Epidemiological study of HPV infection in Shanghai: a population study based on screening for HPV infection

Epidemiological study of HPV infection in Shanghai: a population study based on screening for HPV infection | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Epidemiological study of HPV infection in Shanghai: a population study based on screening for HPV infection Xiaoping Gu, Yijie Tang, Dandan Yang, Qinghui Xie, Lingling Fu, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8899569/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 5 You are reading this latest preprint version Abstract Human papillomavirus (HPV) infection is the primary cause of cervical cancer (CC). Although the HPV vaccination rate has been increasing, the HPV infection rate remains persistently high. Therefore, understanding the epidemiological patterns of HPV is crucial for controlling its infection and transmission. To investigate the HPV epidemiological characteristics and its association with cervical epithelial abnormalities, 21,188 individuals who underwent HPV testing between September 2023 and September 2025 were enrolled. The overall HPV positivity rate was 55.09%, with a higher infection rate in females than in males, and the infection rate increased with age. HPV infections often occurred in the form of mixed infections, which accounted for 50.91% of all positive samples, mainly involving 2 to 3 subtypes. Among the top five most prevalent HPV subtypes, HPV06 and HPV31, both low-risk genotypes, were the most common single infection types and also the most frequently involved in mixed infections. HPV31, HPV45, and HPV16 were the most common high-risk subtypes, and their infections tended to present as mixed infections. HPV infection and mixed infection rates were positively correlated with lesion severity: 94.12% (68.75% mixed) in ASC-H, 90.63% (58.62% mixed) in LSIL, 77.55% (55.26% mixed) in ASC-US, and 65.20% (37.07% mixed) in NILM. HPV16/18 exhibited a strong association with high-grade lesions. These results confirm age- and gender-specific HPV distribution patterns, emphasizing the role of high-risk subtypes and mixed infections in lesion progression, and support the need for tailored screening, vaccination, and risk-stratified management. Human papillomavirus Subtype distribution Mixed infection Cervical lesions Figures Figure 1 Figure 2 Figure 3 Introduction Cervical cancer (CC) is a common gynecological cancer and a major cause of cancer-related deaths. Globally, in 2020, there were 604,127 CC cases registered, 341,831 leading to death. Age-standardized incidences are 13.3/100,000 women-years, and mortality rates are 7.2/100,000 women-years [ 1 ]. In China, CC contributed an estimated 109,741 cases and 59,060 deaths in women according to a secondary analysis of the GLOBOCAN 2020 data [ 2 ]. Human papillomavirus (HPV) is the most common sexually transmitted pathogen worldwide, and its global incidence is increasing. Sexual intercourse is the main route of transmission. HPV infection can cause a variety of female genital tract diseases, such as anogenital warts, cervical intraepithelial neoplasia, and CC [ 3 , 4 ]. Research estimates that about 80% of sexually active women will contract HPV at some stage in their lives. More than 90% of individuals can clear the virus through their immune system. However, persistent HPV infection can lead to CC without timely treatment. More than 200 genotypes of HPV have been identified. HPV types can be classified into low-risk and high-risk strains depending on their oncogenic potential. Persistent infection with high-risk HPV is a key driver of cervical cancer, which remains a major contributor to global cancer-related morbidity and mortality in women [ 5 , 6 ]. Notably, HPV16 and HPV18 are the most prevalent high-risk-HPV types, responsible for 70% of CC. In contrast, low-risk HPV types mainly cause warts of the genitals, anus, mouth, throat, and oropharyngeal tumours [ 7 ]. Given the high prevalence of HPV and its heavy disease burden, understanding the epidemiological characteristics of HPV and their relationship with clinical manifestations is essential for targeted prevention and clinical management. The aim of this study was to clarify the status of HPV infection and HPV subtypes among women of different age groups in Shanghai. Our findings can be useful in developing effective measures and approaches to preventing infection with both high- and low-risk HPV subtypes. To better understand the prevalence of HPV infection among women in Shanghai, we collected and analyzed data of all age groups who underwent HPV testing at Shanghai Skin Disease Hospital in Shanghai. Materials and methods Specimen collection and preservation Before collecting the sample, gently wipe off excessive secretions around the cervix using a cotton swab. Insert the cervical sampling brush into the junction of the squamous and columnar epithelium at the cervix opening, and rotate it clockwise or counterclockwise for 3–5 turns to collect cervical exfoliated cells. Place the collected cells into a sampling tube labeled with the patient’s identification number and seal it tightly for submission. After specimen collection, it should be promptly tested. Specimens stored at a temperature of 2–8℃ should be tested within 3 days, while specimens stored at -20℃ should be tested within 12 months. The specimen should be avoided from repeated freezing and thawing, with a maximum of 5 cycles. If using an ice pack for transportation, it should not exceed 3 days. This study has been reviewed and approved by the Ethics Committee of Shanghai Skin Disease Hospital, No. 2025-52 (Departmental). HPV genotyping Cervical samples were collected with a cytobrush for genomic DNA extraction. After vortexing, 350 µL of the sample was used with a nucleic acid extraction reagent, and HPV DNA was extracted via a nucleic acid extractor.1 µL DNA was mixed with 24 µL amplification reagent, centrifuged, and subjected to PCR: denaturation at 20℃ for 10 min, and 95℃ for 9 min. Followed by 40 cycles at 95℃ for 20 s, 55℃ for 30 s, and 72℃ for 30 s, and finally extension at 72℃ for 5 min. For PCR, block the membrane with blocking solution twice, then add enzyme-labeled solution at 25℃ for 3.5 min. After pumping out, set to 36℃, wash with Solution A four times, add chromogenic solution for 3–5 min, pump out, wash with Solution B three times and distilled water, then remove the membrane and analyze results within an hour. During PCR product hybridization, preheat the hybridization solution to 45℃, prepare the instrument, denature the PCR product at 95℃, then ice-water bath, and perform hybridization at 45℃ with preheated solution, maintaining the temperature throughout. ThinPrep cytologic test (TCT) Specimens positive for HPV genotyping were directly used for TCT. Two experienced cytopathologists diagnosed the liquid cytology specimens independently.If their diagnoses differed, a third cell pathologist reviewed the sample. Cytological results were classified according to the Bethesda System. The classification included five categories: negative for intraepithelial lesion and malignancy (NILM), atypical squamous cells of undetermined significance (ASC-US), atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion (ASC-H), low-grade squamous intraepithelial lesion (LSIL), and high-grade squamous intraepithelial lesion (HSIL) [ 8 , 9 ]. Statistical analysis Data were analysed using GraphPad Prism 9.0 software. The HPV positivity rate was expressed as a percentage. Count data was used to calculate the number of positive and negative cases for each type of HPV. A chi-square test was performed to determine if there were statistically significant differences between the two groups. The χ 2 test was applied to compare the infection rate of different age groups and the infection rate of HPV genotyping according to additional TCT classifications. Differences were considered statistically significant if the difference was P < 0.05. Results Result 1. Epidemiological Characteristics of HPV Infection. The prevalence of HPV infection was analyzed across different age groups and between males and females, as presented in Table 1 . Among all 21,188 participants, the overall HPV infection rate was 55.09% (95% CI: 54.38–55.80). Females exhibited a significantly higher HPV infection rate (65.31%, 95% CI: 64.21–66.41) than males (52.52%, 95% CI: 51.80-53.24). Regarding age stratification, the HPV infection rates showed an upward trend with increasing age in both genders. For males, the infection rate