Cytology and HPV Testing in Primary Cervical Cancer Screening

  • Satinder Kaur
  • Shilpa Jamwal


Cervical cancer is the only female genital tract cancer which can be diagnosed and treated in precancerous state by simple screening techniques. The incidence of the disease has come down drastically in countries which have successfully implemented the screening programmes. Cytology, visual inspection with acetic acid, visual inspection with Lugol’s iodine and various HPV diagnostic tests have been used alone or in sequencing for screening. With the advent of newer diagnostics tests with better sensitivity and specificity, it has been possible to triage patients more effectively. This has also helped in increasing the screening interval leading to better compliance. Cytology and HPV testing are the two main methods which are universally adopted for primary screening of cervical cancer.


HPV Pap smear Cytology Liquid-based cytology HPV tests Hybrid capture Care HPV Cervical cancer screening 


  1. 1.
    Papanicolaou GN. New cancer diagnosis. In: Proceedings third race betterment conference. Battle Creek, MI: Race Betterment Foundation; 1928. p. 528–34.Google Scholar
  2. 2.
    Papanicolaou GN. Atlas of exfoliative cytology. Boston: Commonwealth Fund University Press; 1954.Google Scholar
  3. 3.
    Reagan JW, Seidemann IL, Sarcusa Y. Cellular morphology of carcinoma in situ and dysplasia or atypical hyperplasia of uterine cervix. Cancer. 1953;6:224–35.CrossRefGoogle Scholar
  4. 4.
    Richart RM. Natural history of cervical intraepithelial neoplasia. Clin Obstet Gynecol. 1968;10:748–84.CrossRefGoogle Scholar
  5. 5.
    National Cancer Workshop. The 1988 Bethesda system for reporting cervical/vaginal cytologic diagnosis. JAMA. 1989;262:931–4.CrossRefGoogle Scholar
  6. 6.
    Fahey MT, Irwig L, Macaskill P. Meta-analysis of Pap test accuracy. Am J Epidemiol. 1995;14:680–9.CrossRefGoogle Scholar
  7. 7.
    Hartmann K, Hall SA, Nanda K, et al. Systematic evidence review number 25: screening for cervical cancer. Rockville: US Department of Health and Human Services; 2002.Google Scholar
  8. 8.
    Clavel C, Masure M, Bory JP, et al. Human papillomavirus testing in primary screening for the detection of high-grade cervical lesions: a study of 7932 women. Br J Cancer. 2001;84:1616–23.CrossRefGoogle Scholar
  9. 9.
    Hutchinson ML, Zahniser DJ, Sherman ME, et al. Utility of liquid-based cytology for cervical carcinoma screening: results of a population-based study conducted in a region of Costa Rica with a high incidence of cervical carcinoma. Cancer. 1999;87:48–55.CrossRefGoogle Scholar
  10. 10.
    Lee KR, Ashfaq R, Birdson GG, et al. Comparison of conventional Papanicolaou smears and a fluid-based, thin-layer system for cervical cancer screening. Obstet Gynecol. 1997;90:278–84.CrossRefGoogle Scholar
  11. 11.
    Marino JF, Fremont-Smith M. Direct-to-vial experience with Auto Cyte PREP in a small New England regional cytology practice. J Reprod Med. 2001;46:353–8.PubMedGoogle Scholar
  12. 12.
    Eversole GM, Moriarty AT, Schwartz MR, et al. Practices of participants in the College of American Pathologists interlaboratory comparison program in cervicovaginal cytology, 2006. Arch Pathol Lab Med. 2010;134:331–5.PubMedGoogle Scholar
  13. 13.
    Arbyn M, Bergeron C, Klinkhamer P, et al. Liquid compared with conventional cervical cytology: a systemic review and meta-analysis. Obstet Gynecol. 2008;111:167–77.CrossRefGoogle Scholar
