A survey in Liangshan, Sichuan showed higher human papillomavirus infection rate and cervical cancer risk for Yi Chinese compared to Han Chinese

Introduction

Cervical cancer is the fourth most common malignancy recorded among women worldwide with more than 500,000 new cases and causing 250,000 deaths every year (1). Convincing evidences found in numerous researches indicate that human papillomavirus (HPV) is a main cause for high-grade cervical intraepithelial neoplasia (CIN) and cervical cancer (2,3). Apart from cervical cancer, HPV was reported to be associated with some vulvar and vaginal cancers, anal cancers and head and neck cancers (4). HPV induced cervical cancer is highly avoidable by proper epidemics control protocols. Primary HPV screening is recommended as complement of ThinPrep cytologic test (TCT) in cervical cancer prevention by multiple related medical societies and institutes in America (5) and the 9-valent vaccine licensed 2014 could provide protections against 90% of HPV infections (5). Up to 2021, more than 200 HPV variants had been identified, 14 of which, including types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68, are considered high-risk as they are found highly correlated to some cancers (6,7). Although HPV16 and HPV18 has been considered as the most dangerous types so that urgent colposcopy inspections should be immediately performed once infection detected (8), conflicting results were reported upon estimating risks of these high-risk HPV variants (9,10). Moreover, patient age and HPV type distribution were reported to vary tremendously with factors such as geographical or political regions (11,12).

Another important factor affecting HPV and cervical cancer prevalence is ethnicity, especially for low-income regions. Researches conducted in Romania revealed different infection rate between different ethnic groups (13,14). Similar results were reported between Han and Hani Chinese in Yunnan, China (15), but another study argued that urban/rural residence has greater effect than ethnicity (16). Besides, apart from HPV infections, HIV (human immunodeficiency virus) is another factor bringing particularly high risk of cervical cancer and a focus on HPV-related cervical cancer research (17). Yi Chinese is an ethnic minority group who mainly reside in Yunnan, Guangxi, Guizhou and Sichuan province of China and the main minority group in Liangshan, Sichuan which was reported to be one of the low-income areas with severe HIV prevalence in China. In a HIV survey conducted in Liangshan state from 2011 to 2014, 94.08% of the HIV carriers were Yi Chinese (18). The HIV prevalence in this area was first caused by illegal injection drug uses and substandard healthcare condition due to poverty (19). Afterward, sex transmission became the main cause of HIV infection afterward, especially for Yi women. Another research in 2020 reported that, compared to men, more women were infected through sex intercourses, of which 72.87% were intercourses outside marriage (20). Yi women in Liangshan could be constantly exposed to high cervical cancer risks under the interaction of HIV infection and ethnicity.

The main cervical cancer prevention approaches are screening and vaccination. However, in China, the burden of HPV-related cervical cancer is high but the availability of vaccination was relatively limited (21). Therefore, screening composed by multiple tests became the main prevention procedure (22). However, large scare cervical carcer screens were not available to women in Liangshan prior to this research. The screening protocol evolved with understanding the HPV prevalence in China, leading to a protocol with HPV tests and cytologic tests as primary tests and confirmation with colposcopy and biopsies. To optimise the application of screening and vaccination, a model built on data including screening coverage, test performance and number of different health states was proposed (23). To yield cervical cancer prevention strategies fulfilling expectations with such model and support further study on cervical cancer risk of HIV infections, basic statistics of HPV prevalence are crucial.

In this study, a 3-year survey including HPV genotyping, TCT and colposcopy guided biopsy was conducted in Liangshan, Sichuan, China to identify local cervical cancer and HPV prevalence. TCTs and HPV tests are standard tests adopted in primary cervical cancer screening (7) and related researches (24) while biopsies provide key evidence for diagnoses. This study pioneered comprehensive investigations of HPV infection and cervical cancer risk profiles on all female local residents susceptible to HPV in Liangshan, especially Yi women who were reported suffering the prevalence of another sexually transmitted virus HIV (20). Moreover, the screening itself could provide testing equipment and related medical training to improve local healthcare standards on related disease control. We present this article in accordance with the STROBE reporting checklist (available at https://gpm.amegroups.com/article/view/10.21037/gpm-23-38/rc).