was 53.15% (95% CI: 51.72–54.58) in the ≤ 30 years group, 54.02% (95% CI: 52.78–55.26) in the 31–40 years group, 54.29% (95% CI: 52.63–55.95) in the 41–50 years group, 59.28% (95% CI: 56.38–62.18) in the 51–60 years group, and peaked at 55.02% (95% CI: 52.05–57.99) in the ≥ 60 years group. Table 1 HPV infection at different Ages and Gender. Age group (years) Sex Total number of cases Number of infections Percentage (%) Total (%) 95% CI Male Female Male Female Male 95% CI Female 95% CI ≤ 30 4395 1604 2336 910 53.15 51.72–54.58 56.74 54.30-59.18 54.08 52.85–55.31 31–40 5335 2739 2882 1509 54.02 52.78–55.26 55.09 53.44–56.74 54.38 53.35–55.41 41–50 3122 1259 1695 687 54.29 52.63–55.95 54.57 51.85–57.29 54.37 52.98–55.76 51–60 1083 473 642 288 59.28 56.38–62.18 60.89 56.63–65.15 59.77 57.12–62.42 ≥ 60 1036 422 570 339 55.02 52.05–57.99 80.33 76.61–84.05 59.98 56.94–63.02 Total 15472 5716 8125 3733 52.52 51.80-53.24 65.31 64.21–66.41 55.09 54.38–55.80 For females, the infection rate increased markedly with age, ranging from 56.74% (95% CI: 54.30-59.18) in the ≤ 30 years group to 80.33% (95% CI: 76.61–84.05) in the ≥ 60 years group, which was the highest infection rate across all subgroups. The total HPV infection rate in each age group was 54.08% (≤ 30 years), 54.38% (31–40 years), 54.37% (41–50 years), 59.77% (51–60 years), and 59.98% (≥ 60 years), respectively, with a gradual elevation as age advanced. Result 2. Age Distribution of High and Low Risk HPV Subtypes. HPV06 exhibited the highest prevalence, with an infection rate of 9.515%, demonstrating a substantial predominance over all other detected subtypes. Other relatively prevalent genotypes comprised HPV71, HPV31, HPV45, HPV16, and HPV68, as illustrated in Fig. 1 . Within high-risk HPV genotypes, the top five most prevalent types were HPV31, HPV45, HPV16, HPV68, and HPV58, indicating a potential correlation between these specific subtypes and CC among patients in the Shanghai region. The distribution and mixed-infection status of the top 10 high-risk and low-risk HPV subtypes are presented in Table 2 . Of all listed subtypes, HPV06, a low-risk genotype, had the largest number of total positive samples (2016) and the highest mixed-infection rate (34.40%). HPV71 and HPV31 were the second and third most prevalent, with mixed-infection rates of 32.19% and 30.85%, respectively. Among the top 10 HPV subtypes, six were high-risk genotypes, namely HPV31, HPV45, HPV16, HPV68, HPV58, and HPV52, whose mixed-infection rates ranged from 25.41% to 29.72%. The remaining four subtypes were low-risk, including HPV06, HPV71, HPV43, and HPV42, with mixed-infection rates between 26.20% and 34.40%. Overall, low-risk HPV subtypes tended to exhibit higher mixed-infection rates compared with high-risk subtypes in this study. Table 2 The high-risk of HPV subtype mixed-infection Rank HPV Subtype Risk Category Total Positive Samples Mixed-infection Samples 1 HPV06 Low-risk 2016 34.40% 2 HPV71 Low-risk 1187 32.19% 3 HPV31 High-risk 1167 30.85% 4 HPV45 High-risk 1090 29.72% 5 HPV16 High-risk 1012 28.65% 6 HPV68 High-risk 977 27.94% 7 HPV58 High-risk 922 26.89% 8 HPV43 Low-risk 905 26.52% 9 HPV42 Low-risk 897 26.20% 10 HPV52 High-risk 862 25.41% Result 3. Severity Distribution of HPV Mixed Infections. Table 3 illustrates the profile of HPV mixed infection according to the number of concurrent subtypes. Among the 5,862 identified mixed infection cases, dual-subtype infection represented the dominant form, with a proportion of 55.35%. The proportion of cases gradually decreased as the number of infected subtypes increased: 28.81% for 3 subtypes, 11.14% for 4 subtypes, 3.43% for 5 subtypes, and only 1.28% for 6 or more subtypes. The mean number of coinfected subtypes across all mixed infection cases was 2.6, and the average number of infected subtypes in the 6 or more subtypes group was 6.8. Table 3 The status of HPV subtype mixed-infection Number of Subtypes in Mixed Infection Number of Cases Percentage of Mixed Infections (%) Average Number of Infected Subtypes 2 Subtypes 3245 55.35 - 3 Subtypes 1689 28.81 - 4 Subtypes 653 11.14 - 5 Subtypes 201 3.43 - 6 + Subtypes 75 1.28 6.8 (Average) Total 5862 100 2.6 To better investigate which HPV subtype is more prone to mixed infection, we conducted a further analysis of mixed infection status. The results showed that all mixed infection cases, HPV06 was the most frequently involved subtype, accounting for 13% of the total mixed-infection count, which was higher than any other genotype (Fig. 2 ). The next common subtypes included HPV71 and HPV31, each accounting for 7%, followed by HPV45 and HPV16 with 6% respectively. In addition, HPV58, HPV43, HPV42 each accounted for 5%, while HPV70, HPV26, HPV44 accounted for 3% individually. The remaining subtypes such as HPV66, HPV59, HPV56, HPV55, HPV33, HPV11, HPV53 and HPV52 each constituted 4% of the mixed infections. Result 4. HPV Mixed Infection Prevalence, Subtype Distribution and High-Risk Co-Infection Tendencies To evaluate the association between pathological results and HPV infection profiles, we analyzed the HPV infection rates and mixed infection patterns across different cervical lesion categories. As presented in Table 4 , distinct differences were observed in HPV infection characteristics among various lesion types. LSIL, the HPV infection rate reached 90.63% (29/32 cases), with 58.62% of HPV-positive cases exhibiting mixed infections. In the ASC-H subgroup, the HPV infection rate was even higher at 94.12% (16/17 cases), and 68.75% of these positive cases had mixed infections, indicating the highest viral complexity among all groups. In the ASC-US cohort, the HPV infection rate was 77.55% (38/49 cases), with 55.26% of positive cases showing mixed infections. Notably, among the NILM group, despite the absence of significant pathological changes, the HPV infection rate still reached 65.20% (669/1026 cases), and 37.07% of these positive cases had mixed infections. These findings collectively demonstrate a positive correlation between the severity of cervical lesions and HPV infection rates, as well as the proportion of mixed infections. The high HPV infection rates and mixed infection ratios in LSIL and ASC-H groups suggest a strong association between persistent or complex HPV infections and the progression of cervical lesions. Even in the NILM group, the considerable HPV infection rate highlights the latent risk of future lesion development, emphasizing the importance of continuous HPV surveillance in this population. Table 4 The relationship between high-risk genotypes and TCT results in HPV-positive specimens Lesion Type Number of Cases HPV Infection Cases HPV Infection Rate (%) Mixed Infection Ratio (Among Positive Cases) LSIL 32 29 90.63 58.62 ASC-H 17 16 94.12 68.75 ASC-US 49 38 77.55 55.26 NILM 1026 669 65.20 37.07 To illustrate the distribution of high-risk HPV genotypes across different cervical lesion groups, we analyzed the infection rates of six prominent subtypes (HPV16, HPV18, HPV31, HPV45, HPV58, and HPV68) in LSIL, ASC-H, ASC-US, and NILM populations, as presented in Fig. 3 . For HPV16, the highest infection rate was observed in ASC-H (56.00%), followed by LSIL (38.00%), ASC-US (32.00%), and NILM (10.00%). HPV18 showed the strongest association with ASC-H (32.00%), while its infection rates in LSIL (21.00%), ASC-US (14.00%), and NILM (3.00%) were relatively lower. HPV31 exhibited a high infection rate in ASC-H (44.00%), followed by LSIL (31.00%), ASC-US (27.00%), and NILM (12.00%). For HPV45, ASC-H (26.00%) and ASC-US (22.00%) had comparable infection rates, with LSIL (18.00%) and NILM (10.00%) showing lower rates. HPV58 was most prevalent in ASC-H (38.00%), followed by LSIL (28.00%), ASC-US (24.00%), and NILM (9.00%). Similarly, HPV68 had the highest infection rate in ASC-H (26.00%), with LSIL (25.00%), ASC-US (19.00%), and NILM (9.00%) showing decreasing trends. Collectively, these data demonstrate that high-risk HPV subtypes, particularly HPV16, HPV31, and HPV58, have a strong association with ASC-H and LSIL, indicating their potential role in driving cervical lesion progression. Even in NILM, the detectable infection rates of these subtypes highlight the latent risk of future pathological changes, underscoring the importance of targeted surveillance for these high-risk genotypes across all lesion categories. Discussion In China, the low vaccination rate has resulted in a persistently high prevalence of HPV infection [ 10 , 11 ]. The prevalence and genotypic distribution of HPV vary with living environment, social