Assessment of a Risk-Based Stratified Management Strategy for Cervical Cancer Screening in Central China: A Real-World Study across Diverse Populations of 223,533 Opportunistic and 43,102 Health Check-up Participants Over a Decade

doi:10.21203/rs.3.rs-5240196/v1

Download PDF

Research Article

Assessment of a Risk-Based Stratified Management Strategy for Cervical Cancer Screening in Central China: A Real-World Study across Diverse Populations of 223,533 Opportunistic and 43,102 Health Check-up Participants Over a Decade

https://doi.org/10.21203/rs.3.rs-5240196/v1

This work is licensed under a CC BY 4.0 License

You are reading this latest preprint version

Background: The evolving landscape of cervical cancer screening emphasizes risk-based stratification for effective management. This study aims to assess the applicability of a risk-based cervical cancer screening and management strategy in opportunistic screening populations at outpatient clinics and regular health check-up populations in central China.

Methods: The study validated the screening management strategy recommended by the 2019 ASCCP guidelines for 1-year and 3-year follow-up intervals in opportunistic screening and health check-up populations. Data were collected from a large tertiary hospital in central China, including 223,533 outpatient records from April 2012 to April 2022 and 43,102 health check-up records from April 2017 to April 2022. High-risk human papillomavirus (hrHPV) infection rates, cytology results, and subsequent high-grade cervical intraepithelial neoplasia (CIN3+) incidences were evaluated across different age groups. Follow-up data were examined to discern the effectiveness of risk-based management.

Results: The study revealed significant prevalence of hrHPV infection, with overall positivity rates of 18.17% in opportunistic screening and 13.22% in health check-up populations. Among screened individuals, the prevalence of CIN3+ exhibited age-related differences. Specifically, among individuals meeting the follow-up criteria, only the 25-65 years old group in the 1-year follow-up cohort had CIN3+ detection, with a prevalence of 0.47% in the outpatient population and 0.09% in the health check-up population.

Conclusions: The CIN3+ detection rates align with expectations, supporting the applicability of the ASCCP approach in varied screening settings. This study provides valuable insights into the real-world implementation of risk-based cervical cancer screening, contributing to the ongoing paradigm shift towards risk-based stratification. It underscores the importance of continuous efforts to refine screening protocols on a global scale.

Cervical cancer screening

risk-based management

CIN3+

outpatient

health check-up

Central China

Cervical cancer remains a significant global public health issue, with an estimated 570,000 new cases and 311,000 deaths worldwide in 2020¹. Notably, 88.1% of new cases and 91.4% of fatalities occurred in low- and middle-income countries^2,3. Recognizing this challenge, the World Health Organization has launched the "Accelerating the Elimination of Cervical Cancer as a Public Health Problem" global strategy², with the goal of elimination by 2030, emphasizing comprehensive prevention, early detection, and treatment interventions.

In pursuit of this goal, screening guidelines have evolved over time to enhance the efficiency and accuracy of screening strategies^4,5. Epidemiological evidence suggests that in the general population, the risk of developing precancerous lesions within five years after a negative result in HPV testing is less than 0.15%⁶. High-risk human papillomavirus (hrHPV) testing has emerged as a primary screening tool due to its high sensitivity⁷. However, not all HPV infections progress to precancerous or cancerous stages, HPV testing cannot differentiate between transient and persistent infections. Its lower specificity may potentially lead to overdiagnosis and overtreatment⁸. Hence, there is a pressing need to develop improved risk stratification measures to enhance the precision of cervical cancer screening.

