Effectiveness of high-risk human papillomavirus genotyping for cervical cancer screening. A multicentre screening cohort study in rural China

Authors

  • Yan-Qin Yu National Cancer Center /National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
  • Ming-Yue Jiang National Cancer Centre /National Clinical Research Centre for Cancer/Cancer Hospital. Chinese Academy of Medical Sciences and Peking Union Medical College. Department of Cancer Epidemiology. Beijing. China
  • Xun Zhang National Cancer Centre /National Clinical Research Centre for Cancer/Cancer Hospital. Chinese Academy of Medical Sciences and Peking Union Medical College. Department of Cancer Epidemiology. Beijing. China
  • Qin-Jing Pan National Cancer Centre /National Clinical Research Centre for Cancer/Cancer Hospital. Chinese Academy of Medical Sciences and Peking Union Medical College. Department of Cancer Epidemiology. Beijing. China
  • Le Dang National Cancer Centre /National Clinical Research Centre for Cancer/Cancer Hospital. Chinese Academy of Medical Sciences and Peking Union Medical College. Department of Cancer Epidemiology. Beijing. China
  • Rui-Mei Feng 2 National Cancer Centre /National Clinical Research Centre for Cancer/Cancer Hospital. Chinese Academy of Medical Sciences and Peking Union Medical College. Department of Cancer Epidemiology. Beijing. China
  • Naasra Mohamoud Ali First Affiliated Hospital of Dalian Medical University. Department of Oncology. Dalian. China
  • Wen Chen Baotou Medical College/Clinical Epidemiology Research Centre of The First Affiliated Hospital of Baotou Medical College. Department of Public Health and Preventive Medicine. Baotou. China
  • You-Lin Qiao National Cancer Centre /National Clinical Research Centre for Cancer/Cancer Hospital. Chinese Academy of Medical Sciences and Peking Union Medical College. Department of Cancer Epidemiology. Beijing. China

DOI:

https://doi.org/10.23938/ASSN.1065

Keywords:

Papillomavirus Infections, Uterine Cervical Neoplasms, Mass Screening, Rural Areas, China

Abstract

Background. This study aimed to assess the effectiveness of high-risk human papillomavirus (HR-HPV) primary testing for cervical cancer screening in China’s rural areas.

Methods. Women aged 21-64 years were recruited. Cervical cytology was diagnosed following the Bethesda 2001 classification system, HPV infection (HR-HPV, HPV-16, HPV-18, and other 12 genotypes) identified by Cobas-4800, and colposcopy and biopsy performed when required. Primary outcomes were defined as the cumulative incidence of cervical intraepithelial neoplasia grade 2/3/higher (CIN2/3+) and its relative risk at baseline and at the 36-month follow-up.

Results. The study included 9,218 women; mean age was 45.15 years (SD: 8.74); 81% completed the follow-up. The most frequent type of cytological lesions (12.4% ) were ASCUS (8.4%) and LSIL (2.2%). HR-HPV infection (16.3%) was more prevalent in HPV-16 than in HPV-18 (3 vs 1.5%); a positive relationship with the severity of the lesions, from 29.8% in ASCUS to 89.6% in HSIL was found. At baseline, 3.5% of the patients underwent colposcopy; 20% had a positive diagnosis. At the 36-month follow-up, the cumulative incidences of CIN2+ and CIN3+ were higher in women with HR-HPV infection (16.9 vs 0.5% and 8.2 vs 0.2%). The relative risk of CIN2/3+ was lower in HR-HPV-negative women compared to those with a negative cytology at baseline (0.4; 95%CI: 0.3–0.4).

Conclusions. High-risk HPV-based screening may significantly reduce the risk of CIN2/3+ compared with cytology testing. This may be a new resource for public health demands in China’s rural areas.

Downloads

Download data is not yet available.