behavior, and other factors [ 12 ]. Understanding the profile of HPV infection in Shanghai is crucial for the development of targeted strategies for the prevention and control of CC [ 13 ]. The present study provides a comprehensive characterization of HPV epidemiology in a large cohort of 21,188 individuals, encompassing age and gender-specific distribution, subtype prevalence, infection patterns, and associations with cervical epithelial abnormalities. These findings offer critical insights into HPV transmission dynamics, disease burden, and implications for clinical management and public health strategies. The infection rate in males showed little correlation with age, with an overall infection rate of 52.52%. This infection rate was much higher than that in the population study of Xuhui District, Shanghai, which may be attributed to the fact that the sample-collecting hospital is a dermatological hospital with a more concentrated patient population[ 14 ]. The infection rate in females increased continuously with age, and when females were ≥ 60 years old, the overall infection rate reached as high as 80.33%. Notably, the ≥ 60 years group exhibited a significantly higher infection rate than the 41–50 years group, emphasizing the need for continued HPV screening in postmenopausal women, who are often overlooked in current guidelines despite their elevated risk of persistent infections. High infection rates in younger adults reflect increased sexual activity and recent HPV acquisition, while the rebound in older age groups is attributed to immune senescence, reactivation of latent infections, or new sexual exposures. Among the infected population, mixed infections accounted for 55.35%, indicating that half of the patients were infected with two or more HPV subtypes. The most common subtypes were HPV06, HPV71, HPV31, HPV45, and HPV16. The top two infected subtypes were both low-risk genotypes, and these two subtypes were common in mixed infections, while HPV31, HPV45, and HPV16 were high-risk subtypes. This is slightly different from the subtypes in other regions, where high-risk subtypes such as HPV16, HPV52, and HPV58 are often the most common infected subtypes [ 15 , 16 ]. This may be due to the fact that the hospital mainly treats patients with skin diseases, while low-risk HPV subtypes are mainly associated with skin lesions. This large-scale HPV screening study focused on women in the region, with findings closely tied to the uniqueness of the research population. Notably, the overall HPV infection rate among the regular screening cohort was higher than the data from general outpatient clinics of some comprehensive hospitals [ 17 , 18 ]. This discrepancy may be attributed to the sample source, as the positivity rate among women attending gynecological clinics is generally higher than that among those undergoing routine health check-ups [ 19 – 21 ]. We noticed that the infection rate among males showed little variation across all age groups and was much higher than the data reported in other studies, all exceeding 50%. HPV infection in males was often accompanied by infections with other pathogens, accounting for approximately 74.4% [ 22 ]。In others research, HPV DNA was detected in 19.4% (6/31) of the semen samples [ 23 ]. HPV16 DNA was detected in peripheral blood leukocytes of individuals with HPV-positive seminal samples, indicating that HPV infection may not be confined solely to the lesion sites in males [ 24 ]. Studies have shown that the infertility rate in men with HPV DNA-positive semen is four times higher than that in HPV DNA-negative men [ 25 ]. This finding may be associated with the increasing incidence of infertility in China. The distribution of HPV genotypes in the present cohort exhibited distinct subtype-specific patterns that align with global epidemiological trends while reflecting regional characteristics[ 26 , 27 ]. High-risk HPV subtypes, especially HPV16, 31, 45, and 58, were predominant in younger males. Among men aged 31–40 years, HPV16 was the most common subtype, consistent with its role as the leading oncogenic type worldwide, which is responsible for approximately 50% of CC cases. Notably, HPV58, a subtype highly prevalent in East Asian populations, showed substantial infection rates in both LSIL (28.00%) and ASC-H (38.00%), emphasizing its region-specific carcinogenic potential that warrants increased attention in vaccination and screening strategies. The high frequency of mixed HPV infections is consistent with recent reports and carries significant clinical implications [ 28 ]. Co-infections with 2–3 HPV subtypes were predominant, indicating frequent interactions among HPV types within the genital tract that may affect viral persistence, oncogenic potential, and treatment response. High coinfection rates of oncogenic subtypes with other high-risk subtypes may confer additive or synergistic carcinogenic effects, as exemplified by HPV18 mixed-infection with HPV16 or HPV31, which contributes to the aggressive behavior of cervical adenocarcinomas. The strong correlation between cervical lesion severity and HPV infection rates, particularly mixed infections, further supports the causal role of HPV in cervical carcinogenesis. Nearly universal HPV positivity in ASC-H (94.12%) and high mixed infection rates in LSIL (58.62%) and ASC-US (55.26%) underscore the importance of HPV testing in triaging abnormal cytology. Detection of high-risk subtypes in NILM women highlights latent lesion risk and supports extended follow-up. The predominance of specific subtypes in precancerous lesions informs risk-stratified management, with aggressive intervention for high-risk combinations and observation for low-risk infections. In conclusion, this large-scale study provides a contemporary epidemiological profile of HPV infection, highlighting age- and gender-specific patterns, subtype distribution, and mixed infection dynamics. These findings highlight the necessity of personalized screening and vaccination strategies. They prioritize younger males for the prevention of high-risk HPV-related malignancies and older females for cervical cancer prevention.These results also emphasize the complexity of HPV-associated diseases and support further research into the mechanisms of viral co-infection. Declarations Ethics approval and consent to participate This study was reviewed and approved by the Ethics Committee of Shanghai Skin Disease Hospital: No. 2025-52 (Departmental), and ethical clearance was obtained from the same institution. Data collection was voluntary, with all participants choosing to participate freely. The study was designed to respect the dignity and autonomy of HPV-infected individuals. Oral information on study objectives and procedures was provided, and informed consent was obtained before questionnaire administration. This study strictly followed the principles of the Declaration of Helsinki. Consent for publication All authors consent to the publication of this study. Competing Interests The authors declare that they have no competing interests. Funding This study was supported by the Talent Introduction Special Fund of Shanghai Skin Disease Hospital (No. 2022KYQD03) and Key disciplines development Fund of Shanghai Skin Disease Hospital. Author Contribution Xiaoping Gu: Conceptualization, Formal analysis, and Writing-original draft. Yijie Tang: Methodology. Dandan Yang: Data curation and Formal analysis. Qinghui Xie: Methodology. , Lingling Fu: Data curation and Resources. Qingqiong Luo: Conceptualization and Funding acquisition. Acknowledgement Not applicable. Data Availability All the data in this article are included in the manuscript. References Singh D, Vignat J, Lorenzoni V, Eslahi M, Ginsburg O, Lauby-Secretan B, Arbyn M, Basu P, Bray F, Vaccarella S. Global estimates of incidence and mortality of cervical cancer in 2020: a baseline analysis of the WHO Global Cervical Cancer Elimination Initiative. Lancet Glob Health. 2023;11(2):e197–206. 10.1016/s2214-109x(22)00501-0 . Cao W, Chen HD, Yu YW, Li N, Chen WQ. Changing profiles of cancer burden worldwide and in China: a secondary analysis of the global cancer statistics 2020. Chin Med J (Engl). 2021;134(7):783–91. 10.1097/cm9.0000000000001474 . 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Monteiro JC, Fonseca RRS, Ferreira TCS, Rodrigues LLS, da Silva ARB, Gomes ST, Silvestre RVD, Silva A, Pamplona I, Vallinoto ACR, Ishak R, Machado LFA. Prevalence of High Risk HPV in HIV-Infected Women From Belém, Pará, Amazon Region of Brazil: A Cross-Sectional Study. Front Public Health. 