- Research
- Open access
- Published:
HPV specificity and multiple infections and association with cervical cytology in Chongqing, China: a cross-sectional study
BMC Infectious Diseases volume 24, Article number: 804 (2024)
Abstract
Background
It is important to assess the relationship between specific HPV genotype or multiple infection and cervical cytology. The protection provided by the HPV vaccine is type-specific, and the epidemiology feature of coinfections needs to be investigated. The aim is to provide baseline information for developing HPV vaccination and management of HPV-positive populations in the region.
Methods
A total of 3649 HPV-positive women were collected from 25,572 women who underwent 15 HR-HPV genotypes and ThinPrep cytologic test (TCT) results. Logistic regression was used to determine the correlation between the risk of cytology abnormalities and specific HPV infection. We calculated odds ratios (ORs) to assess coinfection patterns for the common two-type HPV infections. chi-squared test was used to estimate the relationship between single or multiple HPV (divided into species groups) infection and cytology results.
Results
The results showed there was a positive correlation between HPV16 (OR = 4.742; 95% CI 3.063–7.342) and HPV33 (OR = 4.361; 95% CI 2.307–8.243) infection and HSIL positive. There was a positive correlation between HPV66 (OR = 2.445; 95% CI 1.579–3.787), HPV51 (OR = 1.651; 95% CI 1.086–2.510) and HPV58(OR = 1.661; 95% CI 1.166–2.366) infection and LSIL. Multiple HPV infections with α9 species (OR = 1.995; 95% CI 1.101–3.616) were associated with a higher risk of high-grade intraepithelial lesions (HSIL) compared with single HPV infection. There were positive correlations between HPV66 and HPV56 (α6) (OR = 3.321; 95% CI 2.329–4.735) and HPV39 and HPV68 (α7). (OR = 1.677; 95% CI 1.127–2.495). There were negative correlations between HPV52, 58, 16 and the other HPV gene subtypes.
Conclusion
HPV33 may be equally managed with HPV16. The management of multiple infections with α9 may be strengthened. The 9-valent vaccine may provide better protection for the population in Chongqing currently. The development of future vaccines against HPV51 and HPV66 may be considered in this region.
Introduction
Cervical cancer is the fourth most common cancer amongst women in the world, with approximately 604,000 new cases and 342,000 deaths in 2020 [1]. Persistent high-risk human papilloma virus (HR-HPV) infection is a key risk factor leading to precancerous intraepithelial lesions [2]. At present, more than 200 HPV genotypes have been identified, among which HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68 are high-risk carcinogenic types [3]. Most of the carcinogenic or HR-HPV genotypes are α-papilloma virus [3].α9 clade (including HPV16, 58, 33, etc.) is the most important species, which was more likely to result in serious cervical lesions [4]. α7 is mainly associated with high-risk mucosal lesions, including HPV18, 45, 39, etc., and the others include α5 (HPV51, 82), α6 (HPV56, 66) etc. [5]. Trottier et al. [6] found that multiple HPV infections are associated with the highest risk of invasive cervical cancer compared with single infection, especially coinfection with α9 [7].
HPV16 and HPV18 are associated with 70% of cervical cancer [8]. However, other high-risk genotypes can also lead to cervical intraepithelial neoplasia and cervical cancer except HPV16/18 [3]. The influence of the different HPV genotypes on the development of cervical neoplasia remains and need further research [9].So it is necessary for optimizing specific genotype-based screening strategy and management of risk stratification due to the risk difference of different genotypes and multiple infection.
The WHO strategy for cervical cancer elimination: vaccination against HPV and early detection and treatment of cervical cancer [10]. In England, cervical cancer in women born since Sept 1, 1995 had been almost eliminated because of the HPV immunization programme [11]. So the HPV vaccine is the most efficient and critical prophylactic strategy in cervical cancer related to HPV genotypes. The prevalence of HPV infection and genotype distribution vary between countries and regions [12,13,14]. Meanwhile, it is essential to acquire information about HPV type-specific pathogenicity for cervical cancer. After all, the ultimate goal of HPV vaccination is to prevent cervical cancer.