In 2019, the American Society for Colposcopy and Cervical Pathology (ASCCP) introduced risk-based management strategies that incorporate individual risk factors to determine appropriate follow-up intervals⁹. This approach, informed by the Kaiser Permanente Northern California (KPNC) study, tailors follow-up based on current and prior screening results. Even with the same current screening result, different management recommendations may arise based on the assessment of prior screening history. General assessment principles include: if the current high-grade cervical intraepithelial neoplasia (CIN3+) risk is ≥ 4%, immediate colposcopy or treatment is recommended; if the current CIN3 risk is < 4%, the 5-year risk of CIN3 + is evaluated to determine whether the patient should undergo follow-up after 1, 3, or 5 years¹⁰. This risk-based approach aims to optimize screening efforts and minimize unnecessary interventions, promoting personalized patient management. However, its applicability in diverse populations, especially in underdeveloped regions, remains largely unexplored.

China, bearing a substantial burden of cervical cancer globally, reported 109,700 new cases and 59,100 deaths in 2020, constituting 18.2% and 17.3% of the global total, respectively³. The validation of the ASCCP-recommended risk-based screening model in China is of paramount importance, not only for the nation itself but also for other middle- and low-income regions facing similar challenges.

This study aims to evaluate the risk-based strategy for cervical cancer screening within opportunistic and routine check-up populations in central China. Ten years of outpatient data (2012–2022) and five years of health check-up data (2017–2022) were analyzed from a prominent tertiary hospital. Participants following the 2019 ASCCP guidelines' 1-year and 3-year follow-up criteria were included. By conducting a thorough evaluation of the risk-based approach within the Chinese context, we aspire to contribute to global endeavors aimed at alleviating the burden of cervical cancer and advancing the objective of eliminating cervical cancer as a public health concern.

Study Population

Data were obtained from the Department of Obstetrics and Gynecology at Central South University Xiangya Hospital. The study encompassed two groups: an outpatient cohort of 223,533 individuals screened between April 2012 and April 2022, and a health check-up cohort of 43,102 individuals screened from April 2017 to April 2022. The outpatient group consisted of patients seeking medical attention for conditions such as uterine fibroids, menstrual irregularities, excluding those with cervical cancer-related symptoms. The health check-up group consisted of individuals who regularly participated in comprehensive health examinations, including cervical cancer screening.

Cervical Cancer Screening Methods

HPV Testing

High-risk HPV testing utilized the Cobas 4800 System (Roche Diagnostics Corporation, Indianapolis, Indiana) or Hybrid Capture 2 assays (Qiagen, Gaithersburg, Maryland). The HC2 and Cobas tests collectively detect 13 high-risk HPV types (HPV-16, -18, -31, -33, -35, -39, -45, -51, -52, -56, -58 and 59), with Type 66 included in the Cobas test. Procedures followed manufacturers' instructions and were chosen based on clinician and patient preferences.

Cervical Cytology Examination

Cervical cytology samples were collected by experienced gynecologists using separate samples from those for HPV testing. These samples were prepared using the liquid-based cytology methodology. All test slides underwent thorough screening, interpretation, and reporting processes under the supervision of pathologists. The screening and reporting procedures adhered to the 2014 Bethesda System criteria and terminology.¹¹. The classification of cytology results was categorized as follows: NILM (negative for intraepithelial lesions or malignancy), ASC-US (atypical squamous cells of undetermined significance), LSIL (low-grade squamous intraepithelial lesion), ASC-H (atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion), HSIL (high-grade squamous intraepithelial lesion), SCC (suspicious for squamous cell carcinoma), and AGC (atypical glandular cells).

Pathological Follow-up

Diagnostic specimens included biopsies, curettage, excision procedures, or hysterectomies performed within 6 months post-screening. Histopathologic results were categorized into four primary groups according to the 2020 WHO classification¹²: 1) negative, 2) cervical intraepithelial neoplasia (CIN) grade 1, 3) CIN2, and 4) CIN3 and more severe lesions (CIN3+), including CIN3, squamous cell carcinoma, endocervical adenocarcinoma in situ, and differentiated adenocarcinoma. Diagnostic interpretations were rigorously verified through the application of immunohistochemical stains for p16/Ki-67 and further reviewed by a second pathologist to ensure accuracy. In cases with multiple samples, the most severe diagnosis was recorded.