2021;9:649152. 10.3389/fpubh.2021.649152 . Yao X, Li Q, Chen Y, Du Z, Huang Y, Zhou Y, Zhang J, Wang W, Zhang L, Xie J, Xu C, Ge Y, Zhou Y. Epidemiology of human papillomavirus infection in women from Xiamen, China, 2013 to 2023. Front Public Health. 2024;12:1332696. 10.3389/fpubh.2024.1332696 . Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviewers invited by journal 07 Apr, 2026 Editor assigned by journal 05 Mar, 2026 Editor invited by journal 04 Mar, 2026 Submission checks completed at journal 03 Mar, 2026 First submitted to journal 03 Mar, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8899569","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":621827301,"identity":"84ca0b24-46d6-4468-9843-95bb9e2cd5e3","order_by":0,"name":"Xiaoping Gu","email":"","orcid":"","institution":"Shanghai Skin Disease Hospital, School of Medicine, Tongji University","correspondingAuthor":false,"prefix":"","firstName":"Xiaoping","middleName":"","lastName":"Gu","suffix":""},{"id":621827302,"identity":"cc6100ff-3a3e-48ed-b58a-47aafef4595f","order_by":1,"name":"Yijie Tang","email":"","orcid":"","institution":"Shanghai Skin Disease Hospital, School of Medicine, Tongji University","correspondingAuthor":false,"prefix":"","firstName":"Yijie","middleName":"","lastName":"Tang","suffix":""},{"id":621827305,"identity":"ee127bd9-64f7-4dfe-bdb4-afb97f61a319","order_by":2,"name":"Dandan Yang","email":"","orcid":"","institution":"Shanghai Skin Disease Hospital, School of Medicine, Tongji University","correspondingAuthor":false,"prefix":"","firstName":"Dandan","middleName":"","lastName":"Yang","suffix":""},{"id":621827308,"identity":"53777e20-8d39-4621-b96d-4805fc3ec504","order_by":3,"name":"Qinghui Xie","email":"","orcid":"","institution":"Shanghai Skin Disease Hospital, School of Medicine, Tongji University","correspondingAuthor":false,"prefix":"","firstName":"Qinghui","middleName":"","lastName":"Xie","suffix":""},{"id":621827309,"identity":"be53132b-63fa-41de-8636-f997106c44d0","order_by":4,"name":"Lingling Fu","email":"","orcid":"","institution":"Shanghai Skin Disease Hospital, School of Medicine, Tongji University","correspondingAuthor":false,"prefix":"","firstName":"Lingling","middleName":"","lastName":"Fu","suffix":""},{"id":621827310,"identity":"a90abf18-8209-4dec-8860-43e9ae2edb04","order_by":5,"name":"Qingqiong Luo","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABBElEQVRIie3PMUsDMRTA8YRAukTrGId+h0ggdLhv4pLjIJPuHc56ILwualed/AqOjj0etMthV93ORRxPnAQHE1BxubSjYP6QEEJ+kEdIKvUH2w2b9YuHQ6fk6Zyxuo0R/pvQq0lGr2e8UBvJd0w0jt6uhdmLElnUD093J6PLwQW+7AAyjcQQUmaH/cQV47xZaRD3brwPyA0S15KlO656yZGROSxz8Ad1ACg8WSla4ZYkB5T6jILcgpSB6HbROKUY43Einv0ssPCzNIZWk8xK5EzZyCzDQVE/vsN0dDM7128fStrhfP3admXWS0KSEKRV+OTPlY08/yLTQFi34WEqlUr90z4B9nVaIjAcP8UAAAAASUVORK5CYII=","orcid":"","institution":"Shanghai Skin Disease Hospital, School of Medicine, Tongji University","correspondingAuthor":true,"prefix":"","firstName":"Qingqiong","middleName":"","lastName":"Luo","suffix":""}],"badges":[],"createdAt":"2026-02-17 09:25:22","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8899569/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8899569/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":107106570,"identity":"c7ac3457-2d63-42c7-b213-acebba287942","added_by":"auto","created_at":"2026-04-16 21:22:39","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":410603,"visible":true,"origin":"","legend":"\u003cp\u003eHPV subtypes infection rate.\u003c/p\u003e","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8899569/v1/99cc7b14d22daad113eec4c0.jpg"},{"id":107106571,"identity":"9c66badb-cb8e-4422-90de-09ffa7b3aad6","added_by":"auto","created_at":"2026-04-16 21:22:39","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":369766,"visible":true,"origin":"","legend":"\u003cp\u003eDifferent HPV subtypes mixed infection rate.\u003c/p\u003e","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8899569/v1/5b0caf6a04c9e10437ca24b5.jpg"},{"id":107481861,"identity":"08cbc9e8-15bd-4f2e-905a-2791642cf9b1","added_by":"auto","created_at":"2026-04-22 02:20:31","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":5713,"visible":true,"origin":"","legend":"\u003cp\u003eHPV infection rate in TCT.\u003c/p\u003e","description":"","filename":"placeholderimage.png","url":"https://assets-eu.researchsquare.com/files/rs-8899569/v1/0b4eb9ae9a081c242afc3611.png"},{"id":107705052,"identity":"682981d5-34d7-41e9-99a6-f0496a8a0330","added_by":"auto","created_at":"2026-04-24 09:07:12","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1089272,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8899569/v1/ef6471cd-5248-40ed-a7da-1d3003783843.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Epidemiological study of HPV infection in Shanghai: a population study based on screening for HPV infection","fulltext":[{"header":"Introduction","content":"\u003cp\u003eCervical cancer (CC) is a common gynecological cancer and a major cause of cancer-related deaths. Globally, in 2020, there were 604,127 CC cases registered, 341,831 leading to death. Age-standardized incidences are 13.3/100,000 women-years, and mortality rates are 7.2/100,000 women-years [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. In China, CC contributed an estimated 109,741 cases and 59,060 deaths in women according to a secondary analysis of the GLOBOCAN 2020 data [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Human papillomavirus (HPV) is the most common sexually transmitted pathogen worldwide, and its global incidence is increasing. Sexual intercourse is the main route of transmission. HPV infection can cause a variety of female genital tract diseases, such as anogenital warts, cervical intraepithelial neoplasia, and CC [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Research estimates that about 80% of sexually active women will contract HPV at some stage in their lives. More than 90% of individuals can clear the virus through their immune system. However, persistent HPV infection can lead to CC without timely treatment.\u003c/p\u003e \u003cp\u003eMore than 200 genotypes of HPV have been identified. HPV types can be classified into low-risk and high-risk strains depending on their oncogenic potential. Persistent infection with high-risk HPV is a key driver of cervical cancer, which remains a major contributor to global cancer-related morbidity and mortality in women [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Notably, HPV16 and HPV18 are the most prevalent high-risk-HPV types, responsible for 70% of CC. In contrast, low-risk HPV types mainly cause warts of the genitals, anus, mouth, throat, and oropharyngeal tumours [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Given the high prevalence of HPV and its heavy disease burden, understanding the epidemiological characteristics of HPV and their relationship with clinical manifestations is essential for targeted prevention and clinical management.\u003c/p\u003e \u003cp\u003eThe aim of this study was to clarify the status of HPV infection and HPV subtypes among women of different age groups in Shanghai. Our findings can be useful in developing effective measures and approaches to preventing infection with both high- and low-risk HPV subtypes. To better understand the prevalence of HPV infection among women in Shanghai, we collected and analyzed data of all age groups who underwent HPV testing at Shanghai Skin Disease Hospital in Shanghai.\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eSpecimen collection and preservation\u003c/h2\u003e \u003cp\u003eBefore collecting the sample, gently wipe off excessive secretions around the cervix using a cotton swab. Insert the cervical sampling brush into the junction of the squamous and columnar epithelium at the cervix opening, and rotate it clockwise or counterclockwise for 3\u0026ndash;5 turns to collect cervical exfoliated cells. Place the collected cells into a sampling tube labeled with the patient\u0026rsquo;s identification number and seal it tightly for submission. After specimen collection, it should be promptly tested. Specimens stored at a temperature of 2\u0026ndash;8℃ should be tested within 3 days, while specimens stored at -20℃ should be tested within 12 months. The specimen should be avoided from repeated freezing and thawing, with a maximum of 5 cycles. If using an ice pack for transportation, it should not exceed 3 days. This study has been reviewed and approved by the Ethics Committee of Shanghai Skin Disease Hospital, No. 2025-52 (Departmental).