Methods

Study design

A 3-year survey starting on December 2017 for cervical cancer screening was conducted in Liangshan state, Sichuan. Written consents were acquired from all participants. Personal information including age, ethnicity, personal contact and address, was collected from the resident identification cards. The overall study design was illustrated in Figure 1. At the beginning of the survey, all participants were tested with TCT and HPV genotyping. Colposcopy directed biopsies were applied to participants who had abnormality observed with TCT or were tested positive for HPV16/18 or were willing to receive further testing with cervical biopsies. Among the participants tested by biopsies, those with no lesion or CIN grade 1 (CIN1) would be contacted by researchers next year for follow-up testing while others with more severe lesions would have their data finalised and transferred for further treatments. Same screening protocol was demonstrated on the follow-up testing in the following year until the participants progressing to CIN grade 2 (CIN2) or worse or the end of the survey. At the last year of this survey, all participants not progressing to CIN2 or worse would be called back for rescreening. In the process of this survey, samples been improperly collected, stored, transported or from excluded participants would be discarded. Abnormal results caused by sample quantity below detection limits or mistakes in experiment operations would also be excluded from analyses.

Figure 1 Cervical cancer screening protocol and study design. All participants were tested with TCT and HPV genotyping. Colposcopy directed biopsies were applied to participants who had abnormality observed with TCT or were tested positive for HPV 16/18 or were willing to receive further testing with cervical biopsies. Among the participants tested by biopsies, those with no lesion or CIN1 would be revisit next year while others with more severe lesions would have their data finalised and transferred for further treatments. hrHPV, high-risk human papillomaviruses; NILM, negative for intraepithelial lesion or malignancy; ASCUS, atypical squamous cells of undetermined significance; CIN1, cervical intraepithelial neoplasia grade 1; CIN2, cervical intraepithelial neoplasia grade 2; TCT, Thinprep cytologic test.

Participants

In order to investigate prevalence in natural population, an involvement of at least 4,000 participants was designed for this study and the participants were recruited without stratification through cancer screening promotions and advertisements in communities in 3 main resident regions of Liangshan state at the beginning of the survey. The participants were selected based on the following inclusion criteria: (I) women of age between 21 to 65 years with sex experience; (II) willing to receive cervical cancer screening tests including colposcopies and biopsies; (III) willing to receive related follow-up tests up to three years. Participants with any condition described in the following criteria were excluded from this study: (I) women in pregnancy or within 8 weeks after delivery; (II) was diagnosed cervical precancerous lesions or cervical cancer or had received corresponding treatments; (III) had received HPV vaccination; (IV) with a history of radiotherapy or chemotherapy, a complete hysterectomy; (V) received cervicectomy within 12 months prior to this study.

Cervical sample collection

Cervical cells were collected by wiping cervix with a cervical brush. The cells were then immediately washed into ThinPrep PreservCyt preservation solution for HPV genotyping and TCT.

HPV genotyping

HPV genotyping was performed using a specialised HPV genotyping panel with polymerase chain reaction (PCR)-reverse dot hybridization (Yaneng Bioscience, Shenzhen, China). Sample DNA was extracted, amplified and then hybridised in automatic hybridization platform (Yaneng Bioscience) according to manufacture constructions. Fifteen HPV variants (type 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66 and 68) were tested in this survey.

TCT

ThinPrep cytology slides were prepared with cervical cells kept in preservation solution using a BD Totalys^TM SlidePrep automatic platform (BD Diagnostics, Burlington, NC, USA). All slides were then examined according to Bethesda 2001 criteria (25) by experienced pathologists. The results were described with one of the following four statuses: NILM (negative for intraepithelial lesion or malignancy), ASC-US (atypical squamous cells of undetermined significance), LSIL (low-grade squamous intraepithelial lesion) and HSIL (high-grade squamous intraepithelial lesions).

