Roles of extended human papillomavirus genotyping and multiple infections in early detection of cervical precancer and cancer and HPV vaccination

The 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.
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Roles of extended human papillomavirus genotyping and multiple infections in early detection of cervical precancer and cancer and HPV vaccinationSongetal. BMC Cancer (2022) 22:42https://doi.org/10.1186/s12885-021-09126-3 RESEARCH Open AccessRoles ofextended human papillomavirusgenotyping andmultiple infections inearlydetection ofcervical precancer andcancerandHPV vaccinationFangbinSong1,2,3†, PeishaYan1,2,3†, XiaHuang1,2,3, ChunWang1,2,3, HuiDu1,2,3*, XinfengQu4*and RuifangWu1,2,3*  Abstract  Background:  The 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. Methods:  The HPV genotypes were identified using the Seq HPV assay on self-collected samples. Hierarchical rank- ing 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. Results:  A 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 nonava- lent 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. Conclusions:  Partial 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.*Correspondence: duhui_107108@163.com; steve1005@icloud.com;wurfpush@126.com† Fangbin Song and Peisha Yan contributed equally to this work.3 Shenzhen Key Laboratory onTechnology forEarly Diagnosis ofMajorGynecological Diseases, Shenzhen518036, Guangdong, P. R. China4 Sanming Project ofMedicine inShenzhen, Peking University ShenzhenHospital, Shenzhen518036, Guangdong, ChinaFull list of author information is available at the end of the article © The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://​creat​iveco​mmons.​org/​licen​ses/​by/4.​0/. The Creative Commons Public Domain Dedication waiver (http://​creat​iveco​ mmons.​org/​publi​cdoma​in/​zero/1.​0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.Songetal. BMC Cancer (2022) 22:42 Page 2 of 13 Key ...