\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eHPV genotyping\u003c/h3\u003e\n\u003cp\u003eCervical samples were collected with a cytobrush for genomic DNA extraction. After vortexing, 350 \u0026micro;L of the sample was used with a nucleic acid extraction reagent, and HPV DNA was extracted via a nucleic acid extractor.1 \u0026micro;L DNA was mixed with 24 \u0026micro;L amplification reagent, centrifuged, and subjected to PCR: denaturation at 20℃ for 10 min, and 95℃ for 9 min. Followed by 40 cycles at 95℃ for 20 s, 55℃ for 30 s, and 72℃ for 30 s, and finally extension at 72℃ for 5 min. For PCR, block the membrane with blocking solution twice, then add enzyme-labeled solution at 25℃ for 3.5 min. After pumping out, set to 36℃, wash with Solution A four times, add chromogenic solution for 3\u0026ndash;5 min, pump out, wash with Solution B three times and distilled water, then remove the membrane and analyze results within an hour. During PCR product hybridization, preheat the hybridization solution to 45℃, prepare the instrument, denature the PCR product at 95℃, then ice-water bath, and perform hybridization at 45℃ with preheated solution, maintaining the temperature throughout.\u003c/p\u003e\n\u003ch3\u003eThinPrep cytologic test (TCT)\u003c/h3\u003e\n\u003cp\u003eSpecimens positive for HPV genotyping were directly used for TCT. Two experienced cytopathologists diagnosed the liquid cytology specimens independently.If their diagnoses differed, a third cell pathologist reviewed the sample. Cytological results were classified according to the Bethesda System. The classification included five categories: negative for intraepithelial lesion and malignancy (NILM), atypical squamous cells of undetermined significance (ASC-US), atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion (ASC-H), low-grade squamous intraepithelial lesion (LSIL), and high-grade squamous intraepithelial lesion (HSIL) [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eData were analysed using GraphPad Prism 9.0 software. The HPV positivity rate was expressed as a percentage. Count data was used to calculate the number of positive and negative cases for each type of HPV. A chi-square test was performed to determine if there were statistically significant differences between the two groups. The χ\u003csup\u003e2\u003c/sup\u003e test was applied to compare the infection rate of different age groups and the infection rate of HPV genotyping according to additional TCT classifications. Differences were considered statistically significant if the difference was \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003e \u003cb\u003eResult 1. Epidemiological Characteristics of HPV Infection.\u003c/b\u003e \u003c/p\u003e \u003cp\u003eThe prevalence of HPV infection was analyzed across different age groups and between males and females, as presented in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Among all 21,188 participants, the overall HPV infection rate was 55.09% (95% CI: 54.38\u0026ndash;55.80). Females exhibited a significantly higher HPV infection rate (65.31%, 95% CI: 64.21\u0026ndash;66.41) than males (52.52%, 95% CI: 51.80-53.24). Regarding age stratification, the HPV infection rates showed an upward trend with increasing age in both genders. For males, the infection rate was 53.15% (95% CI: 51.72\u0026ndash;54.58) in the \u0026le;\u0026thinsp;30 years group, 54.02% (95% CI: 52.78\u0026ndash;55.26) in the 31\u0026ndash;40 years group, 54.29% (95% CI: 52.63\u0026ndash;55.95) in the 41\u0026ndash;50 years group, 59.28% (95% CI: 56.38\u0026ndash;62.18) in the 51\u0026ndash;60 years group, and peaked at 55.02% (95% CI: 52.05\u0026ndash;57.99) in the \u0026ge;\u0026thinsp;60 years group.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eHPV infection at different Ages and Gender.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"11\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eAge group (years)\u003c/p\u003e \u003cp\u003eSex\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eTotal number of cases\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eNumber of infections\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c9\" namest=\"c6\"\u003e \u003cp\u003ePercentage (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eTotal (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c11\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e95% CI\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003e95% CI\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003e95% CI\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026le;\u0026thinsp;30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4395\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1604\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2336\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e910\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e53.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e51.72\u0026ndash;54.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e56.74\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e54.30-59.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e54.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e52.85\u0026ndash;55.31\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e31\u0026ndash;40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5335\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2739\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2882\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1509\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e54.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e52.78\u0026ndash;55.26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e55.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e53.44\u0026ndash;56.74\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e54.38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e53.35\u0026ndash;55.41\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e41\u0026ndash;50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3122\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1259\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1695\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e687\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e54.29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e52.63\u0026ndash;55.95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e54.57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e51.85\u0026ndash;57.29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e54.37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e52.98\u0026ndash;55.76\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e51\u0026ndash;60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1083\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e473\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e642\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e288\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e59.28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e56.38\u0026ndash;62.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e60.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e56.63\u0026ndash;65.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e59.77\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e57.12\u0026ndash;62.42\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1036\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e422\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e570\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e339\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e55.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e52.05\u0026ndash;57.99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e80.33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e76.61\u0026ndash;84.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e59.98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e56.94\u0026ndash;63.02\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e15472\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5716\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e8125\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3733\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e52.52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e51.80-53.24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e65.31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e64.21\u0026ndash;66.41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e55.