Extensive HPV Genotyping Reveals High Association between Multiple Infections and Cervical Lesions in Chinese Women

Abstract

Objective. The relationship between human papillomavirus (HPV) and cervical lesions has been extensively elucidated, but infection with multiple genotypes is less investigated due to methodology limitations. In the current study, with a method of genotyping 21 HPVs in a routine cervical screening population, we aimed to investigate the prevalence and diversity of HPV infections in Chinese women and further evaluate the impact of multiple infections of HPV on cervical lesion progression. Methods. Totally, 73,596 patients who underwent 21-genotype HPV testing from January 2018 to April 2019 were retrieved from the database of the Department of Pathology, Obstetrics and Gynecology Hospital of Fudan University. HPV testing was performed by real-time PCR assay, including 13 high-risk HPVs (hrHPV), 5 potential hrHPVs, and 3 low-risk HPVs. Results. Of the 17,079 (infection rate, 23.2%) hrHPV- or potential hrHPV- (hr/phrHPV-) positive cases, 26.3% had multiple infections. Women younger than 25 and older than 65 were more prone to multiple infections. Of the hr/phrHPV-positive cases involving cervical intraepithelial neoplasia (CIN) 2 or worse (CIN2+), HPV73, 53, and 66 (=59) were the top three genotypes most likely to be included in multiple infections, while HPV16, 18, and 58 were the 3 least. Patients with single infection of HPV16 had higher incidences of CIN2+ than those with multiple-infection pattern ( P < 0.001 ), indicating that mixing with other genotypes alleviated pathogenicity. The infection of HPV52, 53, 56, 51, 39, 66, 59, 68, and 35 showed an opposite pattern, indicating that they were less likely to be pathogens individually. All other types showed no significant differences, indicating the capability of pathogenesis independently. HPV26 showed a higher OR for CIN2+ than most traditional hrHPV genotypes. The vial load and the percentage of HPV16 showed positive correlation with the severity of cervical lesions. Conclusion. Extensive genotyping identified 3 most frequent genotypes, HPV16, 52, and 58, in CIN2+ of Chinese population. HPV16 mixing with other genotypes alleviated its pathogenicity. The vial load and the percentage of HPV16 were positively correlated with the severity of cervical lesions. HPV26 may be considered as a hrHPV, which needs to be evaluated and confirmed by more cases.

Evaluating the Feasibility of Machine-Learning-Based Predictive Models for Precancerous Cervical Lesions in Patients Referred for Colposcopy

“…In total, 33.2% of HR-HPV-positive patients were infected with multiple HR-HPVs in our study, which is within the range of 26.3% and 43.2% that has been previously reported [ 32 , 33 ]. We found that a higher incidence of HSIL+ in patients with single infections than those with multiple infections.…”

“…Other data highlight the importance of the type of HPV infection. For example, a single infection with HPV 16 is more virulent than a multiple-infection pattern, while for HPVs 52, 53, 56, 51, 39, 66, 59, 68, and 35, a multiple-infection pattern is more likely to develop into HSIL+ than a single infection [ 32 ].…”

Coinfection of HPV18 with some high-risk less frequent HPV subtypes

“…HPV18 and HPV31 were categorized under the 5 most common HPV genotypes that affect women worldwide (Pimple and Mishra, 2022). Moreover, HPV18 and HPV16 are the most potent strains that are responsible for over 70% of the cases of cervical and head, and neck cancers worldwide (Yu et al, 2022). The most potent oncogenes associated with HPV 18 are E6/E7 (Tian et al, 2022).…”

“…Persistent infection with HR-HPV genotypes represents the major concern about cervical cancer burden in these regions. HR-HPV subtypes 16, 18, 31, 58, and HR-HPV subtypes include 16,18,31,33,45,35,52,56,39,51,68,and 59. Moreover,HPV 53,66,26,73, and 82 are regarded as potential HR-HPV subtypes (Zhong, et al, 2022).…”

“…HR-HPV subtypes 16, 18, 31, 58, and HR-HPV subtypes include 16,18,31,33,45,35,52,56,39,51,68,and 59. Moreover,HPV 53,66,26,73, and 82 are regarded as potential HR-HPV subtypes (Zhong, et al, 2022). World Health Organization (WHO) has reported that cervical cancer represented 0.08% of all deaths in Yemen (World health Ranking, 2020).…”