Colposcopy guided biopsy

Cervical biopsies were performed under colposcope when abnormality was observed in TCT or the participant was tested positive for HPV16/18. Pathological diagnoses, including no lesion, CIN1–3 and cervical cancer, were made accordingly.

Statistical analyses

For age specified analyses, participants were divided into 5 age-strata where every stratum consists of a 10-year period making up a total range from age 20 to 69. The cytology results were primarily divided into normal and abnormal with normal being NILM and abnormal being the others. Meanwhile, histology diagnosis results were categorised according to the follow-up protocol, where CIN2 and worse were considered pathologically decisive and others were sceptical. The ethnicity of participants was identified according to information on their resident identity card. Women of various ethnic minorities were involved in this study but the numbers were insufficient for reliable conclusion to be drawn for most of the minority and thus only minority of Yi was analysed separately while other minorities were grouped as others. The infection rates of different ethnic groups were calculated with and without adjustment with age distributions for analysing age structure effects on infection rates. Samples with missing data were excluded from further analyses. Confidence intervals (CIs) for proportion were calculated using Wilson scores. Two-sample proportion Z tests were used for equality estimations between infection rates and detection rates. Chi-squared test was used to examine difference between HPV variant profiles of Yi and Han Chinese. Statistical analyses were performed with R 3.6.

Ethical consideration

All procedures performed in this study were approved by the ethics committee of West China Second University Hospital of Sichuan University (2022 Medical scientific research for ethical approval No. 129). This study was conducted in accordance with the Helsinki Declaration (as revised in 2013) and written informed consent was obtained from all participants for their anonymized information to be published.

Results

Overall, 5,125 women participated the survey. However, 361 records were found missing during follow-up, 30 records were discarded for missing age or ethnical information and another 11 records were discarded for unreliable TCT results. Lastly, records of 4,723 women, of whom 3,813 were Han Chinese, 786 were ethnic minority Yi and 124 were of other ethnic minority groups, were included in this study. Five hundred and fifteen participants were tested positive for HPV at the beginning of this study, making up a total infection ratio of 10.90% (Table 1). The most prevalence variant is HPV52 (Table 2). Two thousand nine hundred and ninety patients come back for screening on the third year, of whom 2,625 were not being followed up. Overall, 420 participants were tested positive for HPV at the last screen, including the 292 infected from participants not being followed up. Throughout the entire period of the survey, cytological abnormality was observed on 298 participants and cervical biopsies confirmed 63 cases with CIN2 or worse (Table 1). Progressions from CIN1 to higher level of lesion were observed in this survey. TCTs were performed alone site with HPV genotyping according to the standard screening protocol but showed different performances on detecting lesions.

Details of screening results

In this study, cervical cancers screening was performed using HPV genotyping and TCT. Participants involved were within the age of 20 to 69 with an average of 44.05 years old. The ages were symmetrically distributed with one peak on age strata of 40–49. Although many participants did not response to follow-up, age distribution of those return for screening at the third year was consistent with a subtle change of mean age to 44.46. Five hundred and fifteen patients were found infected by HPV (Table 1) and the 4 most prevalent variants were 52 (142 cases), 58 (80 cases), 53 (59 cases) and 16 (50 cases), while the 4 least prevalent variants were 45 (4 cases), 66 (11 cases), 35 (13 cases) and 31 (18 cases). According to screening protocol (Figure 1), at the baseline stage, 702 participants with HPV infections or abnormality on TCT but no serious lesion should be revisited after 12 months and 38 patients with lesions worse than CIN2 would leave this study for further medical treatments. Given hundreds of patients were found with lesion indications, only 120 colposcopy guided biopsies were performed for further diagnosis.

At the last stage, only 2,990 participants were willing to join this survey. Compared to the results from the baseline stage, significantly less HPV infected and TCT abnormalities were found but more colposcopy tests were performed (Table 1), although the rate of lesions worse than CIN2 was also significantly lower.