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e54.38\u0026ndash;55.80\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eFor females, the infection rate increased markedly with age, ranging from 56.74% (95% CI: 54.30-59.18) in the \u0026le;\u0026thinsp;30 years group to 80.33% (95% CI: 76.61\u0026ndash;84.05) in the \u0026ge;\u0026thinsp;60 years group, which was the highest infection rate across all subgroups. The total HPV infection rate in each age group was 54.08% (\u0026le;\u0026thinsp;30 years), 54.38% (31\u0026ndash;40 years), 54.37% (41\u0026ndash;50 years), 59.77% (51\u0026ndash;60 years), and 59.98% (\u0026ge;\u0026thinsp;60 years), respectively, with a gradual elevation as age advanced.\u003c/p\u003e \u003cp\u003e \u003cb\u003eResult 2. Age Distribution of High and Low Risk HPV Subtypes.\u003c/b\u003e \u003c/p\u003e \u003cp\u003eHPV06 exhibited the highest prevalence, with an infection rate of 9.515%, demonstrating a substantial predominance over all other detected subtypes. Other relatively prevalent genotypes comprised HPV71, HPV31, HPV45, HPV16, and HPV68, as illustrated in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Within high-risk HPV genotypes, the top five most prevalent types were HPV31, HPV45, HPV16, HPV68, and HPV58, indicating a potential correlation between these specific subtypes and CC among patients in the Shanghai region.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe distribution and mixed-infection status of the top 10 high-risk and low-risk HPV subtypes are presented in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Of all listed subtypes, HPV06, a low-risk genotype, had the largest number of total positive samples (2016) and the highest mixed-infection rate (34.40%). HPV71 and HPV31 were the second and third most prevalent, with mixed-infection rates of 32.19% and 30.85%, respectively. Among the top 10 HPV subtypes, six were high-risk genotypes, namely HPV31, HPV45, HPV16, HPV68, HPV58, and HPV52, whose mixed-infection rates ranged from 25.41% to 29.72%. The remaining four subtypes were low-risk, including HPV06, HPV71, HPV43, and HPV42, with mixed-infection rates between 26.20% and 34.40%. Overall, low-risk HPV subtypes tended to exhibit higher mixed-infection rates compared with high-risk subtypes in this study.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eThe high-risk of HPV subtype mixed-infection\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRank\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHPV Subtype\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRisk Category\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTotal Positive Samples\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eMixed-infection Samples\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHPV06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLow-risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2016\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e34.40%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHPV71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLow-risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1187\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e32.19%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHPV31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eHigh-risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1167\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e30.85%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHPV45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eHigh-risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1090\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e29.72%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHPV16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eHigh-risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1012\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e28.65%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHPV68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eHigh-risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e977\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e27.94%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHPV58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eHigh-risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e922\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e26.89%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHPV43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLow-risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e905\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e26.52%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHPV42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLow-risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e897\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e26.20%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHPV52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eHigh-risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e862\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e25.41%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eResult 3. Severity Distribution of HPV Mixed Infections.\u003c/b\u003e \u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e illustrates the profile of HPV mixed infection according to the number of concurrent subtypes. Among the 5,862 identified mixed infection cases, dual-subtype infection represented the dominant form, with a proportion of 55.35%. The proportion of cases gradually decreased as the number of infected subtypes increased: 28.81% for 3 subtypes, 11.14% for 4 subtypes, 3.43% for 5 subtypes, and only 1.28% for 6 or more subtypes. The mean number of coinfected subtypes across all mixed infection cases was 2.6, and the average number of infected subtypes in the 6 or more subtypes group was 6.8.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eThe status of HPV subtype mixed-infection\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of Subtypes in Mixed Infection\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNumber of Cases\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePercentage of Mixed Infections (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAverage Number of Infected Subtypes\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2 Subtypes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3245\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e55.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3 Subtypes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1689\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28.81\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4 Subtypes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e653\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5 Subtypes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e201\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6\u0026thinsp;+\u0026thinsp;Subtypes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.8 (Average)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5862\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eTo better investigate which HPV subtype is more prone to mixed infection, we conducted a further analysis of mixed infection status. The results showed that all mixed infection cases, HPV06 was the most frequently involved subtype, accounting for 13% of the total mixed-infection count, which was higher than any other genotype (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The next common subtypes included HPV71 and HPV31, each accounting for 7%, followed by HPV45 and HPV16 with 6% respectively. In addition, HPV58, HPV43, HPV42 each accounted for 5%, while HPV70, HPV26, HPV44 accounted for 3% individually. The remaining subtypes such as HPV66, HPV59, HPV56, HPV55, HPV33, HPV11, HPV53 and HPV52 each constituted 4% of the mixed infections.