Statistical Analysis

Statistical analysis was conducted using GraphPad Prism version 8.0. Descriptive statistics were employed to provide a summary of the key characteristics within the study population. The associations between different variables were examined using Chi-square tests. A significance threshold of p < 0.05 was utilized to determine statistical significance.

Cervical Cancer Screening Patterns in Outpatient Population

In accordance with the 2019 ASCCP guidelines, patients undergoing cervical cancer screening were stratified into three age groups: <25 years, 25–65 years, and > 65 years⁹.

In the outpatient cohort of 223,533 patients (April 2012 - April 2022) (Table 1), 40,619 (18.17%) tested positive for hrHPV (Fig. 1A). Genotyping revealed an HPV-16 infection rate of 19.86%, HPV-18 at 5.46%, and others 12 types at 74.68% (Fig. 1B). Cervical cytology abnormalities were found in 7.53%, including ASC-US (5.41%), LSIL (0.79%), ASC-H (0.62%), HSIL (0.45%), SCC (0.19%), and AGC (0.06%) (Fig. 1C).

Age-wise analysis revealed escalating HPV infection rates (< 25 years: 17.62%, 25–65 years: 18.01%, > 65 years: 28.16%) (p < 0.001, Fig. 1D). Genotyping showed HPV-16 increased with age, HPV-18 varied, and others decreased (p = 0.021, Fig. 1E). The age-related distribution of cervical cytology indicated a consistent decline in the rates of NILM and HPV-negative results, accompanied by rising detection rates of various degrees of cervical lesions with increasing age, aligning with the trend observed for HPV-16 (p < 0.001, Fig. 1F).

Cervical Cancer Screening Patterns in Health Check-up Population

Among 43,102 health check-up patients (April 2017 - April 2022) (Table 2), hrHPV infection rate was 13.22% (Fig. 2A). Genotyping indicated an HPV-16 infection rate of 13.11%, HPV-18 at 4.95%, and others 12 types at 81.93% (Fig. 2B). Cervical cytology abnormalities were found in 3.88%, including ASC-US (3.06%), LSIL (0.66%), ASC-H (0.10%), HSIL (0.04%), SCC (0.01%), and AGC (0.02%) (Fig. 2C).

Age-wise analysis revealed highest HPV detection in < 25 years (24.71%), followed by > 65 years (17.56%), and lowest in 25–65 years (13.76%) (p < 0.001, Fig. 2D), exhibiting a U-shaped pattern. Genotyping results demonstrated a mild U-shaped trend in the detection rate of HPV-16 across different age groups. The detection rate of HPV-18 decreased with increasing age, while the detection rate of the other 12 types increased with age (p = 0.004, Fig. 2E). Cervical cytology-NILM displayed similar U-shaped patterns with age as HPV-negative results (p = 0.009, Fig. 2F).

Immediate Pathological Results of Patients Meeting the 1-Year Follow-up Requirement

Among the opportunistic screening population, 33,464 patients fulfilled the criteria for a 1-year follow-up assessment. Of the 2,176 patients under 25 years old, CIN3 + detection was found only in the HPV-positive NILM group, constituting 0.36% of cases. In the 25–65 years age group (30,697 patients), CIN3 + was detected in the HPV-negative LSIL group (1.13%), the HPV-positive NILM group (1.24%), and the group with a history of HPV-negative results but current HPV-positive ASC-US (2.13%). In 590 individuals over 65 years old, the HPV-positive NILM group exhibited 2.21% CIN3 + detection (Table 3).

In the health check-up population, 6,626 patients met the criteria for a 1-year follow-up evaluation. Among them, 149 were under 25 years old, 6,327 were aged 25–65 years, and 150 were over 65 years old. CIN3 + was found in the HPV-positive NILM group (0.59%) and the group with a history of HPV-negative results but current HPV-positive NILM (0.26%) within the 25–65 years age. No CIN3 + cases were identified in the < 25 years and > 65 years age groups (Table 4).