Interactions between HPV types may have an impact on the overall effectiveness of an HPV vaccination program [15]. Okoye JO et al. [16] also pointed out there are some limitations in the efficacy of vaccines available to prevent cervical cancer because of multiple HPV infection. Therefore, the investigation of multiple infections is also very critical for the development of new multivalent vaccines.
Currently, there are five vaccines available in China: three imported vaccines (bivalent 2vHPV (Cervarix®, GSK), quadrivalent 4vHPV(Gardasil®, MSD) and 9-valent(Gardasil® 9, MSD), domestically produced bivalent vaccine (Cecolin®) and (Walrinax®). HPV vaccination is not included in the national immunization program in China. The majority of provinces require payment for HPV vaccination. The primary target group aged 9–14 years is less than 5% in China, which is far from the WHO 2030 targets [17]. Moreover, the HPV vaccine uptake was lower in the western regions corresponding to the eastern regions [18] which may due to lower-income and the more decrease socioeconomic status. Chongqing is one of the cities in Western China. Therefore, it is urgent to strengthen Chongqing's vaccine policy and develop new suitable vaccines suitable for Chongqing.
Our study analyzed the correlations between the specific HPV genotype and different cytological abnormality, evaluate the effects of multiple infections on cervical cytology compared to single infection, further analysis the co-infection pattern of several common HPV genotypes, provide a theoretical management of risk stratification for HPV-positive women and the choice of appropriate HPV vaccines and development.
Materials and Methods
Study population
This study is a cross-sectional, single-center study based on data from women who had HPV and TCT tests at the Health Examination and Oncology Screening Center in Chongqing University Cancer Hospital between January 1, 2016 to April 30, 2023. Subjects were women between the ages of 18 and 87 years old who actively taking part in cervical cancer screening. A total of 25,572 females who were screened for HR-HPV were enrolled. Eligible women were included who had a history of sexual activity, were not pregnant, and had no history of cervical cancer, had no severe immunodeficiency disease or other malignancies. 3649 HR-HPV-positive females were retrospectively analyzed. All participants were performed with the informed consent of the enrolled women. The study was approved by the Ethics Committee of Chongqing University Cancer Hospital (No. CZLS2023149-A).
Specimen collection and HPV genotyping
Cervical cellular samples were collected by a gynecologist with a specialized cervical brush. Specimens were stored at cell storaging solution by Yuanjiang Medical Supplies Co., Ltd. (Ningbo, China). The 15 HR-HPV types (HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68, and 82) was performed according to the manufacturer's instructions with the HPV Genotyping Kit by China Shanghai ZJ Bio-Tech Co., Ltd. HPV-positive was identified using PCR. The kits used 15 types of HPV specific primers and fluorescent probes according to the basic of TaqMan fluorescent probe-based quantitative real-time PCR. Run the following program: 94℃*2 min, 93℃*10 s, 62℃*31 s, for 40 cycles. The reaction temperature of the single point fluorescence was 62℃. The PCR was implemented in a 40 μl reaction mixture.
Thinprep cytologic test
Cervical cytological Classifications were performed in conformity with the Bethesda system. The results were analyzed independently by two experienced pathologists, including negative intraepithelial lesions or malignancy (NILM), atypical squamous cell of undetermined significance (ASC-US), low-grade squamous intraepithelial lesion (LSIL), and high-grade squamous intraepithelial lesion (HSIL), atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H) (Due to the small number of cases, it will be incorporated into high-grade lesions), atypical glandular cells (AGC) (There were few cases and no correlation analysis was performed).HSIL in this study included HSIL and ASC-H in this study.
Statistical analysis
SPSS 26.0 was used for statistical analysis. Graphpadprism9 software was used for graph drawing. The comparison between groups (single and multiple) was analyzed by chi-square test. Logistic regression was used to assess the correlation between HPV subtypes and cervical cytology. P < 0.05 indicates that subtypes of HPV infection may be association with cervical cytology abnormalities (HSIL, LSIL, ASC-US). With these positive results of ASC-US, LSIL, and HSIL as the dependent variable (yes = 1, no = 0) and HPV infection as the independent variable, a logistic regression model was established after adjusting for age. Those relationships (positively associated (OR > 1): more likely to occur together and negatively associated (OR < 1): less likely to occur together) between those common 2 genotypes were analyzed by Logistic regression. Odds ratios (ORs) and 95% confidence intervals (CIs) are presented. Taking HPV16, 52 and 58 infections as the dependent variable (yes = 1, no = 0) and the other several common HPV subtypes as the independent variable, the logistic regression model was established after adjusting for age.