Author Biographies

Yan-Qin Yu , National Cancer Center /National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College

1 Baotou Medical College/Clinical Epidemiology Research Centre of The First Affiliated Hospital of Baotou Medical College. Department of Public Health and Preventive Medicine. Baotou. China

2 National Cancer Centre /National Clinical Research Centre for Cancer/Cancer Hospital. Chinese Academy of Medical Sciences and Peking Union Medical College. Department of Cancer Epidemiology. Beijing. China

Ming-Yue Jiang , National Cancer Centre /National Clinical Research Centre for Cancer/Cancer Hospital. Chinese Academy of Medical Sciences and Peking Union Medical College. Department of Cancer Epidemiology. Beijing. China

2 National Cancer Centre /National Clinical Research Centre for Cancer/Cancer Hospital. Chinese Academy of Medical Sciences and Peking Union Medical College. Department of Cancer Epidemiology. Beijing. China

Xun Zhang , National Cancer Centre /National Clinical Research Centre for Cancer/Cancer Hospital. Chinese Academy of Medical Sciences and Peking Union Medical College. Department of Cancer Epidemiology. Beijing. China

2 National Cancer Centre /National Clinical Research Centre for Cancer/Cancer Hospital. Chinese Academy of Medical Sciences and Peking Union Medical College. Department of Cancer Epidemiology. Beijing. China

Qin-Jing Pan , National Cancer Centre /National Clinical Research Centre for Cancer/Cancer Hospital. Chinese Academy of Medical Sciences and Peking Union Medical College. Department of Cancer Epidemiology. Beijing. China

2 National Cancer Centre /National Clinical Research Centre for Cancer/Cancer Hospital. Chinese Academy of Medical Sciences and Peking Union Medical College. Department of Cancer Epidemiology. Beijing. China

Le Dang , National Cancer Centre /National Clinical Research Centre for Cancer/Cancer Hospital. Chinese Academy of Medical Sciences and Peking Union Medical College. Department of Cancer Epidemiology. Beijing. China

2 National Cancer Centre /National Clinical Research Centre for Cancer/Cancer Hospital. Chinese Academy of Medical Sciences and Peking Union Medical College. Department of Cancer Epidemiology. Beijing. China

Rui-Mei Feng , 2 National Cancer Centre /National Clinical Research Centre for Cancer/Cancer Hospital. Chinese Academy of Medical Sciences and Peking Union Medical College. Department of Cancer Epidemiology. Beijing. China

2 National Cancer Centre /National Clinical Research Centre for Cancer/Cancer Hospital. Chinese Academy of Medical Sciences and Peking Union Medical College. Department of Cancer Epidemiology. Beijing. China

Naasra Mohamoud Ali , First Affiliated Hospital of Dalian Medical University. Department of Oncology. Dalian. China

3 First Affiliated Hospital of Dalian Medical University. Department of Oncology. Dalian. China

Wen Chen , Baotou Medical College/Clinical Epidemiology Research Centre of The First Affiliated Hospital of Baotou Medical College. Department of Public Health and Preventive Medicine. Baotou. China

1 Baotou Medical College/Clinical Epidemiology Research Centre of The First Affiliated Hospital of Baotou Medical College. Department of Public Health and Preventive Medicine. Baotou. China

You-Lin Qiao , National Cancer Centre /National Clinical Research Centre for Cancer/Cancer Hospital. Chinese Academy of Medical Sciences and Peking Union Medical College. Department of Cancer Epidemiology. Beijing. China

2 National Cancer Centre /National Clinical Research Centre for Cancer/Cancer Hospital. Chinese Academy of Medical Sciences and Peking Union Medical College. Department of Cancer Epidemiology. Beijing. China

4 School of Population Medicine and Public Health. Chinese Academy of Medical Sciences and Peking Union Medical College. Beijing. China

References

SUNG H, FERLAY J, SIEGEL RL, LAVERSANNE M, SOERJOMATARAM I, JEMAL A 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): 209-249. https://doi.org/10.3322/caac.21660

XIA C, DONG X, LI H, CAO M, SUN D, HE S et al. Cancer statistics in China and United States, 2022: profiles, trends, and determinants. Chin Med J (Engl) 2022; 135(5): 584-590. https://doi.org/10.1097/CM9.0000000000002108

TERASAWA T, HOSONO S, SASAKI S, HOSHI K, HAMASHIMA Y, KATAYAMA T et al. Comparative accuracy of cervical cancer screening strategies in healthy asymptomatic women: a systematic review and network meta-analysis. Sci Rep 2022; 12(1): 94. https://doi.org/10.1038/s41598-021-04201-y

BONDE JH, SANDRI MT, GARY DS, ANDREWS JC. Clinical utility of human papillomavirus genotyping in cervical cancer screening: a systematic review. J Low Genit Tract Dis 2020; 24(1): 1-13. https://doi.org/10.1097/LGT.0000000000000494

BUCCHI L, BALDACCHINI F, MANCINI S, RAVAIOLI A, GIULIANI O, VATTIATO R et al. Estimating the impact of an organised screening programme on cervical cancer incidence: a 26-year study from northern Italy. Int J Cancer. 2019; 144(5): 1017-1026. https://doi.org/10.1002/ijc.31806

BAO HL, FANG LW, WANG LH. Current situation and strategic thinking of establishing cervical cancer prevention and control system in the world. Chinese Journal of Preventive Medicine 2017; 51 (1): 96-100.