Progression on follow-up patients

Although follow-up tests were recommended 702 participants with indications, some of them were not willing to accept further testing or postpones follow-up tests. As a result, 511 patients attended follow-up screening in the first year, 512 patients attended in the second year and 365 patients attended in the third year (Table 3). According to the follow-up protocol, patients would only leave the cohort when progressing to lesions worse than CIN2. However, more patients refused follow-up tests due to underestimation or ignorance of the potential cancer risks. Among the cohort been tested, number of patients been infected or with TCT abnormality or with lesions worse than CIN2 were decreasing throughout the time period of this study, except for a mild rebound of number of high-level lesions with an increase of colposcopy test number in the last year. It is fortunate and well known that only a small proportion of HPV infections or lesions progress to cancers, but the risks should be acknowledged by most people. Biopsy guided by colposcopy is the gold standard for diagnosing cervical cancers, but it is an invasive test inducing rejections from patients. The increase of use of such test may suggest a higher acceptance within the cohort.

Higher cancer risk within ethnic minority Yi

In this survey, 63 cases of lesions worse than CIN2 were discovered, of which 49 cases were founded on Han women and 13 cases were found on Yi women. Higher cervical cancer risk within ethnic minority Yi (1.68%) compared to the ethnic majority Han Chinese (1.29%) raised concerns (Table 4). No significantly difference was identified on the profile of most prevalence HPV variants (P value =0.29) and the fact of involved Yi women being younger does not fully justify the higher HPV infection rate and severe lesion rate (Tables 2,4). The most prevalent HPV variants were 52, 58 and 53 which were identical in both Han and Yi and the profiles of other less prevalent variants showed no significant difference. However, apart from the severe lesion rate, the HPV infection rate acquired from baseline data was also significantly higher for Yi Chinese (13.10%) compared to Han (10.46%) (P value =0.03). Age-specific ratio analysis (Table 5) demonstrated that HPV infections were still more prevalent in Yi Chinese within every age stratum and in total (13.46% to 10.41% in Han) after normalisation by age and their 95% CIs did not overlap. Statistical significance test for difference of cancer risks was not demonstrated for insufficient sample size but highly similar rates of severe lesions upon HPV infections were observed from baseline data for Han (27/399, 6.77%) and Yi Chinese (7/103, 6.80%). Therefore, based on these infection rates, Yi women were more susceptible to severe lesion than Han women. Besides, despite more participants being age between 40 and 50, the infection rates were lowest in this age strata for both ethics (Figure 2).

Figure 2 Comparison of infection rate distribution on age between Han and Yi Chinese. Based on the infection rates, infected Yi women were more likely to progress into severe lesion than Han women. The infection rate was lowest in age strata of [40, 49] for both ethics.

Screening power of HPV genotyping and TCT

HPV genotyping and TCT are two methods wildly used in cervical cancer screening and were both adopted in this study. Throughout the entire study, 7,459 HPV tests and 8,597 TCT tests were conducted (Table 6). Overall, HPV tests were more sensitive but less specific toward lesions compared to TCTs. It is worth noticing that for lower-level lesions such as CIN1–2, sensitivity of HPV test was equivalent to or even lower than that of TCT in this survey. However, HPV tests showed significantly higher sensitivity toward CIN3 and worse lesions (P value =0.04). Additionally, when history results were taken into consideration, of the 25 CIN2 and worse cases diagnosed during the follow-up and call-back process, 23 had HPV infection history while only 20 had been founded abnormal with TCTs.

Discussion

Distinct HPV prevalence profile

HPV screening for early cervical cancer detection has been conducted in many different places across China (26-30). HPV16 was reported as the most commonly detected variant responsible for more than 20% of the infections in most of researches (26-28,31) while some reported different results (29,30). In this study, HPV52 was found significantly more prevalent than HPV16 (Tables 2,4), which was consistent with Yan et al. (29). Moreover, although all researches mentioned above agreed HPV16 bring highest risk in developing cervical cancer with infection, a unanimous agreement on its risk magnitude compared to other HPV variants has not been achieved (32).

