Cancer Causes & Control

, Volume 29, Issue 3, pp 297–304 | Cite as

A risk prediction model to allow personalized screening for cervical cancer

  • Michael B. Rothberg
  • Bo Hu
  • Laura Lipold
  • Sarah Schramm
  • Xian Wen Jin
  • Andrea Sikon
  • Glen B. Taksler
Original paper



Cervical cancer screening guidelines are in evolution. Current guidelines do not differentiate recommendations based on individual patient risk.


To derive and validate a tool for predicting individualized probability of cervical intraepithelial neoplasia grade 2 or higher (CIN2+) at a single time point, based on demographic factors and medical history.


The study design consisted of an observational cohort with hierarchical generalized linear regression modeling.


The study was conducted in a setting of 33 primary care practices from 2004 to 2010.


The participants of the study were women aged ≥ 30 years.

Main outcome and measures

CIN2+ was the main outcome on biopsy, and the following predictors were included: age, race, marital status, insurance type, smoking history, median income based on zip code, prior human papilloma virus (HPV) results.


The final dataset included 99,319 women. Of these, 745 (0.75%) had CIN2+. The multivariable model had a C-statistic of 0.81. All factors but race were independently associated with CIN2+. The model categorized women as having below-average CIN2+ risk (0.15% predicted vs. 0.12% observed risk), average CIN2+ risk (0.42% predicted vs. 0.36% observed), and above-average CIN2+ risk (1.76% predicted vs. 1.85% observed). Before screening, women at below-average risk had a risk of CIN2+ well below that of women with ASCUS and HPV negative (0.12 vs. 0.20%).

Conclusions and relevance

A multivariable model using data from the electronic health record was able to stratify women across a 50-fold gradient of risk for CIN2+. After further validation, use of a similar model could enable more targeted cervical cancer screening.


Cervical cancer Screening Guidelines 

Supplementary material

10552_2018_1013_MOESM1_ESM.doc (1.2 mb)
Supplementary material 1 (DOC 1231 KB)