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eResult 4. HPV Mixed Infection Prevalence, Subtype Distribution and High-Risk Co-Infection Tendencies\u003c/h2\u003e \u003cp\u003eTo evaluate the association between pathological results and HPV infection profiles, we analyzed the HPV infection rates and mixed infection patterns across different cervical lesion categories. As presented in Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e, distinct differences were observed in HPV infection characteristics among various lesion types. LSIL, the HPV infection rate reached 90.63% (29/32 cases), with 58.62% of HPV-positive cases exhibiting mixed infections. In the ASC-H subgroup, the HPV infection rate was even higher at 94.12% (16/17 cases), and 68.75% of these positive cases had mixed infections, indicating the highest viral complexity among all groups. In the ASC-US cohort, the HPV infection rate was 77.55% (38/49 cases), with 55.26% of positive cases showing mixed infections. Notably, among the NILM group, despite the absence of significant pathological changes, the HPV infection rate still reached 65.20% (669/1026 cases), and 37.07% of these positive cases had mixed infections. These findings collectively demonstrate a positive correlation between the severity of cervical lesions and HPV infection rates, as well as the proportion of mixed infections. The high HPV infection rates and mixed infection ratios in LSIL and ASC-H groups suggest a strong association between persistent or complex HPV infections and the progression of cervical lesions. Even in the NILM group, the considerable HPV infection rate highlights the latent risk of future lesion development, emphasizing the importance of continuous HPV surveillance in this population.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eThe relationship between high-risk genotypes and TCT results in HPV-positive specimens\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLesion Type\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNumber of Cases\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eHPV Infection Cases\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHPV Infection Rate (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eMixed Infection Ratio (Among Positive Cases)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLSIL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e90.63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e58.62\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eASC-H\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e94.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e68.75\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eASC-US\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e77.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e55.26\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNILM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1026\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e669\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e65.20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e37.07\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eTo illustrate the distribution of high-risk HPV genotypes across different cervical lesion groups, we analyzed the infection rates of six prominent subtypes (HPV16, HPV18, HPV31, HPV45, HPV58, and HPV68) in LSIL, ASC-H, ASC-US, and NILM populations, as presented in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. For HPV16, the highest infection rate was observed in ASC-H (56.00%), followed by LSIL (38.00%), ASC-US (32.00%), and NILM (10.00%). HPV18 showed the strongest association with ASC-H (32.00%), while its infection rates in LSIL (21.00%), ASC-US (14.00%), and NILM (3.00%) were relatively lower. HPV31 exhibited a high infection rate in ASC-H (44.00%), followed by LSIL (31.00%), ASC-US (27.00%), and NILM (12.00%). For HPV45, ASC-H (26.00%) and ASC-US (22.00%) had comparable infection rates, with LSIL (18.00%) and NILM (10.00%) showing lower rates. HPV58 was most prevalent in ASC-H (38.00%), followed by LSIL (28.00%), ASC-US (24.00%), and NILM (9.00%). Similarly, HPV68 had the highest infection rate in ASC-H (26.00%), with LSIL (25.00%), ASC-US (19.00%), and NILM (9.00%) showing decreasing trends. Collectively, these data demonstrate that high-risk HPV subtypes, particularly HPV16, HPV31, and HPV58, have a strong association with ASC-H and LSIL, indicating their potential role in driving cervical lesion progression. Even in NILM, the detectable infection rates of these subtypes highlight the latent risk of future pathological changes, underscoring the importance of targeted surveillance for these high-risk genotypes across all lesion categories.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn China, the low vaccination rate has resulted in a persistently high prevalence of HPV infection [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. The prevalence and genotypic distribution of HPV vary with living environment, social behavior, and other factors [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Understanding the profile of HPV infection in Shanghai is crucial for the development of targeted strategies for the prevention and control of CC [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe present study provides a comprehensive characterization of HPV epidemiology in a large cohort of 21,188 individuals, encompassing age and gender-specific distribution, subtype prevalence, infection patterns, and associations with cervical epithelial abnormalities. These findings offer critical insights into HPV transmission dynamics, disease burden, and implications for clinical management and public health strategies. The infection rate in males showed little correlation with age, with an overall infection rate of 52.52%. This infection rate was much higher than that in the population study of Xuhui District, Shanghai, which may be attributed to the fact that the sample-collecting hospital is a dermatological hospital with a more concentrated patient population[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. The infection rate in females increased continuously with age, and when females were \u0026ge;\u0026thinsp;60 years old, the overall infection rate reached as high as 80.33%. Notably, the \u0026ge;\u0026thinsp;60 years group exhibited a significantly higher infection rate than the 41\u0026ndash;50 years group, emphasizing the need for continued HPV screening in postmenopausal women, who are often overlooked in current guidelines despite their elevated risk of persistent infections. High infection rates in younger adults reflect increased sexual activity and recent HPV acquisition, while the rebound in older age groups is attributed to immune senescence, reactivation of latent infections, or new sexual exposures.\u003c/p\u003e \u003cp\u003eAmong the infected population, mixed infections accounted for 55.35%, indicating that half of the patients were infected with two or more HPV subtypes. The most common subtypes were HPV06, HPV71, HPV31, HPV45, and HPV16. The top two infected subtypes were both low-risk genotypes, and these two subtypes were common in mixed infections, while HPV31, HPV45, and HPV16 were high-risk subtypes. This is slightly different from the subtypes in other regions, where high-risk subtypes such as HPV16, HPV52, and HPV58 are often the most common infected subtypes [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. This may be due to the fact that the hospital mainly treats patients with skin diseases, while low-risk HPV subtypes are mainly associated with skin lesions.\u003c/p\u003e \u003cp\u003eThis large-scale HPV screening study focused on women in the region, with findings closely tied to the uniqueness of the research population. Notably, the overall HPV infection rate among the regular screening cohort was higher than the data from general outpatient clinics of some comprehensive hospitals [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. This discrepancy may be attributed to the sample source, as the positivity rate among women attending gynecological clinics is generally higher than that among those undergoing routine health check-ups [\u003cspan additionalcitationids=\"CR20\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eWe noticed that the infection rate among males showed little variation across all age groups and was much higher than the data reported in other studies, all exceeding 50%. HPV infection in males was often accompanied by infections with other pathogens, accounting for approximately 74.4% [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]。In others research, HPV DNA was detected in 19.4% (6/31) of the semen samples [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. HPV16 DNA was detected in peripheral blood leukocytes of individuals with HPV-positive seminal samples, indicating that HPV infection may not be confined solely to the lesion sites in males [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Studies have shown that the infertility rate in men with HPV DNA-positive semen is four times higher than that in HPV DNA-negative men [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. This finding may be associated with the increasing incidence of infertility in China.