Pathological Results of 1-Year Follow-up Patients

Following the lapse of 1 year, 3,003 patients from the opportunistic screening population had available follow-up records. Among them, 117 were under 25 years old, 2,788 were aged 25–65 years, and 26 were over 65 years old. Only those aged 25–65 years in the HPV-positive NILM group showed a CIN3 + detection rate of 0.63%. No instances of CIN3 + were detected in the < 25 years and > 65 years age groups (Table 5).

Within the health check-up population, 1,101 patients possessed follow-up records after 1 year. Among them, 16 were under 25 years old, 1,070 were aged 25–65 years, and 15 were over 65 years old. Similarly, no CIN3 + cases were found in the < 25 years or > 65 years age group. Only the HPV-positive NILM group within the 25–65 years age group exhibited a CIN3 + detection rate of 0.14% (Table 6).

Immediate Pathological Results of Patients Meeting the 3-Year Follow-up Requirement

Within the opportunistic screening population, 6,350 patients satisfied the criteria for a 3-year follow-up. Among them, 235 were under 25 years old, 5,947 were aged 25–65 years, and 167 were over 65 years old. Notably, in the < 25 years and 25–65 years age groups, CIN3 + was detected in the HPV-negative ASC-US group at rates of 0.53% and 0.42%, respectively. No CIN3 + cases were found in the > 65 years age group (Table 7).

Within the regular health check-up population, 1,321 patients fulfilled the criteria for a 3-year follow-up. Among them, 16 were under 25 years old, 1,293 were aged 25–65 years, and 12 were over 65 years old. No occurrences of CIN3 + were identified in any of the age groups ( Table 8).

Pathological Results of 3-Year Follow-up Patients

Within the cohort of patients with a 3-year follow-up record, there were a total of 360 individuals in the opportunistic screening population and 36 individuals in the health check-up population. Among them, 13 individuals were under 25 years old and 346 individuals were aged 25–65 years in the outpatient population, while 1 individual was under 25 years old and 35 individuals were aged 25–65 years in the health check-up population. In > 65 years age group, only 1 was followed up in the outpatient population. Remarkably, no cases of CIN3 + were detected in any of the age groups examined, indicating favorable long-term outcomes (Tables 9 and 10).

In this study, we validated the occurrence rates of CIN3 + among individuals who met the 1-year and 3-year follow-up criteria recommended by the 2019 ASCCP guidelines (Fig. 3). By differentiating between opportunistic screening and health check-up groups, we observed favorable outcomes with the risk-based approach. Stratifying women based on previous screening results could enhance HPV-based screening's efficiency and effectiveness. This real-world evidence supports personalized screening strategies driven by individual risk levels, demonstrating its applicability in our region and similar middle-income nations.

It has been reported that HPV DNA testing, compared to cytological examination, can detect CIN3 + at an earlier stage and offer stronger preventive effects against invasive cervical cancer^8,13. This pivotal shift has prompted revisions in cervical cancer screening guidelines, with major nations spanning Europe, Australia, the Americas, and beyond now designating HPV testing as the primary diagnostic tool^14–20. However, studies have also found that global HPV infection rates vary by region and population^21,22。A meta-analysis of 194 global studies found that the HPV infection rate among women with normal cervical cytology is approximately 11.7% (95% CI: 11.6%-11.7%), with the highest rates observed in the Caribbean (35.4%), Eastern Africa (33.6%), and sub-Saharan Africa (24.0%)²³. These regional differences are related to the level of economic development, with more developed countries or regions having lower HPV infection rates. For example, in Europe and the US, HPV prevalence is typically 8–10%^23,24. Our data, in line with this global trend, reveal a significant hrHPV infection prevalence. The observed hrHPV positivity rates of 18.17% in opportunistic screening and 13.22% in health check-ups exceed the global average HPV infection rates and align with the characteristics of developing countries^25–27. The difference in infection rates between these two cohorts is primarily attributed to the demographics of each cohort. The outpatient cohort comprises individuals primarily seeking gynecological care due to symptoms or specific concerns, leading to opportunistic screening. This group may exhibit irregular screening patterns, driven by symptoms or episodic concerns. On the other hand, the health check-up cohort encompasses individuals undergoing routine general health examinations, where cervical cancer screening is part of preventive health measures, reflecting asymptomatic and routine health-seeking behavior. The elevated prevalence of overall HPV infection signifies a substantial risk associated with HPV infection within both demographics, shedding light on the imperfections in both vaccination coverage and screening practices, a concern pervasive particularly in developing nations². Furthermore, in the context where preventive HPV vaccination is not yet included in the national immunization program, cervical cancer screening remains a core component of cervical cancer prevention and control in China. The observed high positivity rates further underscore the urgent need for appropriate risk-based stratification to allocate resources effectively and target interventions.