Results
There were 715 multiple infections (563 cases were two HR‐HPV infections, 152 cases were triple or more HR‐HPV infections) among 3649 HR-HPV-positive females. Among all 15 HR-HPV genotypes, HPV52 (4.90%) was the most prevalent genotype, followed by HPV58(2.29%), HPV16(1.93%), HPV51(1.39%), HPV39(1.25%), HPV56(1.02%), HPV66(0.09%) among total HPV infections. Here was the prevalence of the main multiple HPV infections: HPV52(1.30%), HPV58(0.77%), HPV16 (0.63%), HPV51(0.54%), HPV56(0.50%), HPV39(0.46%), HPV66(0.43%) Fig. 1.
The logistic regression between the HPV subtype and ASC-US, LSIL, and HSIL are shown in above Tables 1,2 and 3. The logistic regression model was established after adjusting for age.
The results showed that there was a significant correlation between HPV68, HPV52 infection and ASC-US (P < 0.05) (Table 1). There was a positive correlation between HPV68 (OR = 1.856; 95% CI 1.206–2.855) and HPV52 (OR = 1.496; 95% CI 1.152–1.944) infection and ASC-US (Fig. 2a).
The logistic regression results of HPV subtype infection and LSIL are shown. The results showed that there was a significant correlation between HPV66, HPV51 and HPV58 infection and LSIL (P < 0.05) (Table 2). The results showed there was a significant positive correlation between HPV66 (OR = 2.445; 95% CI 1.579–3.787), HPV51 (OR = 1.651; 95% CI 1.086–2.510) and HPV58 (OR = 1.661; 95% CI 1.166–2.366) and LSIL. (Fig. 2b).
The logistic regression results of HPV subtype infection and HSIL are shown. The results showed that there was a correlation between HPV16, HPV33 and HPV39 infection and HSIL, and this difference reached statistical significance (P < 0.05) (Table 3). The results showed there was a significant positive correlation between HPV16(OR = 4.742; 95% CI 3.063–7.342) and HPV33 (OR = 4.361; 95% CI 2.307–8.243) infection and HSIL. There was a significant negative correlation between HPV39 (OR = 0.238; 95% CI 0.058–0.972) infection and HSIL (Fig. 2c).
Multiple HPV infections had an increased risk of LSIL (OR = 1.959; 95% CI 1.417–2.708) and HSIL (OR = 1.979; 95% CI 1.253–3.127) and it is statistically significant (LSIL: P < 0.001, HSIL: P < 0.01). The multiple HPV infections with clade α9 (more than 1 type belonging to clade α9) significant increased HSIL risk (OR = 1.995; 95% CI 1.101–3.616; P < 0.05). Women with multiple infections with clade α7, α6, and α5 are not at significant increased risk of HSIL compared to single infections. There were no differences for ASC-US and LSIL between multiple infections with clade α9, α7, α6, α5 and single infections (P > 0.05). The proportion of NILM with a single infection of α9 and α7 was significantly higher than that with multiple infections, and the differences were statistically significant (P < 0.05). There was no significant difference in α6 (P > 0.05) (Table 4).
Taking HPV16, 52 and 58 infections as the dependent variable (yes = 1, no = 0) and the other several common HPV subtypes as the independent variable, the logistic regression model was established after adjusting for age. The results showed that HPV52, HPV58, HPV51, HPV39, HPV56, HPV66, HPV68, HPV18 infection and HPV16 infection were negatively correlated (All OR < 1). There were negative correlations between HPV58, HPV51, HPV39, HPV56, HPV66, HPV68, HPV18 infection and HPV52 infection (All OR < 1). There were negative correlations between HPV51, HPV39, HPV56, HPV66, HPV68, HPV18 infection and HPV58 infection (All OR < 1). As co-infection with HPV66 and HPV56, HPV39 and HPV68 were common, we further analyzed the association. There were positive correlations between HPV66 and HPV56 (OR, 3.321, 95% CI 2.329–4.735), HPV39 and HPV68 (OR, 1.677, 95% CI 1.127–2.495) (Fig. 2d).