HPV variant prevalence is highly area specific so that adjusting vaccine distribution accordingly should improve reginal vaccine efficiency. Up to 2023, 3 type of HPV vaccines has made available in China: bivalent, quadrivalent and nonavalent vaccine, although the availability of these vaccines varies across areas. All 3 vaccines protect against HPV16 and HPV18, but the most significant difference of these vaccine is the coverage of high-risk variant 31, 33, 45, 52 and 58 which are only included by the nonavalent vaccine (7,33). HPV52 and HPV58 were reported to be most prevalent variants in many areas of China (29) including the area studied by this research. Administrating nonavalent vaccines in these areas could provide better protections compared to other vaccines (34-36), although all vaccines offer notable protection against cervical cancers.

The standard cervical cancer screening protocol adopted by this study only emphasised HPV16 and HPV18, while other high-risk variants were treated equally with all other variants. In this study, high-risk HPV variants such as HPV52 and HPV58 were associated to even more high-level lesions than HPV16 deal to much higher prevalence. Although these high-risk variants might carry lower cancer risk than HPV16, the accumulative risk they bring in reginal prevalence should not be underestimated (37,38). Discriminative treatments between high-risk variants and low-risk variants should be applied. On the other hand, persistent infections should raise more concerns and regular monitoring of high-risk HPV variants infections could be applied. Researches showed that persistent infections could increase cancer risk (39,40) but the annual body check recommended by the screening protocol might be misled by seasonal migration occurred at the beginning of the year. HPV genotyping is a cheap and effective screening method and increasing HPV test frequency for people with high-risk variant infection could improve cancer risk control with low cost.

Cancer risk control protocol

Controlling HPV prevalence would be crucial for reducing cervical cancer risk for residence in Liangshan state, especially for Yi women. Studies showed that many patients with high risk for cancer or severe lesions had not been addressed as not receiving related tests (31). In this study, a notable number of participants were reluctant to receive the follow-up tests, making it difficult to discover novel lesions or monitor lesion progressions. Lacks of awareness of importance of cervical cancer screening and limited access to qualified institutes for proper testing largely reduce people’s willing for participating. Thus, establishing and promoting cervical cancer screening project in Liangshan state should be the first step of cervical cancer control in this area. When conducting screenings for this study, the medical team introduced cervical cancer prevention protocols to the state, together with related testing facilities and specialised techniques to establish a system providing sustainable service.

As facility development and screening progression in this study, a rise in colposcopy guided biopsy operations was observed. Only 120 biopsies were conducted at the beginning compared to nearly 200 biopsies conducted in the last year despite the significant decrease of total number of participants, showing a distinct higher acceptance of this operation within participants. Biopsy is the gold standard for diagnosing cervical cancers (41). Such increase of acceptance indicated and better social awareness of the importance of cancer screening and control.

In the period of this research, cervical cancer screenings were more relied on TCT than HPV testing results. The results of this research indicated that HPV genotyping might be more sensitive toward high-level lesions. Besides, HPV genotyping could be fully automated to minimise labour requirement and human interpretations and could be more easily applied (42,43). Therefore, HPV genotyping results worth more attentions and implemented more widely in cervical cancer screening.

Research limitations

The findings in details and reliability of figures and conclusions of this study were mainly limited by the population and sampling bias involved. Number of cases being positive with HPV infection or abnormal with TCT or identified as CIN2 or worse was insufficient for detail calculations such as cancer rate by different HPV variant infection. The research samples were collected only from a few locations of Liangshan state due to the limit transportation and facility so that considerable bias could be introduced. On the other hand, according to Yang et al., 10.9% of the Yi students in secondary school, who is of age 12 to 15, have sex experience and the average first sex experience age for Yi women is 17 (44). This indicates that women under 18 should be included for sexual transmitted diseases screening or studies involving Yi population. Also, the design not including newly occurred infections during follow-up period and follow-up annually rather than more frequently denied the possibility of observing the deterioration process starting from initial HPV infection.