While the principle of "equal risk, equal management" has been advocated as a criterion for further risk stratification and follow-up of individuals with hrHPV infection, the actual implementation can vary based on individual and regional contexts, lacking a standardized approach^28,29. Our study, along with the KPNC cohort, is among the few exploring follow-up after HPV-negative results^9,10. During the designated follow-up periods, CIN3 + cases were concentrated within specific risk groups. For instance, during the 1-year opportunistic screening, 2 CIN3 + cases were detected in the HPV-negative LSIL group out of 196, and 3-year follow-up found 19 CIN3 + cases in HPV-negative ASC-US group out of 6,304. Due to the gradual introduction of HPV vaccines in China starting in 2016 and limited supply, the individuals included in our study, conducted from 2012 to 2022, were primarily unvaccinated. As vaccination efforts spreads, non-HPV-related cervical cancer incidence might rise, highlighting the continued importance of cytological examinations and other effective risk stratification measures. Moreover, most CIN3 + cases were detected within HPV-positive cohorts, both in opportunistic screening (337 out of 28,150 cases) and health check-ups (27 out of 4,828 cases). Further age-based analysis revealed that the detection rates of CIN3 + varied within the equal-risk stratified cohorts: <25 years (0.32%), 25–65 years (1.05%), and > 65 years (2.05%). This highlights that the initial screening population might have been carrying the infection for a prolonged duration, with many cases being identified only when presenting at an older age. Remarkably, all CIN3 + cases identified in the health check-up cohort were within the 25–65 years age range, while none were found in the > 65 years range, underscoring the effectiveness of regular screening in timely disease control and prevention of disease progression. By stratifying ages 25–65, our study enriches screening strategy discussions, aiding efficiency and resource allocation^30,31.

The implementation of new strategies proposed for cervical cancer screening presents several challenges^7,32. Despite discouraging annual screenings for many years, practices persist. In the context of our study, many patients without timely follow-up results did not miss their appointments but actually arrived earlier than expected. This highlights the need to strike a balance in follow-up frequency, as excessive visits might potentially drain patients' patience and result in them not attending when necessary. On the other hand, the limited number of CIN3 + cases observed after the follow-up periods suggests low rapid progression risk, aligning with the disease's gradual development³³. As screening expands and vaccine coverage increases, cervical cancer incidence is expected to decline, raising the potential of extending screening intervals^25,34. Certainly, this must be approached with caution. Further research, including mathematical modeling and long-term studies, is necessary to evaluate the feasibility and safety of such an approach and provide evidence for potential guideline adjustments. The ultimately aiming is to achieve a balance between reducing the burden of frequent screenings and ensuring the continued effectiveness of cervical cancer prevention programs^35–37.

Our study's strengths are evident in its substantial sample size and extensive observation period, enhancing the robustness and real-world applicability of findings. Another significant aspect of our study is the validation conducted on both opportunistic screening and health check-up populations using commercial HPV testing and standardized protocols akin to developed regions. This validation extends to both groups endorsing the risk-based stratified management strategy, thereby emphasizing its adaptability across diverse healthcare settings.