Discussion
Obtaining special epidemiological data about HPV infections was very important for cervical cancer prevention through HPV DNA testing and vaccination with regional-specific HPV preventive vaccines. In this study, the most popular genotypes were HPV52, HPV58 and HPV16, which was not consistent with other counties and other parts of our country [19, 20]. The distribution of HPV genotypes varies with geographic location and ethnic groups [21].
The correlation between specific HPV and cervical cell abnormalities may get guidance for preventative strategies and HPV vaccination programs. In our study, the logistic regression analysis was performed to determine whether there was a correlation between the occurrence of different cytological results and specific HPV subtypes. We found that HPV16 and HPV33 were positively correlated with HSIL. Luo Q et al. [10] Pointed out that HPV16 and HPV33 may be the most oncogenic genotypes. According to the principle of "equal risk equal management" [22], HPV33 may be equally managed with HPV16. Women infected by HPV33 might be early referral to colposcopy [23]. In addition, there was a positive correlation between HPV66, HPV51 and HPV58 infection and LSIL. In United State, HPV58 were associated with a relatively higher risk of cervical lesions in addition to HPV16, HPV18 and HPV33 [24]. The study found HPV58 was the most carcinogenic subtype except HPV16 [25]. In our study HPV66 was also commonly seen in multiple infections and was positively correlated with LSIL lesions. The research found that HPV66 had the higher prevalence in premalignant lesions [26]. HPV51 may play the contributory role to cervical cancer. The prevalence of HPV51 was higher in cervical lesions not only in Chongqing, but also in the other areas [27]. More attention should be paid to HPV 51 infection in the post-vaccine era in the area. Therefore, it seems that these three HPV infections (HPV66, HPV51 and HPV58) may also need to be managed intensively. There was a positive correlation between HPV68 and HPV52 infection and ASC-US (OR > 1). Although HPV52 was the most prevalent type in Chongqing, it was not associated with HSIL and LSIL in this study.
Besides specific HPV genotypes, multiple infection may be one of the high-risk factors for cervical cancer [28]. We also found that multiple HPV infection was associated with an increased risk of LSIL and HSIL compared with single infection, which was in line with the study [29]. In this study, the effects of multiple infection and single infection on cervical lesions in different HPV populations (including α9, α5, α6, α7) were further investigated, and it was found that coinfection with multiple a9 species was associated with an increased risk of HSIL. Previous studies have found that co-infection with α9 increases the risk of cervical disease [30, 31]. Other studies have indicated that multiple α7 subtype infections have an increased risk of cervical cancer [32]. In our study, multiple subtype infections with the α7 clade were found to be more likely to develop LSIL, but did not increase the risk of HSIL. Although multiple infections increase the risk of HSIL, it is likely to be largely due to multiple infections with α9 (HPV co-infection with α9 was the most). Therefore, the management of multiple infections with α9 may be strengthened.
In this study, we further investigated the association between the most common multiple HR-HPV. We found HPV66 and HPV56 (α6), HPV39 and HPV68 (α7) had the positive relationship, which is consistent with the relevant study in the United States [33]. This may be related to conserved amino acid sequences or structural similarity of shared neutralizing epitopes [34]. However, It was found negative interactions between the common α9 (HPV16, 52, and58) and other HPV subtypes (HPV51、HPV39、HPV56、HPV66、HPV68、HPV18) in this study. Dickson EL [35] also found that α9 appeared to be the only species with a strong negative association.