Conclusions

In this study, a survey in natural population for cervical cancer screening was conducted without class adjustment, the overall HPV infection rate observed was 10.90%. HPV16 was found to be the most cervical cancer related variant while HPV52 was found to be the most prevalent. Significantly higher HPV infection rate was observed on the Yi women compared to Han women resulting higher severe lesion rate and indicating that controlling the prevalence of HPV, especially the high-risk variants, amid Yi women could be the key of cervical cancer prevention in Liangshan state.

Acknowledgments

Funding: This research was supported by the National Key Research and Development Program of China (No. 2016YFC1302901 to Y.W.) and Sichuan Provincial Key Laboratory of Shock and Vibration of Engineering Materials and Structures, Southwest University of Science and Technology (No. 19ZDYF to R.Y.).

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://gpm.amegroups.com/article/view/10.21037/gpm-23-38/rc

Data Sharing Statement: Available at https://gpm.amegroups.com/article/view/10.21037/gpm-23-38/dss

Peer Review File: Available at https://gpm.amegroups.com/article/view/10.21037/gpm-23-38/prf

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://gpm.amegroups.com/article/view/10.21037/gpm-23-38/coif). R.Y. serves as an unpaid Editorial Board Member of Gynecology and Pelvic Medicine from June 2022 to May 2024. R.Y. also reported funding for this research from Sichuan Provincial Key Laboratory of Shock and Vibration of Engineering Materials and Structures, Southwest University of Science and Technology (19ZDYF). Y.W. raised funding for this research from the National Key Research and Development Program of China (2016YFC1302901). Q.F., B.R. and Lianyun Wu are employees of Yaneng Bioscience (Shenzhen) Co. Ltd. and reported receipt of test reagents for this research from Yaneng Bioscience (Shenzhen) Co. Ltd. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were approved by the ethics committee of West China Second University Hospital of Sichuan University (2022 Medical scientific research for ethical approval No. 129). This study was conducted in accordance with the Helsinki Declaration (as revised in 2013) and written informed consent was obtained from all participants for their anonymized information to be published.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Bhatla N, Aoki D, Sharma DN, et al. Cancer of the cervix uteri. Int J Gynaecol Obstet 2018;143:22-36. [Crossref] [PubMed]
2. Ho GY, Burk RD, Klein S, et al. Persistent genital human papillomavirus infection as a risk factor for persistent cervical dysplasia. J Natl Cancer Inst 1995;87:1365-71. [Crossref] [PubMed]
3. Kjaer SK, van den Brule AJ, Paull G, et al. Type specific persistence of high risk human papillomavirus (HPV) as indicator of high grade cervical squamous intraepithelial lesions in young women: population based prospective follow up study. BMJ 2002;325:572. [Crossref] [PubMed]
4. Okunade KS. Human papillomavirus and cervical cancer. J Obstet Gynaecol 2020;40:602-8. [Crossref] [PubMed]
5. Huh WK, Ault KA, Chelmow D, et al. Use of primary high-risk human papillomavirus testing for cervical cancer screening: interim clinical guidance. Gynecol Oncol 2015;136:178-82. [Crossref] [PubMed]
6. Crosbie EJ, Einstein MH, Franceschi S, et al. Human papillomavirus and cervical cancer. Lancet 2013;382:889-99. [Crossref] [PubMed]
7. Wang R, Pan W, Jin L, et al. Human papillomavirus vaccine against cervical cancer: Opportunity and challenge. Cancer Lett 2020;471:88-102. [Crossref] [PubMed]