However, it's crucial to acknowledge the study's limitations. Firstly, the data collection was confined to a single tertiary hospital in China, potentially constraining generalizability of our findings to broader region. Secondly, interpretation of absolute differences between distinct participant groups warrants caution. Moreover, limited follow-up data might restrict broader applicability, yet we maintain this limitation doesn't undermine overarching conclusions. We contend that while not meeting the rigorous standards of an ideal experiment, our study is well-suited for the context of initial screening, offering insights from a real-world dataset.

To conclude, our study seeks to bridge gaps in current screening practices and contribute to refining cervical cancer prevention and control efforts in China and globally. The risk-based stratified management strategy holds the potential to guide more precise interventions, reducing unnecessary procedures and enhancing the early detection of cervical cancer. The findings from this study have the potential to offer invaluable reference for countries facing similar resource constraints and to proffer insights shaping the evolution of more precise and efficacious cervical cancer screening policies worldwide.

Competing interests

The authors declare no conflict of interest.

Ethical Approval

This study was conducted in accordance with ethical guidelines and approved by the Institutional Review Board of Central South University Xiangya Hospital. The ethics committee waived the requirement of written informed consent for participation. The data used in this study were anonymized to ensure the privacy and confidentiality of the participants.

Authors' Contributions

Yu Zhang, Junxia Yan and Qihui Wu conceptualized and designed the study, conducted data analysis and interpretation. Qihui Wu drafted the manuscript. Peiyao Li and Fan Zhang collected and analyzed data. All authors reviewed and approved the final manuscript.

Data Sharing

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Funding

This work was supported by the National Key Research and Development Program of China (No. 2021YFC2701202), and the National Natural Science Foundation of China (No. U20A20368).