To a large extent, the protection provided by the HPV vaccine is type-specific. There may be more efficiency on the 9-valent vaccine against cervical lesions (against the top three prevalent HPV52, 58, and 16 as well as the more carcinogenic HPV 33, although its prevalence was not high) in Chongqing. Therefore, the 9-valent vaccine may provide better protection for the population of the vaccines currently available in Chongqing. But there is some challenge such as high-cost and insufficient vaccine supply about the 9-valent vaccine. Moreover the 9-valent HPV vaccine does not contain approximately 10% of HPV genotypes associated with high-grade lesions [36]. Our study found that the 9-valent HPV does not encompass the other HPV genotypes which lead to abnormal cytology in Chongqing. Therefore, it is necessary to develop new HPV vaccines to deal with related problems in China. Some HPV vaccines [37] (qvHPV vaccine, several 9vHPV vaccines, an 11vHPV vaccine, and a 14vHPV vaccine) are under development in China, and the successful marketing of locally developed HPV vaccines may help solve the supply problem and improve the vaccination rate. Considering the higher prevalence and pathogenicity of HPV51 and HPV66, the development of vaccines against HPV51 and HPV66 may be intensified in this region.
In the long term, high HPV vaccination coverage may affect the distribution of HPV infection types and the risk of type replacement may increase if HPV vaccination fails to induce strong cross-protection [38]. In this study, HPV16, HPV52, and HPV58 were negative associated with other common high-risk genotypes, which may increase the possibility of type substitution after HPV16 vaccination. A German study [39] found a decrease in HPV16, 18, and 31 infection rates and an increase in non-vaccine HPV infections such as HPV51, 53, 56, and 66. The cross-protection might associate with the phylogenetic distance from vaccine types [40]. From the perspective of vaccine substitution, the local vaccines in Chongqing also seemed to include HPV51 and HPV66. The other researches also recommended that HPV66 or HPV51 should be included in future HPV vaccine formulations [41,42,43].
This study was a single-center study. The data was based on a relatively small sample size. The multicenter and prospective studies in different geographic regions are still needed to be conducted to assure the results in the future.
Availability of data and materials
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
References
Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71(3):209–49.
Hillemanns P, Soergel P, Hertel H, Jentschke M. Epidemiology and Early Detection of Cervical Cancer. Oncol Res Treat. 2016;39(9):501–6.
Muñoz N, Bosch FX, de Sanjosé S, et al. Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med. 2003;348(6):518–27.
Zhong G, Wang Y, Xie Q, Lin R, Yao T. HPV-specific risk assessment of cervical cytological abnormalities. BMC Cancer. 2021;21(1):949.
Bernard HU, Burk RD, Chen Z, van Doorslaer K, zur Hausen H, de Villiers EM. Classification of papillomaviruses (PVs) based on 189 PV types and proposal of taxonomic amendments. Virology. 2010;401(1):70–9.
Trottier H, Mahmud S, Costa MC, et al. Human papillomavirus infections with multiple types and risk of cervical neoplasia. Cancer Epidemiol Biomarkers Prev. 2006;15(7):1274–80.
Dickson EL, Vogel RI, Geller MA, Downs LS Jr. Cervical cytology and multiple type HPV infection: a study of 8182 women ages 31–65. Gynecol Oncol. 2014;133(3):405–8.
Li N, Franceschi S, Howell-Jones R, Snijders PJ, Clifford GM. Human papillomavirus type distribution in 30,848 invasive cervical cancers worldwide: Variation by geographical region, histological type and year of publication. Int J Cancer. 2011;128(4):927–35.
Sjoeborg KD, Tropé A, Lie AK, et al. HPV genotype distribution according to severity of cervical neoplasia. Gynecol Oncol. 2010;118(1):29–34.
Nartey Y, Amo-Antwi K, Hill PC, et al. Human papillomavirus genotype distribution among women with and without cervical cancer: Implication for vaccination and screening in Ghana. PLoS ONE. 2023;18(1):e0280437.
Falcaro M, Castañon A, Ndlela B, et al. The effects of the national HPV vaccination programme in England, UK, on cervical cancer and grade 3 cervical intraepithelial neoplasia incidence: a register-based observational study. Lancet. 2021;398(10316):2084–92.
de Sanjosé S, Diaz M, Castellsagué X, et al. Worldwide prevalence and genotype distribution of cervical human papillomavirus DNA in women with normal cytology: a meta-analysis. Lancet Infect Dis. 2007;7(7):453–9.
Cenci M, Rossi F, Pisani T. Detection of 14 High-risk Human Papillomavirus (HPV) Genotypes Within the Italian Cervical Cancer Screening. In Vivo. 2023;37(5):2161–5.