8. Castle PE, Stoler MH, Wright TC Jr, et al. Performance of carcinogenic human papillomavirus (HPV) testing and HPV16 or HPV18 genotyping for cervical cancer screening of women aged 25 years and older: a subanalysis of the ATHENA study. Lancet Oncol 2011;12:880-90. [Crossref] [PubMed]
9. Carozzi F, De Marco L, Gillio-Tos A, et al. Age and geographic variability of human papillomavirus high-risk genotype distribution in a large unvaccinated population and of vaccination impact on HPV prevalence. J Clin Virol 2014;60:257-63. [Crossref] [PubMed]
10. Aro K, Nieminen P, Louvanto K, et al. Age-specific HPV type distribution in high-grade cervical disease in screened and unvaccinated women. Gynecol Oncol 2019;154:354-9. [Crossref] [PubMed]
11. 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;7:453-9. [Crossref] [PubMed]
12. Aoki ES, Yin R, Li K, et al. National screening programs for cervical cancer in Asian countries. J Gynecol Oncol 2020;31:e55. [Crossref] [PubMed]
13. Şuteu O, Blaga ML, Nygård M, et al. Prevalence of positive screening test results and agreement between cytology and human papillomavirus testing in primary cervical cancer screening in North-Western Romania. Eur J Cancer Prev 2020;29:141-8. [Crossref] [PubMed]
14. Ilisiu MB, Hashim D, Andreassen T, et al. HPV Testing for Cervical Cancer in Romania: High-Risk HPV Prevalence among Ethnic Subpopulations and Regions. Ann Glob Health 2019;85:89. [Crossref] [PubMed]
15. Baloch Z, Yue L, Yuan T, et al. Status of Human Papillomavirus Infection in the Ethnic Population in Yunnan Province, China. Biomed Res Int 2015;2015:314815. [Crossref] [PubMed]
16. Lu H, He H, Qin J, et al. Populations at high risk of cervical cancer in Guangxi Province: Findings from two screening projects in a minority area of South China. J Med Screen 2022;29:44-52. [Crossref] [PubMed]
17. Castle PE, Einstein MH, Sahasrabuddhe VV. Cervical cancer prevention and control in women living with human immunodeficiency virus. CA Cancer J Clin 2021;71:505-26. [Crossref] [PubMed]
18. Ji-Ke CN, Yang SJ, Pei R, et al. Study on the risk factors for HIV infection among Yi population based on the HIV/AIDS sentinel surveillance of community population. Modern Preventive Medicine 2018;45:1483-6.
19. Zhu C, Song X, Jiang Q. Review on the influence factors of AIDS epidemic and control in Liangshan Prefecture Sichuan Province of China. Fudan University Journal of Medical Sciences 2015;42:675-9.
20. Liu L, Liu L, Zhang L, et al. Analysis on premarital HIV screening results in Liangshan, Sichuan, 2014-2020. Disease Surveillance 2022;37:1074-8.
21. Wang H, Jiang Y, Wang Q, et al. The status and challenges of HPV vaccine programme in China: an exploration of the related policy obstacles. BMJ Glob Health 2023;8:e012554. [Crossref] [PubMed]
22. Branch of Cancer Prevention and Control, Chinese Preventive Medicine Association. Chinese Obstetrics and Gynecology Association Colposcopy and Cervical Neoplasia Committee; Chinese Society of Colposcopy and Cervical Pathology of China Health Birth Science Association; Beijing Medical Doctor (Technician) Society of Laboratory Medicine. Chinese expert consensus on the use of human papillomavirus nucleic acid testing for cervical cancer screening (2022). Zhonghua Yi Xue Za Zhi 2023;103:1184-95.
23. Zou Z, Fairley CK, Ong JJ, et al. Domestic HPV vaccine price and economic returns for cervical cancer prevention in China: a cost-effectiveness analysis. Lancet Glob Health 2020;8:e1335-44. [Crossref] [PubMed]
24. Tang D, Liao GD, Cao HY, et al. Detection of CDR3s diversity and its prediction of persistent high-risk HPV infection and cervical intraepithelial neoplasia risk: a prospective study. Gynecol Pelvic Med 2022;5:22. [Crossref]