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.
Singh D, Vignat J, Lorenzoni V, et al. 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.
Zhang M, Zhong Y, Wang L, et al. Cervical Cancer Screening Coverage - China, 2018–2019. China CDC Wkly. 2022;4(48):1077–82.
Force USPST, Curry SJ, Krist AH, et al. Screening for Cervical Cancer: US Preventive Services Task Force Recommendation Statement. JAMA. 2018;320(7):674–86.
Saslow D, Solomon D, Lawson HW, et al. American Cancer Society, American Society for Colposcopy and Cervical Pathology, and American Society for Clinical Pathology screening guidelines for the prevention and early detection of cervical cancer. CA Cancer J Clin. 2012;62(3):147–72.
Perkins RB, Wentzensen N, Guido RS, Schiffman M. Cervical Cancer Screening: A Review. JAMA. 2023;330(6):547–58.
Zhang J, Zhao Y, Dai Y, et al. Effectiveness of High-risk Human Papillomavirus Testing for Cervical Cancer Screening in China: A Multicenter, Open-label, Randomized Clinical Trial. JAMA Oncol. 2021;7(2):263–70.
Melnikow J, Henderson JT, Burda BU, Senger CA, Durbin S, Weyrich MS. Screening for Cervical Cancer With High-Risk Human Papillomavirus Testing: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force. JAMA. 2018;320(7):687–705.
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.
Egemen D, Cheung LC, Chen X, et al. Risk Estimates Supporting the 2019 ASCCP Risk-Based Management Consensus Guidelines. J Low Genit Tract Dis. 2020;24(2):132–43.
Solomon D, Davey D, Kurman R, et al. The 2001 Bethesda System: terminology for reporting results of cervical cytology. JAMA. 2002;287(16):2114–9.
Mayr D, Schmoeckel E, Hohn AK, Hiller GGR, Horn LC. [Current WHO classification of the female genitals: Many new things, but also some old]. Pathologe. 2021;42(3):259–69.
Rebolj M, Rimmer J, Denton K, et al. Primary cervical screening with high risk human papillomavirus testing: observational study. BMJ. 2019;364:l240.
In: WHO guideline for screening and treatment of cervical pre-cancer lesions for cervical cancer prevention: Use of mRNA tests for human papillomavirus (HPV). 2nd ed. Geneva2021.
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(5):321–46.
Ciavattini A, Delli Carpini G, Giannella L, et al. European Federation for Colposcopy (EFC) and European Society of Gynaecological Oncology (ESGO) joint considerations about human papillomavirus (HPV) vaccination, screening programs, colposcopy, and surgery during and after the COVID-19 pandemic. Int J Gynecol Cancer. 2020;30(8):1097–100.
Hamers FF, Poullie AI, Arbyn M. Updated evidence-based recommendations for cervical cancer screening in France. Eur J Cancer Prev. 2022;31(3):279–86.
Hillemanns P, Friese K, Dannecker C, et al. Prevention of Cervical Cancer: Guideline of the DGGG and the DKG (S3 Level, AWMF Register Number 015/027OL, December 2017) - Part 1 with Introduction, Screening and the Pathology of Cervical Dysplasia. Geburtshilfe Frauenheilkd. 2019;79(2):148–59.
Bhatla N, Singhal S, Saraiya U, et al. Screening and management of preinvasive lesions of the cervix: Good clinical practice recommendations from the Federation of Obstetrics and Gynaecologic Societies of India (FOGSI). J Obstet Gynaecol Res. 2020;46(2):201–14.
Zeferino LC, Bastos JB, Vale D, et al. Guidelines for HPV-DNA Testing for Cervical Cancer Screening in Brazil. Rev Bras Ginecol Obstet. 2018;40(6):360–8.
Kombe Kombe AJ, Li B, Zahid A, et al. Epidemiology and Burden of Human Papillomavirus and Related Diseases, Molecular Pathogenesis, and Vaccine Evaluation. Front Public Health. 2020;8:552028.
Bruni L, Albero G, Serrano B, Mena M, Gómez D, Muñoz J, Bosch FX, dS S. Human papillomavirus and related diseases in the world. Summary Report. ICO/IARC Information Centre on HPV and Cencer (HPV Information Centre); 2019.
Bruni L, Diaz M, Castellsague X, Ferrer E, Bosch FX, de Sanjose S. Cervical human papillomavirus prevalence in 5 continents: meta-analysis of 1 million women with normal cytological findings. J Infect Dis. 2010;202(12):1789–99.
Grimes DR, Corry EMA, Malagon T, O'Riain C, Franco EL, Brennan DJ. Modeling Cervical Cancer Screening Strategies With Varying Levels of Human Papillomavirus Vaccination. JAMA Netw Open. 2021;4(6):e2115321.
Bao HL, Jin C, Wang S, et al. Prevalence of cervicovaginal human papillomavirus infection and genotypes in the pre-vaccine era in China: A nationwide population-based study. J Infect. 2021;82(4):75–83.
Maver PJ, Poljak M. Primary HPV-based cervical cancer screening in Europe: implementation status, challenges, and future plans. Clin Microbiol Infect. 2020;26(5):579–83.
Aitken CA, van Agt HME, Siebers AG, et al. Introduction of primary screening using high-risk HPV DNA detection in the Dutch cervical cancer screening programme: a population-based cohort study. BMC Med. 2019;17(1):228.
Kaufman HW, Alagia DP, Chen Z, Onisko A, Austin RM. Contributions of Liquid-Based (Papanicolaou) Cytology and Human Papillomavirus Testing in Cotesting for Detection of Cervical Cancer and Precancer in the United States. Am J Clin Pathol. 2020;154(4):510–6.
Wu Q, Zhao X, Fu Y, et al. A cross-sectional study on HPV testing with type 16/18 genotyping for cervical cancer screening in 11,064 Chinese women. Cancer Med. 2017;6(5):1091–101.
In: WHO guideline for screening and treatment of cervical pre-cancer lesions for cervical cancer prevention. 2nd ed. Geneva2021.
Zhao Y, Bao H, Ma L, et al. Real-world effectiveness of primary screening with high-risk human papillomavirus testing in the cervical cancer screening programme in China: a nationwide, population-based study. BMC Med. 2021;19(1):164.
Xia C, Hu S, Xu X, et al. Projections up to 2100 and a budget optimisation strategy towards cervical cancer elimination in China: a modelling study. Lancet Public Health. 2019;4(9):e462–72.
Cohen PA, Jhingran A, Oaknin A, Denny L. Cervical cancer. Lancet. 2019;393(10167):169–82.
Wang R, Pan W, Jin L, et al. Human papillomavirus vaccine against cervical cancer: Opportunity and challenge. Cancer Lett. 2020;471:88–102.
Rebolj M, Cuschieri K, Mathews CS, et al. Extension of cervical screening intervals with primary human papillomavirus testing: observational study of English screening pilot data. BMJ. 2022;377:e068776.
Kong L, Wang L, Wang Z, et al. DNA methylation for cervical cancer screening: a training set in China. Clin Epigenetics. 2020;12(1):91.
Li J, Wu R, Qu X, et al. Effectiveness and feasibility of self-sampling for human papillomavirus testing for internet-based cervical cancer screening. Front Public Health. 2022;10:938272.