Arbyn M, Weiderpass E, Bruni L, et al. Estimates of incidence and mortality of cervical cancer in 2018: a worldwide analysis. Lancet Glob Health. 2020;8(2):e191–203.
Laake I, Feiring B, Jonassen CM, et al. Concurrent Infection With Multiple Human Papillomavirus Types Among Unvaccinated and Vaccinated 17-Year-Old Norwegian Girls. J Infect Dis. 2022;226(4):625–33.
Okoye JO, Chukwukelu CF, Okekpa SI, Ogenyi SI, Onyekachi-Umah IN, Ngokere AA. Racial Disparities Associated with the Prevalence of Vaccine and Non-Vaccine HPV Types and Multiple HPV Infections between Asia and Africa: A Systematic Review and Meta-Analysis. Asian Pac J Cancer Prev. 2021;22(9):2729–41.
Ji L, Chen M, Yao L. Strategies to eliminate cervical cancer in China. Front Oncol. 2023;13:1105468.
You D, Han L, Li L, et al. Human Papillomavirus (HPV) Vaccine Uptake and the Willingness to Receive the HPV Vaccination among Female College Students in China: A Multicenter Study. Vaccines (Basel). 2020;8(1):31.
Thapa N, Maharjan M, Shrestha G, et al. Prevalence and type-specific distribution of human papillomavirus infection among women in mid-western rural, Nepal- A population-based study. BMC Infect Dis. 2018;18(1):338.
Li K, Li Q, Song L, Wang D, Yin R. The distribution and prevalence of human papillomavirus in women in mainland China. Cancer. 2019;125(7):1030–7.
Baloch Z, Yuan T, Wang B, et al. Ethnic and geographic variations in HPV prevalence and genotype distribution in north-western Yunnan. China J Med Virol. 2016;88(3):532–40.
Perkins RB, Guido RS, Castle PE, et al. 2019 ASCCP Risk-Based Management Consensus Guidelines for Abnormal Cervical Cancer Screening Tests and Cancer Precursors. J Low Genit Tract Dis. 2020;24(2):102–31.
Rosário A, Sousa A, Marinho-Dias J, et al. Impact of high-risk Human Papillomavirus genotyping in cervical disease in the Northern region of Portugal: Real-world data from regional cervical cancer screening program. J Med Virol. 2023;95(1): e28414.
Bukowski A, Hoyo C, Hudgens MG, et al. Extended Human Papillomavirus Genotyping to Predict Progression to High-Grade Cervical Precancer: A Prospective Cohort Study in the Southeastern United States. Cancer Epidemiol Biomarkers Prev. 2022;31(8):1564–71.
Long W, Yang Z, Li X, et al. HPV-16, HPV-58, and HPV-33 are the most carcinogenic HPV genotypes in Southwestern China and their viral loads are associated with severity of premalignant lesions in the cervix. Virol J. 2018;15(1):94.
Juárez-González K, Paredes-Cervantes V, Gordillo-Rodríguez S, et al. High prevalence of human papillomavirus type 66 in low-grade cervical lesions of Mexican women. Arch Virol. 2020;165(11):2633–40.
Wong EL, Cheung AW, Chen Z, et al. Molecular Epidemiology of Human Papillomavirus Infection Among Chinese Women With Cervical Cytological Abnormalities. Front Public Health. 2022;10: 820517.
Nogueira Dias Genta ML, Martins TR, Mendoza Lopez RV, et al. Multiple HPV genotype infection impact on invasive cervical cancer presentation and survival. PLoS One. 2017;12(8):e0182854.
Kim M, Park NJ, Jeong JY, Park JY. Multiple Human Papilloma Virus (HPV) Infections Are Associated with HSIL and Persistent HPV Infection Status in Korean Patients. Viruses. 2021;13(7):1342.
Bai A, Xue P, Li Q, Jiang Y, Qiao Y. Diagnostic value of high-risk HPV other than type 16/18 in high-grade cervical neoplasia among cytology-negative women: A multicenter retrospective study. Cancer Med. 2023;12(13):14794–805.