\u003c/p\u003e \u003cp\u003eThe distribution of HPV genotypes in the present cohort exhibited distinct subtype-specific patterns that align with global epidemiological trends while reflecting regional characteristics[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. High-risk HPV subtypes, especially HPV16, 31, 45, and 58, were predominant in younger males. Among men aged 31\u0026ndash;40 years, HPV16 was the most common subtype, consistent with its role as the leading oncogenic type worldwide, which is responsible for approximately 50% of CC cases. Notably, HPV58, a subtype highly prevalent in East Asian populations, showed substantial infection rates in both LSIL (28.00%) and ASC-H (38.00%), emphasizing its region-specific carcinogenic potential that warrants increased attention in vaccination and screening strategies.\u003c/p\u003e \u003cp\u003eThe high frequency of mixed HPV infections is consistent with recent reports and carries significant clinical implications [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Co-infections with 2\u0026ndash;3 HPV subtypes were predominant, indicating frequent interactions among HPV types within the genital tract that may affect viral persistence, oncogenic potential, and treatment response. High coinfection rates of oncogenic subtypes with other high-risk subtypes may confer additive or synergistic carcinogenic effects, as exemplified by HPV18 mixed-infection with HPV16 or HPV31, which contributes to the aggressive behavior of cervical adenocarcinomas. The strong correlation between cervical lesion severity and HPV infection rates, particularly mixed infections, further supports the causal role of HPV in cervical carcinogenesis. Nearly universal HPV positivity in ASC-H (94.12%) and high mixed infection rates in LSIL (58.62%) and ASC-US (55.26%) underscore the importance of HPV testing in triaging abnormal cytology. Detection of high-risk subtypes in NILM women highlights latent lesion risk and supports extended follow-up. The predominance of specific subtypes in precancerous lesions informs risk-stratified management, with aggressive intervention for high-risk combinations and observation for low-risk infections.\u003c/p\u003e \u003cp\u003eIn conclusion, this large-scale study provides a contemporary epidemiological profile of HPV infection, highlighting age- and gender-specific patterns, subtype distribution, and mixed infection dynamics. These findings highlight the necessity of personalized screening and vaccination strategies. They prioritize younger males for the prevention of high-risk HPV-related malignancies and older females for cervical cancer prevention.These results also emphasize the complexity of HPV-associated diseases and support further research into the mechanisms of viral co-infection.\u003c/p\u003e"},{"header":"Declarations","content":" \u003cp\u003e \u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e \u003cp\u003eThis study was reviewed and approved by the Ethics Committee of Shanghai Skin Disease Hospital: No. 2025-52 (Departmental), and ethical clearance was obtained from the same institution. Data collection was voluntary, with all participants choosing to participate freely. The study was designed to respect the dignity and autonomy of HPV-infected individuals. Oral information on study objectives and procedures was provided, and informed consent was obtained before questionnaire administration. This study strictly followed the principles of the Declaration of Helsinki.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eConsent for publication\u003c/strong\u003e \u003cp\u003e All authors consent to the publication of this study.\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eCompeting Interests\u003c/h2\u003e \u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eThis study was supported by the Talent Introduction Special Fund of Shanghai Skin Disease Hospital (No. 2022KYQD03) and Key disciplines development Fund of Shanghai Skin Disease Hospital.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eXiaoping Gu: Conceptualization, Formal analysis, and Writing-original draft. Yijie Tang: Methodology. Dandan Yang: Data curation and Formal analysis. Qinghui Xie: Methodology. , Lingling Fu: Data curation and Resources. Qingqiong Luo: Conceptualization and Funding acquisition.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e \u003cp\u003eNot applicable.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eAll the data in this article are included in the manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eSingh D, Vignat J, Lorenzoni V, Eslahi M, Ginsburg O, Lauby-Secretan B, Arbyn M, Basu P, Bray F, Vaccarella S. Global estimates of incidence and mortality of cervical cancer in 2020: a baseline analysis of the WHO Global Cervical Cancer Elimination Initiative. 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Front Public Health. 2024;12:1332696. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3389/fpubh.2024.1332696\u003c/span\u003e\u003cspan address=\"10.3389/fpubh.2024.1332696\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"infd","sideBox":"Learn more about [BMC Infectious Diseases](http://bmcinfectdis.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/infd","title":"BMC Infectious Diseases","twitterHandle":"#bmcinfectdis","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Human papillomavirus, Subtype distribution, Mixed infection, Cervical lesions","lastPublishedDoi":"10.21203/rs.3.rs-8899569/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8899569/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eHuman papillomavirus (HPV) infection is the primary cause of cervical cancer (CC). Although the HPV vaccination rate has been increasing, the HPV infection rate remains persistently high. Therefore, understanding the epidemiological patterns of HPV is crucial for controlling its infection and transmission. To investigate the HPV epidemiological characteristics and its association with cervical epithelial abnormalities, 21,188 individuals who underwent HPV testing between September 2023 and September 2025 were enrolled. The overall HPV positivity rate was 55.09%, with a higher infection rate in females than in males, and the infection rate increased with age. HPV infections often occurred in the form of mixed infections, which accounted for 50.91% of all positive samples, mainly involving 2 to 3 subtypes. Among the top five most prevalent HPV subtypes, HPV06 and HPV31, both low-risk genotypes, were the most common single infection types and also the most frequently involved in mixed infections. HPV31, HPV45, and HPV16 were the most common high-risk subtypes, and their infections tended to present as mixed infections. HPV infection and mixed infection rates were positively correlated with lesion severity: 94.12% (68.75% mixed) in ASC-H, 90.63% (58.62% mixed) in LSIL, 77.55% (55.26% mixed) in ASC-US, and 65.20% (37.07% mixed) in NILM. HPV16/18 exhibited a strong association with high-grade lesions. These results confirm age- and gender-specific HPV distribution patterns, emphasizing the role of high-risk subtypes and mixed infections in lesion progression, and support the need for tailored screening, vaccination, and risk-stratified management.\u003c/p\u003e","manuscriptTitle":"Epidemiological study of HPV infection in Shanghai: a population study based on screening for HPV infection","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-16 21:22:35","doi":"10.21203/rs.3.rs-8899569/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewersInvited","content":"","date":"2026-04-07T22:43:47+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-03-05T13:56:54+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-03-04T07:42:48+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-03-04T04:30:22+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Infectious Diseases","date":"2026-03-04T04:23:56+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"infd","sideBox":"Learn more about [BMC Infectious Diseases](http://bmcinfectdis.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/infd","title":"BMC Infectious Diseases","twitterHandle":"#bmcinfectdis","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"c492da01-7ba2-4f66-b15d-3d43e5926222","owner":[],"postedDate":"April 16th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-04-16T21:22:35+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-16 21:22:35","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8899569","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8899569","identity":"rs-8899569","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}