Table 1 to 10 are available in the Supplementary Files section.

No competing interests reported.

PDF.pdf
Tables
1.png
Supplemental eFigure 1. Cervical Cancer Screening Results in Outpatient Population. (A) Pie chart depicting the number and proportion of individuals with positive and negative HPV results. (B) Pie chart showing the number and proportion of individuals with different hrHPV subtypes. (C) Pie chart illustrating the number and proportion of individuals diagnosed with various cytological abnormalities. (D) Line graph depicting the age distribution of HPV infections. (E) Age distribution line graph of hrHPV subtype distribution. (F) Age distribution line graph of cytological diagnosis distribution.
FIGURE012.png
Supplemental eFigure 2. Cervical Cancer Screening Results in Health Check-up Population. (A) Pie chart indicating the number and proportion of individuals with positive and negative HPV results. (B) Pie chart displaying the number and proportion of individuals with different hrHPV subtypes. (C) Pie chart presenting the number and proportion of individuals diagnosed with various cytological abnormalities. (D) Line graph illustrating the age distribution of HPV infections. (E) Age distribution line graph of hrHPV subtype distribution. (F) Age distribution line graph of cytological diagnosis distribution.

Download PDF

Reviewers agreed at journal
13 Nov, 2024
Reviewers agreed at journal
12 Nov, 2024
Reviewers invited by journal
17 Oct, 2024
Editor assigned by journal
11 Oct, 2024
Submission checks completed at journal
11 Oct, 2024
First submitted to journal
10 Oct, 2024

You are reading this latest preprint version

Assessment of a Risk-Based Stratified Management Strategy for Cervical Cancer Screening in Central China: A Real-World Study across Diverse Populations of 223,533 Opportunistic and 43,102 Health Check-up Participants Over a Decade

Status:

Version 1

Abstract

Figures

Introduction

Methods and Materials

Study Population

Cervical Cancer Screening Methods

HPV Testing

Cervical Cytology Examination

Pathological Follow-up

Statistical Analysis

Results

Cervical Cancer Screening Patterns in Outpatient Population

Cervical Cancer Screening Patterns in Health Check-up Population

Immediate Pathological Results of Patients Meeting the 1-Year Follow-up Requirement

Pathological Results of 1-Year Follow-up Patients

Immediate Pathological Results of Patients Meeting the 3-Year Follow-up Requirement

Pathological Results of 3-Year Follow-up Patients

Discussion

Declarations

References

Tables

Additional Declarations

Supplementary Files

Status:

Version 1