  1. 1.
    Gustafsson L, Ponten J, Zack M, Adami HO (1997) International incidence rates of invasive cervical cancer after introduction of cytological screening. Cancer Causes Control 8(5):755–763CrossRefPubMedGoogle Scholar
  2. 2.
    Walboomers JM, Jacobs MV, Manos MM et al (1999) Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol 189(1):12–19CrossRefPubMedGoogle Scholar
  3. 3.
    Arbyn M, Roelens J, Simoens C et al (2013) Human papillomavirus testing versus repeat cytology for triage of minor cytological cervical lesions. Cochrane Database Syst Rev 3:CD008054Google Scholar
  4. 4.
    Saslow D, Solomon D, Lawson HW et al (2012) 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. Am J Clin Pathol 137(4):516–542CrossRefPubMedGoogle Scholar
  5. 5.
    Dijkstra MG, van Zummeren M, Rozendaal L et al (2016) Safety of extending screening intervals beyond five years in cervical screening programmes with testing for high risk human papillomavirus: 14 year follow-up of population based randomised cohort in the Netherlands. BMJ 355:i4924CrossRefPubMedGoogle Scholar
  6. 6.
    Vesco KK, Whitlock EP, Eder M, Burda BU, Senger CA, Lutz K (2011) Risk factors and other epidemiologic considerations for cervical cancer screening: a narrative review for the U.S. Preventive Services Task Force. Ann Intern Med 155(10):698–705CrossRefPubMedGoogle Scholar
  7. 7.
    Masur H, Brooks JT, Benson CA, Holmes KK, Pau AK, Kaplan JE (2014) Prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: Updated Guidelines from the Centers for Disease Control and Prevention, National Institutes of Health, and HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis 58(9):1308–1311CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Wright TC Jr, Massad LS, Dunton CJ et al (2007) 2006 consensus guidelines for the management of women with cervical intraepithelial neoplasia or adenocarcinoma in situ. J Low Genit Tract Dis 11(4):223–239CrossRefPubMedGoogle Scholar
  9. 9.
    McCredie MR, Sharples KJ, Paul C et al (2008) Natural history of cervical neoplasia and risk of invasive cancer in women with cervical intraepithelial neoplasia 3: a retrospective cohort study. Lancet Oncol 9(5):425–434CrossRefPubMedGoogle Scholar
  10. 10.
    Steyerberg EW, Harrell FE Jr, Borsboom GJ, Eijkemans MJ, Vergouwe Y, Habbema JD (2001) Internal validation of predictive models: efficiency of some procedures for logistic regression analysis. J Clin Epidemiol 54(8):774–781CrossRefPubMedGoogle Scholar
  11. 11.
    Castle PE, Sideri M, Jeronimo J, Solomon D, Schiffman M (2007) Risk assessment to guide the prevention of cervical cancer. Am J Obstet Gynecol 197(4):e351–e356CrossRefGoogle Scholar
  12. 12.
    International Collaboration of Epidemiological Studies of Cervical Cancer (2007) Comparison of risk factors for invasive squamous cell carcinoma and adenocarcinoma of the cervix: collaborative reanalysis of individual data on 8,097 women with squamous cell carcinoma and 1,374 women with adenocarcinoma from 12 epidemiological studies. Int J Cancer 120(4):885–891CrossRefGoogle Scholar
  13. 13.
    Appleby P, Beral V, de Gonzalez AB et al (2006) Carcinoma of the cervix and tobacco smoking: collaborative reanalysis of individual data on 13,541 women with carcinoma of the cervix and 23,017 women without carcinoma of the cervix from 23 epidemiological studies. Int J Cancer 118(6):1481–1495CrossRefPubMedGoogle Scholar
  14. 14.
    Plummer M, Herrero R, Franceschi S et al (2003) Smoking and cervical cancer: pooled analysis of the IARC multi-centric case–control study. Cancer Causes Control 14(9):805–814CrossRefPubMedGoogle Scholar
  15. 15.
    International Collaboration of Epidemiological Studies of Cervical Cancer (2009) Cervical carcinoma and sexual behavior: collaborative reanalysis of individual data on 15,461 women with cervical carcinoma and 29,164 women without cervical carcinoma from 21 epidemiological studies. Cancer Epidemiol Biomark Prev 18(4):1060–1069CrossRefGoogle Scholar
  16. 16.
    Cotton SC, Sharp L, Seth R et al (2007) Lifestyle and socio-demographic factors associated with high-risk HPV infection in UK women. Br J Cancer 97(1):133–139CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Castellsague X, Diaz M, de Sanjose S et al (2006) Worldwide human papillomavirus etiology of cervical adenocarcinoma and its cofactors: implications for screening and prevention. J Natl Cancer Inst 98(5):303–315CrossRefPubMedGoogle Scholar
  18. 18.
    Munoz N, Bosch FX, de Sanjose S et al (2003) Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med 348(6):518–527CrossRefPubMedGoogle Scholar
  19. 19.
    Al Rowas S, Rothberg MB, Johnson B et al (2017) The association between insurance type and cost-related delay in care: a survey. Am J Manag Care 23(7):435–442PubMedGoogle Scholar
  20. 20.
    Charlton BM, Carwile JL, Michels KB, Feldman S (2013) A cervical abnormality risk prediction model: can we use clinical information to predict which patients with ASCUS/LSIL Pap tests will develop CIN 2/3 or AIS? J Low Genit Tract Dis 17(3):242–247CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Austin RM, Onisko A, Druzdzel MJ (2010) The Pittsburgh cervical cancer screening model: a risk assessment tool. Arch Pathol Lab Med 134(5):744–750PubMedGoogle Scholar
  22. 22.
    Saini SD, van Hees F, Vijan S (2014) Smarter screening for cancer: possibilities and challenges of personalization. JAMA 312(21):2211–2212CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Katki HA, Schiffman M, Castle PE et al (2013) Benchmarking CIN3+ risk as the basis for incorporating HPV and Pap cotesting into cervical screening and management guidelines. J Low Genit Tract Dis 17(5 Suppl 1):S28–S35CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Jeronimo J, Castle PE, Temin S, Shastri SS (2016) Secondary prevention of cervical cancer: American Society of Clinical Oncology resource-stratified clinical practice guideline summary. J Oncol Pract 13:129–133CrossRefPubMedGoogle Scholar
  25. 25.
    Kim JJ, Burger EA, Sy S, Campos NG (2017) Optimal cervical cancer screening in women vaccinated against human papillomavirus. J Natl Cancer Inst 109(2):djw216CrossRefPubMedGoogle Scholar
  26. 26.
    Braun V, Gavey N (1999) With the best of reasons’: cervical cancer prevention policy and the suppression of sexual risk factor information. Soc Sci Med 48(10):1463–1474CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Michael B. Rothberg
    • 1
    • 2
  • Bo Hu
    • 3
  • Laura Lipold
    • 4
  • Sarah Schramm
    • 2
  • Xian Wen Jin
    • 1
  • Andrea Sikon
    • 1
  • Glen B. Taksler
    • 2
  1. 1.Department of Internal Medicine, Medicine InstituteCleveland ClinicClevelandUSA
  2. 2.Center for Value-Based Care Research, Medicine InstituteCleveland ClinicClevelandUSA
  3. 3.Quantitative Health Sciences InstituteCleveland ClinicClevelandUSA
  4. 4.Department of Family Medicine, Medicine InstituteCleveland ClinicClevelandUSA

Personalised recommendations