ZHAO YQ, DAI Y, DANG L, KONG LH, ZHANG Y, FENG RM et al. [Real-world research on cervical cancer screening program and effect evaluation for Chinese population]. Zhonghua Zhong Liu Za Zhi. 2018; 40(10): 764-771. https://doi.org/10.3760/cma.j.issn.0253-3766.2018.10.008

CHUA BWB, MA VY, ALCÁNTAR-FERNÁNDEZ J, WEE HL. Is it time to genotype beyond HPV16 and HPV18 for cervical cancer screening? Int J Public Health 2022; 67: 1604621. https://doi.org/10.3389/ijph.2022.1604621

CASTLE PE, STOLER MH, WRIGHT TC JR, SHARMA A, WRIGHT TL, BEHRENS CM. 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(9): 880-890. https://doi.org/10.1016/S1470-2045(11)70188-7

ZHAO YX, MA L, REN WH, SONG B, WANG LH, DI JL, WU JL. Analysis of the reported data of national cervical cancer screening program in rural areas in China from 2009 to 2018. Zhonghua Yi Xue Za Zhi 2021; 101: 1863-1868. doi:10.3760/cma.j.cn112137-20210111-00075

OGILVIE GS, VAN NIEKERK D, KRAJDEN M, SMITH LW, COOK D, GONDARA L et al. Effect of screening with primary cervical HPV testing vs cytology testing on high-grade cervical intraepithelial neoplasia at 48 months: the HPV FOCAL randomized clinical trial. JAMA 2018; 320(1): 43-52. https://doi.org/10.1001/jama.2018.7464

SMITH MA, SHERRAH M, SULTANA F, CASTLE PE, ARBYN M, GERTIG D et al. National experience in the first two years of primary human papillomavirus (HPV) cervical screening in an HPV vaccinated population in Australia: observational study. BMJ 2022; 376: e068582. https://doi.org/10.1136/bmj-2021-068582

DEL MISTRO A, ADCOCK R, CAROZZI F, GILLIO-TOS A, DE MARCO L, GIRLANDO S et al. Human papilloma virus genotyping for the cross-sectional and longitudinal probability of developing cervical intraepithelial neoplasia grade 2 or more. Int J Cancer 2018; 143(2): 333-342. https://doi.org/10.1002/ijc.31326

KUROKAWA T, YOSHIDA Y, IWANARI O, OISHI T, KASAI T, HAMADA M et al. Implementation of primary HPV testing in Japan. Mol Clin Oncol 2020; 13(4): 22. https://doi.org/10.3892/mco.2020.2092

ELFSTRÖM KM, EKLUND C, LAMIN H, ÖHMAN D, HORTLUND M, ELFGREN K et al. Organized primary human papillomavirus-based cervical screening: A randomized healthcare policy trial. PLoS Med 2021; 18(8): e1003748. https://doi.org/10.1371/journal.pmed.1003748

BEDELL SL, GOLDSTEIN LS, GOLDSTEIN AR, GOLDSTEIN AT. Cervical cancer screening: past, present, and future. Sex Med Rev 2020; 8(1): 28-37. https://doi.org/10.1016/j.sxmr.2019.09.005

ZHANG J, ZHAO Y, DAI Y, DANG L, MA L, YANG C 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): 263-270. https://doi.org/10.1001/jamaoncol.2020.6575

WANG H L, YANG X, LI Y B, YU H, FEI XD. Application of standardized patients in job training of rural obstetrician and gynecologists. China Health Industry 2011; 8(34): 129-130. https://doi.org/10.16659/j.cnki.1672-5654.2011.34.016

ZHU T. The clinical value of TCT and HPV examination combined with colposcopy for cervical cancer screening. Shenzhen Journal of Integrated Traditional Chinese and Western Medicine 2020; 30(17): 72-73. https://doi.org/10.16458/j.cnki.1007-0893.2020.17.036