  14. 14.
    Boulet GA, Horvath CA, Berghmans S, Bogers J. Human papillomavirus in cervical cancer screening: important role as biomarker. Cancer Epidemiol Biomarkers Prev. 2008;17:810–7.CrossRefGoogle Scholar
  15. 15.
    Wheeler CM, Hunt WC, Schiffman M, Castle PE, Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesions Triage Study Group. Human papillomavirus genotypes and the cumulative 2-year risk of cervical precancer. J Infect Dis. 2006;194:1291–9.CrossRefGoogle Scholar
  16. 16.
    Ungar E, Budgeon LR, Myerson D, et al. Viral diagnosis by in situ hybridization. Am J Surg Pathol. 1986;10:1–8.CrossRefGoogle Scholar
  17. 17.
    Cubie HA, Norval M. Detection of human papillomaviruses in paraffin wax sections with biotinylated synthetic oligonucleotide probes and immunogold staining. J Clin Pathol. 1989;42:988–91.CrossRefGoogle Scholar
  18. 18.
    Coutlée F, Mayrand MH, Provencher D, Franco E. The future of HPV testing in clinical laboratories and applied virology research. Clin Diagn Virol. 1997;8:123–41.CrossRefGoogle Scholar
  19. 19.
    Qiao YL, Sellors JW, Eder PS, et al. A new HPV-DNA test for cervical-cancer screening in developing regions: a cross-sectional study of clinical accuracy in rural China. Lancet Oncol. 2008;9(10):929–36.CrossRefGoogle Scholar
  20. 20.
    Gravitt PE, Schiffman M, Solomon D, Wheeler CM, Castle PE. A comparison of linear array and hybrid capture 2 for detection of carcinogenic human papillomavirus and cervical precancer in ASCUS-LSIL triage study. Cancer Epidemiol Biomarkers Prev. 2008;17:1248–54.CrossRefGoogle Scholar
  21. 21.
    Heideman DA, Hesselink AT, Berkhof J, et al. Clinical validation of the cobas® 4800 HPV Test for cervical screening purposes. J Clin Microbiol. 2011;49(11):3983–5.CrossRefGoogle Scholar
  22. 22.
    Swan DC, Tucker RA, Tortolero-Luna G, et al. Human papillomavirus (HPV) DNA copy number is dependent on grade of cervical disease and HPV type. J Clin Microbiol. 1999;37:1030–4.PubMedPubMedCentralGoogle Scholar
  23. 23.
    Mayrand MH, Coutlee F, Hankins C, et al. Detection of human papillomavirus type 16 DNA in consecutive genital samples does not always represent persistent infection as determined by molecular variant analysis. J Clin Microbiol. 2000;38:3388–9.PubMedPubMedCentralGoogle Scholar
  24. 24.
    Molden T, Kraus I, Skomedal H, Nordstrøm T, Karlsen F. PreTect HPV-Proofer: real-time detection and typing of E6/E7 mRNA from carcinogenic human papillomaviruses. J Virol Methods. 2007;142(1-2):204–12.CrossRefGoogle Scholar
  25. 25.
    Saslow D, Solomon D, Lawson HW, Killackey M, Kulasingam SL, Cain J, 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;62:147–72.CrossRefGoogle Scholar
  26. 26.
    Katki HA, Kinney WK, Fetterman B, et al. Cervical cancer risk for women undergoing concurrent testing for human papillomavirus and cervical cytology: a population-based study in routine clinical practice. Lancet Oncol. 2011;12(7):663–72.CrossRefGoogle Scholar
  27. 27.
    Dijkstra MG, van Zummeren M, Rozendaal L, et al. Safety of extending screening intervals beyond five years in cervical screening programmed with testing for high risk human papillomavirus: 14-year follow-up of population based randomized cohort in the Netherlands. BMJ. 2016;355:i4924.CrossRefGoogle Scholar
  28. 28.