Chaturvedi AK, Katki HA, Hildesheim A, et al. Human papillomavirus infection with multiple types: pattern of coinfection and risk of cervical disease. J Infect Dis. 2011;203(7):910–20.
Senapati R, Nayak B, Kar SK, Dwibedi B. HPV genotypes co-infections associated with cervical carcinoma: Special focus on phylogenetically related and non-vaccine targeted genotypes. PLoS ONE. 2017;12(11): e0187844.
Yang Z, Cuzick J, Hunt WC, Wheeler CM. Concurrence of multiple human papillomavirus infections in a large US population-based cohort. Am J Epidemiol. 2014;180(11):1066–75.
Liao G, Jiang X, She B, et al. Multi-Infection Patterns and Co-infection Preference of 27 Human Papillomavirus Types Among 137,943 Gynecological Outpatients Across China. Front Oncol. 2020;10:449.
Dickson EL, Vogel RI, Bliss RL, Downs LS Jr. Multiple-type human papillomavirus (HPV) infections: a cross-sectional analysis of the prevalence of specific types in 309,000 women referred for HPV testing at the time of cervical cytology. Int J Gynecol Cancer. 2013;23(7):1295–302.
Wang M, Liang H, Yan Y, et al. Distribution of HPV types among women with HPV-related diseases and exploration of lineages and variants of HPV 52 and 58 among HPV-infected patients in China: A systematic literature review. Hum Vaccin Immunother. 2024;20(1):2343192.
Zhao C, Zhao Y, Li J, Li M, Shi Y, Wei L. Opportunities and challenges for human papillomavirus vaccination in China. Hum Vaccin Immunother. 2024;20(1):2329450.
Man I, Vänskä S, Lehtinen M, Bogaards JA. Human Papillomavirus Genotype Replacement: Still Too Early to Tell. J Infect Dis. 2021;224(3):481–91.
Fischer S, Bettstetter M, Becher A, et al. Shift in prevalence of HPV types in cervical cytology specimens in the era of HPV vaccination. Oncol Lett. 2016;12(1):601–10.
Bogaards JA, van der Weele P, Woestenberg PJ, van Benthem B, King AJ. Bivalent Human Papillomavirus (HPV) Vaccine Effectiveness Correlates With Phylogenetic Distance From HPV Vaccine Types 16 and 18. J Infect Dis. 2019;220(7):1141–6.
Shen Y, Huang Y, Wang W, et al. Prevalence and genotype distribution of HPV infection among women in Xiamen. China Front Microbiol. 2023;14:1130226.
Buttà M, Serra N, Panzarella V, Fasciana T, Campisi G, Capra G. Orogenital Human Papillomavirus Infection and Vaccines: A Survey of High- and Low-Risk Genotypes Not Included in Vaccines. Vaccines (Basel). 2023;11(9):1466.
Hao S, Wang C, Liu S, He J, Jiang Y. HPV genotypic spectrum in Jilin province, China, where non-vaccine-covered HPV53 and 51 are prevalent, exhibits a bimodal age-specific pattern. PLoS ONE. 2020;15(3):e0230640.
Acknowledgements
Acknowledgements Not applicable.
Funding
None.
Author information
Authors and Affiliations
Contributions
QLL designed the experiments. HYZ and XHZ performed the experiments. NH and ZM collected and analyzed the data. NH, ZM and HYL drafted manuscript. All authors read and approved the final manuscript.
Corresponding author
Ethics declarations
Ethics approval and consent to participate
All patients were informed and signed informed consent voluntarily. This study was approved by the ethics committee of Chongqing University Cancer Hospitaland complied with the guidelines outlined in the declaration of Helsinki were followed. The written consent was received from all participants.
Consent for publication
Not applicable.
Competing interests
The authors declare no competing interests.
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.
About this article
Cite this article
Luo, Q., Zhang, H., Zeng, X. et al. HPV specificity and multiple infections and association with cervical cytology in Chongqing, China: a cross-sectional study. BMC Infect Dis 24, 804 (2024). https://doi.org/10.1186/s12879-024-09693-3
Received:
Accepted:
Published:
DOI: https://doi.org/10.1186/s12879-024-09693-3