplicity of HPV infections could serve as a promising triage for HPV-positive self-samples. Moreover, incidence rates of cervical cancer and precancer were substantial attributable to HPV genotypes covered by current nonavalent vaccination.
Highlights
The aim of the study was to investigate the risk of human papillomavirus (HPV) genotyping vaccine genotypes and multiple infections for cervical precancer and cancer, which might contribute to developing genotype-specific screening strategy and assessing potential effects of HPV vaccine
We showed in a large study that 75.8% of abnormal cytology and 50.9% High-grade Squamous Intraepithelial Lesion (HSIL) cytology were attributed to other High-risk human papillomavirus (hrHPV) infection among HPV-positive women, and 62.7%/43.9% of CIN2/CIN3+ were caused by other hrHPV infection over 3-year follow-up [8]
Genotyping by Seq HPV assay was valuable in improving risk stratification of HPV-positive self-samples, with HPV33/31/58 types ranked high risk and HPV39/59/51 types ranked low risk both for CIN2+/CIN3+
Summary
The aim of the study was to investigate the risk of human papillomavirus (HPV) genotyping vaccine genotypes and multiple infections for cervical precancer and cancer, which might contribute to developing genotype-specific screening strategy and assessing potential effects of HPV vaccine. High-risk human papillomavirus (hrHPV) was found to be a necessary cause of cervical cancer [3], leading to the development of HPV-based screening and vaccine for cervical cancer prevention and control. Information on type-specific risks for cervical diseases may help monitor effectiveness of HPV vaccine, and may aid in the individualized triage plans, for HPV-based screening on self-samples [6]. We showed in a large study that 75.8% of abnormal cytology and 50.9% HSIL cytology were attributed to other hrHPV infection among HPV-positive women, and 62.7%/43.9% of CIN2/CIN3+ were caused by other hrHPV infection over 3-year follow-up [8]. The introduction of vaccines could lead to the eradication of HPV16/18 [9,10,11], better understanding of extended genotyping provides information for establishing favorable screening policies following the introduction of vaccines [12]
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