    Saslow D, Runowicz CD, Solomon D, et al. American Cancer Society guideline for the early detection of cervical neoplasia and cancer. CA Cancer J Clin. 2002;52(6):342–62.CrossRefGoogle Scholar
  29. 29.
    Goldie SJ, Kim JJ, Wright TC. Cost-effectiveness of human papillomavirus DNA testing for cervical cancer screening in women aged 30 years or more. Obstet Gynecol. 2004;103(4):619–31.CrossRefGoogle Scholar
  30. 30.
    Mayrand MH, Duarte-Franco E, Rodrigues I, et al. Human papillomavirus DNA versus papanicolaou screening tests for cervical cancer. N Engl J Med. 2007;357(16):1579–88.CrossRefGoogle Scholar
  31. 31.
    Arbyn M, Ronco G, Anttila A, et al. Evidence regarding human papillomavirus testing in secondary prevention of cervical cancer. Vaccine. 2012;30(Suppl 5):F88–99.CrossRefGoogle Scholar
  32. 32.
    Kitchener HC, Gilham C, Sargent A, et al. A comparison of HPV DNA testing and liquid based cytology over three rounds of primary cervical screening: extended follow up in the ARTISTIC trial. Eur J Cancer. 2011;47:864–71.CrossRefGoogle Scholar
  33. 33.
    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;125(2):330–7.Google Scholar
  34. 34.
    Castle PE, Rodriguez AC, Burk RD, et al. Short-term persistence and risk of cervical precancer and cancer: population-based cohort study. BMJ. 2009;339:b2569.CrossRefGoogle Scholar
  35. 35.
    Carozzi F, Gillio-Tos A, Confortini M, et al. Risk of high-grade cervical intraepithelial neoplasia during follow-up in HPV-positive women according to baseline p16-INK4A results: a prospective analysis of a nested sub study of the NTCC randomized controlled trial. Lancet Oncol. 2013;14:168–76.CrossRefGoogle Scholar
  36. 36.
    Arbyn M, Roelens J, Cuschieri K, et al. The APTIMA HPV assay versus the hybrid capture 2 test in triage of women with ASC-US or LSIL cervical cytology: a meta-analysis of the diagnostic accuracy. Int J Cancer. 2013;132:101–8.CrossRefGoogle Scholar
  37. 37.
    Strander B, Andersson-Ellstrom A, Milsom I, et al. Long-term risk of invasive cancer after treatment for cervical intraepithelial neoplasia grade 3: population-based cohort study. BMJ. 2007;335:1077.CrossRefGoogle Scholar
  38. 38.
    Rebolj M, Helmerhorst T, Habbema D, et al. Risk of cervical cancer after completed post-treatment follow-up of cervical intraepithelial neoplasia: population-based cohort study. BMJ. 2012;345:e6855.CrossRefGoogle Scholar
  39. 39.
    Kocken M, Helmerhorst TJM, Berkhof J, Louwers JA, Nobbenhuis MAE, Bais AG, et al. Risk of recurrent high-grade cervical intraepithelial neoplasia after successful treatment: a long-term multi-cohort study. Lancet Oncol. 2011;12(5):441–50.CrossRefGoogle Scholar
  40. 40.
    Arbyn M, Paraskevaidis E, Martin-Hirsche P, et al. Clinical utility of HPV–DNA detection: triage of minor cervical lesions, follow-up of women treated for high-grade CIN: an update of pooled evidence. Gynecol Oncol. 2005;99:S7–11.CrossRefGoogle Scholar
  41. 41.
    Chan BKS, Melnikow J, Slee CA, et al. Posttreatment human papillomavirus testing for recurrent cervical intraepithelial neoplasia: a systematic review. Am J Obstet Gynecol. 2009;200:422.e1–9.CrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Satinder Kaur
    • 1
  • Shilpa Jamwal
    • 1
  1. 1.Department of Gynae-OncologyDharamshila Narayana Superspeciality HospitalNew DelhiIndia

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