ZHAO J. [The results of cervical cancer screening among 16408 rural women in Gujiao city were analyzed by different detection methods]. Chinese Drug and Clinical 2021; 21(09): 1596-1598. https://doi.org/10.11655/zgywylc2021.09.068

WANG Y, WANG D, YEERJIANG KAYM, TALEHATI DDE, CHI Y, LIU L et al. Screening effect of self-sampling HPV detection as an alternative to cervical cancer screening in areas lacking health resources in Xinjiang. Advances in Modern Obstetrics and Gynecology 2023; 32(02): 90-94.

LIAN W, SU X. Effect of positive fluid-based cytology on screening for cervical lesions. Journal of Chronic Diseases 2023; 24(01): 65-67. https://doi.org/10.16440/J.CNKI.1674-8166.2023.01.17

CANFELL K, SAVILLE M, CARUANA M, GEBSKI V, DARLINGTON-BROWN J, BROTHERTON J et al. Protocol for compass: a randomised controlled trial of primary HPV testing versus cytology screening for cervical cancer in HPV-unvaccinated and vaccinated women aged 25-69 years living in Australia. BMJ Open 2018; 8(1): e016700. https://doi.org/10.1136/bmjopen-2017-016700

XUE P, GAO LL, YIN J, HAN LL, ZHAO J, LI L et al. A direct comparison of four high-risk human papillomavirus tests versus the cobas test: detecting CIN2+ in low-resource settings. J Med Virol 2019; 91(7): 1342-1350. https://doi.org/10.1002/jmv.25451

CHRYSOSTOMOU AC, KOSTRIKIS LG. Methodologies of primary HPV testing currently applied for cervical cancer screening. Life (Basel) 2020; 10(11): 290. https://doi.org/10.3390/life10110290

YANG L, LIU D, WANG F. Application of fluid-based cytology combined with colposcopy in cervical cancer screening. Journal of North Sichuan Medical College 2023; 38(02): 262-264.

ZHAO S, CHEN H, ZHAO FH. [Global guidelines for cervical cancer and precancerous lesions treatment: a systematic review]. Zhonghua Yi Xue Za Zhi 2022; 102(22): 1666-1676. https://doi.org/10.3760/cma.j.cn112137-20211106-02466

KOMBE KOMBE AJ, LI B, ZAHID A, MENGIST HM, BOUNDA GA et al. Epidemiology and burden of human papillomavirus and related diseases, molecular pathogenesis, and vaccine evaluation. Front Public Health 2021; 8: 552028. https://doi.org/10.3389/fpubh.2020.552028

LIU L, WANG D, DONG H, JIN C, JIANG L, SONG H et al. Characteristics of carcinogenic HPV genotypes in north China plain and the association with cervical lesions. Medicine (Baltimore) 2019; 98(37): e17087. https://doi.org/10.1097/MD.0000000000017087

GILHAM C, SARGENT A, KITCHENER HC, PETO J. HPV testing compared with routine cytology in cervical screening: long-term follow-up of ARTISTIC RCT. Health Technol Assess 2019; 23(28): 1-44. https://doi.org/10.3310/hta23280

ŞAHIN D, KOÇ N, AKBAŞ M. Effects of an additional liquid based cytology prepate on cytological diagnosis in high-risk HPV positive, PaP Test Negative Cases. Sisli Etfal Hastan Tip Bul 2019; 53(4): 361-365. https://doi.org/10.14744/SEMB.2019.23434

ZHONG G, WANG Y, XIE Q, LIN R, YAO T. HPV-specific risk assessment of cervical cytological abnormalities. BMC Cancer 2021; 21(1): 949. https://doi.org/10.1186/s12885-021-08703-w

YANG H, LI SP, CHEN Q, MORGAN C. Barriers to cervical cancer screening among rural women in eastern China: a qualitative study. BMJ Open 2019; 9(3): e026413. https://doi.org/10.1136/bmjopen-2018-026413

ZHAO Y, ZHAO F, HU S, CHEN W, CHEN F, CUI J et al. [Multi-center cross-sectional study on type-specific human papillomavirus infection among Chinese women]. Zhonghua Liu Xing Bing Xue Za Zhi 2015; 36(12): 1351-1356.