25. Solomon D, Davey D, Kurman R, et al. The 2001 Bethesda System: terminology for reporting results of cervical cytology. JAMA 2002;287:2114-9. [Crossref] [PubMed]
26. Jiang L, Tian X, Peng D, et al. HPV prevalence and genotype distribution among women in Shandong Province, China: Analysis of 94,489 HPV genotyping results from Shandong's largest independent pathology laboratory. PLoS One 2019;14:e0210311. [Crossref] [PubMed]
27. Zeng Z, Yang H, Li Z, et al. Prevalence and Genotype Distribution of HPV Infection in China: Analysis of 51,345 HPV Genotyping Results from China's Largest CAP Certified Laboratory. J Cancer 2016;7:1037-43. [Crossref] [PubMed]
28. Chen Z, Wang Q, Ding X, et al. Characteristics of HPV prevalence in Sichuan Province, China. Int J Gynaecol Obstet 2015;131:277-80. [Crossref] [PubMed]
29. Yan X, Shen L, Xiao Y, et al. Prevalence, characteristics, and distribution of HPV genotypes in women from Zhejiang Province, 2016-2020. Virol J 2021;18:208. [Crossref] [PubMed]
30. Liu H, Zeng C, Jiang M, et al. Study on the prevalence and subtypes of human papillomavirus infection among women in the Xuhui District, Shanghai City, China. Transl Cancer Res 2023;12:2923-31. [Crossref] [PubMed]
31. Li K, Li Q, Song L, et al. The distribution and prevalence of human papillomavirus in women in mainland China. Cancer 2019;125:1030-7. [Crossref] [PubMed]
32. Li W, Meng Y, Wang Y, et al. Association of age and viral factors with high-risk HPV persistence: A retrospective follow-up study. Gynecol Oncol 2019;154:345-53. [Crossref] [PubMed]
33. Wei L, Xie X, Liu J, et al. Elimination of Cervical Cancer: Challenges Promoting the HPV Vaccine in China. Indian J Gynecol Oncol 2021;19:51. [Crossref] [PubMed]
34. Cheng L, Wang Y, Du J. Human Papillomavirus Vaccines: An Updated Review. Vaccines (Basel) 2020;8:391. [Crossref] [PubMed]
35. Serrano B, Alemany L, Ruiz PA, et al. Potential impact of a 9-valent HPV vaccine in HPV-related cervical disease in 4 emerging countries (Brazil, Mexico, India and China). Cancer Epidemiol 2014;38:748-56. [Crossref] [PubMed]
36. Joura EA, Giuliano AR, Iversen OE, et al. A 9-valent HPV vaccine against infection and intraepithelial neoplasia in women. N Engl J Med 2015;372:711-23. [Crossref] [PubMed]
37. Zhu X, Wang Y, Lv Z, et al. Prevalence and genotype distribution of high-risk HPV infection among women in Beijing, China. J Med Virol 2021;93:5103-9. [Crossref] [PubMed]
38. Wang T, Luan L, Deng J, et al. Prevalence and human papillomavirus (HPV) genotype distribution in Suzhou, China. Hum Vaccin Immunother 2023;19:2241309. [Crossref] [PubMed]
39. Bosch FX, Lorincz A, Muñoz N, et al. The causal relation between human papillomavirus and cervical cancer. J Clin Pathol 2002;55:244-65. [Crossref] [PubMed]
40. Bodily J, Laimins LA. Persistence of human papillomavirus infection: keys to malignant progression. Trends Microbiol 2011;19:33-9. [Crossref] [PubMed]
41. Wentzensen N, Massad LS, Mayeaux EJ Jr, et al. Evidence-Based Consensus Recommendations for Colposcopy Practice for Cervical Cancer Prevention in the United States. J Low Genit Tract Dis 2017;21:216-22. [Crossref] [PubMed]
42. WHO. Evidence-Based Consensus Recommendations for Colposcopy Practice for Cervical Cancer Prevention in the United States. second edition. c2021. [cited 2023 Oct 27]. Available online: https://www.who.int/publications/i/item/9789240030824
43. Fontham ETH, Wolf AMD, Church TR, et al. Cervical cancer screening for individuals at average risk: 2020 guideline update from the American Cancer Society. CA Cancer J Clin 2020;70:321-46. [Crossref] [PubMed]
44. Yang S, Luo M, Zhang S, et al. Overview on culture and customs related to AIDS epidemic and prevention among Yi people in Liangshan. Chinese Journal of AIDS & STD 2017;23:271-4.