ZHANG J, CHENG K, WANG Z. Prevalence and distribution of human papillomavirus genotypes in cervical intraepithelial neoplasia in China: a meta-analysis. Arch Gynecol Obstet 2020; 302(6): 1329-1337. https://doi.org/10.1007/s00404-020-05787-w

YAN X, HUANG Y, ZHANG M, HU X, LI K, JING M. Prevalence of human papillomavirus infection and type distribution among Uyghur females in Xinjiang, northwest China. Oncol Lett 2020; 20(4): 25. https://doi.org/10.3892/ol.2020.11886

PETRY KU, COX JT, JOHNSON K, QUINT W, RIDDER R, SIDERI M et al. Evaluating HPV-negative CIN2+ in the ATHENA trial. Int J Cancer 2016; 138(12): 2932-2939. https://doi.org/10.1002/ijc.30032

STOLER MH, WRIGHT TC JR, PARVU V, VAUGHAN L, YANSON K, ECKERT K et al. The onclarity human papillomavirus trial: design, methods, and baseline results. Gynecol Oncol 2018; 149(3): 498-505. https://doi.org/10.1016/j.ygyno.2018.04.007

WANG Z, LI Z, LI J, WANG C, WANG W, HAO M et al. Prevalence and distribution of HPV genotypes in 1387 women with cervical intraepithelial neoplasia 2/3 in Shanxi province, China. J Cancer 2018; 9(16): 2802-2806. https://doi.org/10.7150/jca.25614

FENG RM, WANG M, SMITH JS, DONG L, CHEN F, PAN QJ et al. Risk of high-risk human papillomavirus infection and cervical precancerous lesions with past or current trichomonas infection: a pooled analysis of 25,054 women in rural China. J Clin Virol 2018; 99-100: 84-90. https://doi.org/10.1016/j.jcv.2017.12.015

ST-MARTIN G, THAMSBORG LH, ANDERSEN B, CHRISTENSEN J, EJERSBO D, JOCHUMSEN K et al. Management of low-grade cervical cytology in young women. Cohort study from Denmark. Acta Oncol 2021; 60(4): 444-451. https://doi.org/10.1080/0284186X.2020.1831061

WOODMAN CB, COLLINS S, WINTER H, BAILEY A, ELLIS J, PRIOR P et al. Natural history of cervical human papillomavirus infection in young women: a longitudinal cohort study. Lancet 2001; 357(9271): 1831-1836. https://doi.org/10.1016/S0140-6736(00)04956-4

CHEUNG LC, EGEMEN D, CHEN X, KATKI HA, DEMARCO M, WISER AL et al. 2019 ASCCP risk-based management consensus guidelines: methods for risk estimation, recommended management, and validation. J Low Genit Tract Dis 2020; 24(2): 90-101. https://doi.org/10.1097/LGT.0000000000000528

DEMARCO M, EGEMEN D, RAINE-BENNETT TR, CHEUNG LC, BEFANO B, POITRAS NE et al. A study of partial human papillomavirus genotyping in support of the 2019 ASCCP Risk-Based Management Consensus Guidelines. J Low Genit Tract Dis 2020; 24(2): 144-147. https://doi.org/10.1097/LGT.0000000000000530

SHI JF, BELINSON JL, ZHAO FH, PRETORIUS RG, LI J, MA JF et al. Human papillomavirus testing for cervical cancer screening: results from a 6-year prospective study in rural China. Am J Epidemiol 2009; 170(6): 708-716. https://doi.org/10.1093/aje/kwp188

SCHIFFMAN M, KINNEY WK, CHEUNG LC, GAGE JC, FETTERMAN B, POITRAS NE et al. Relative performance of HPV and cytology components of cotesting in cervical screening. J Natl Cancer Inst. 2018; 110(5): 501-508. https://doi.org/10.1093/jnci/djx225

Published

2024-05-31

How to Cite

Yu, Y.-Q., Jiang, M.-Y. ., Zhang, X., Pan, Q.-J., Dang, L., Feng, R.-M., Ali, N. M., Chen, W., & Qiao, Y.-L. (2024). Effectiveness of high-risk human papillomavirus genotyping for cervical cancer screening. A multicentre screening cohort study in rural China. Anales Del Sistema Sanitario De Navarra, 47(2), e1065. https://doi.org/10.23938/ASSN.1065

Issue

Section

Research articles