Current Obstetrics and Gynecology Reports

, Volume 3, Issue 2, pp 107–115

Detection and Clinical Management of Cervical Pathology in the Era of HPV

Management of HPV and Associated Cervical Lesions (C-H Lai, Section Editor)


While infection with high-risk (HR) human papillomavirus (HPV) is central to cervical carcinogenesis, natural history studies show that both low- and high-grade cervical intraepithelial neoplasia (CIN) lesions are very early manifestations of HR-HPV infection. Most high- and low-grade lesions are self limited, and only those HR-HPV infections capable of persisting for decades are at risk of progression. Our new understanding of the natural history of HPV associated lesions has dramatically changed cervical cancer screening, classification and management of cervical lesions. As an increasing proportion of women are vaccinated against those oncogenic-HPVs responsible for most cervical cancers, the positive predictive value of cytology and HPV testing for identification of women at risk for cancer will decrease. New biomarkers, capable of identifying those high-grade lesions which are truly at risk of progression and need treatment, will need to be developed to serve as adjuncts to morphology and patient management.


Human papillomavirus HPV Cervical cancer Natural history Cervical intraepithelial neoplasia CIN Management Clearance Persistence Transmission Immune response 


Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. 1.
    Burk RD, Ho GY, Beardsley L, Lempa M, Peters M, Bierman R. Sexual behavior and partner characteristics are the predominant risk factors for genital human papillomavirus infection in young women. J Infect Dis. 1996;174(4):679–89.PubMedCrossRefGoogle Scholar
  2. 2.
    Wheeler CM, Parmenter CA, Hunt WC, et al. Determinants of genital human papillomavirus infection among cytologically normal women attending the University of New Mexico student health center. Sex Transm Dis. 1993;20(5):286–9.PubMedCrossRefGoogle Scholar
  3. 3.
    Tarkowski TA, Koumans EH, Sawyer M, et al. Epidemiology of human papillomavirus infection and abnormal cytologic test results in an urban adolescent population. J Infect Dis. 2004;189(1):46–50.PubMedCrossRefGoogle Scholar
  4. 4.
    Ferenczy A, Bergeron C, Richart RM. Human papillomavirus DNA in fomites on objects used for the management of patients with genital human papillomavirus infections. Obstet Gynecol. 1989;74(6):950–4.PubMedGoogle Scholar
  5. 5.
    Ferenczy A, Bergeron C, Richart RM. Human papillomavirus DNA in CO2 laser-generated plume of smoke and its consequences to the surgeon. Obstet Gynecol. 1990;75(1):114–8.PubMedGoogle Scholar
  6. 6.
    Medeiros LR, Ethur ABM, Hilgert JB, et al. Vertical transmission of the human papillomavirus: a systematic quantitative review. Cad Saude Publica. 2005;21(4):1006–15.PubMedCrossRefGoogle Scholar
  7. 7.
    Tseng CJ, Liang CC, Soong YK, Pao CC. Perinatal transmission of human papillomavirus in infants: relationship between infection rate and mode of delivery. Obstet Gynecol. 1998;91(1):92–6.PubMedCrossRefGoogle Scholar
  8. 8.•
    Stanley M. HPV – immune response to infection and vaccination. Infect Agent Cancer. 2010;5:19. Great review of the immune mechanisms in response to HPV infection and HPV vaccination.PubMedCentralPubMedCrossRefGoogle Scholar
  9. 9.
    Herfs M, Yamamoto Y, Laury A, et al. A discrete population of squamocolumnar junction cells implicated in the pathogenesis of cervical cancer. Proc Natl Acad Sci U S A. 2012;109(26):10516–21.PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    Trottier H, Franco EL. The epidemiology of genital human papillomavirus infection. Vaccine. 2006;24 Suppl 1:S4–15.CrossRefGoogle Scholar
  11. 11.
    Fisher M, Rosenfeld WD, Burk RD. Cervicovaginal human papillomavirus infection in suburban adolescents and young adults. J Pediatr. 1991;119(5):821–5.PubMedCrossRefGoogle Scholar
  12. 12.
    Ley C, Bauer HM, Reingold A, et al. Determinants of genital human papillomavirus infection in young women. J Natl Cancer Inst. 1991;83(14):997–1003.PubMedCrossRefGoogle Scholar
  13. 13.
    Melkert PW, Hopman E, van den Brule AJ, et al. Prevalence of HPV in cytomorphologically normal cervical smears, as determined by the polymerase chain reaction, is age-dependent. Int J Cancer. 1993;53(6):919–23.PubMedCrossRefGoogle Scholar
  14. 14.
    Schiffman MH. Recent progress in defining the epidemiology of human papillomavirus infection and cervical neoplasia. J Natl Cancer Inst. 1992;84(6):394–8.PubMedCrossRefGoogle Scholar
  15. 15.
    Baseman JG, Koutsky LA. The epidemiology of human papillomavirus infections. J Clin Virol. 2005;32:S16–24.PubMedCrossRefGoogle Scholar
  16. 16.
    Gravitt PE. The known unknowns of HPV natural history. J Clin Invest. 2011;121(12):4593–9.PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Kulasingam SL, Hughes JP, Kiviat NB, et al. Evaluation of human papillomavirus testing in primary screening for cervical abnormalities: comparison of sensitivity, specificity, and frequency of referral. JAMA. 2002;288(14):1749–57.PubMedCrossRefGoogle Scholar
  18. 18.
    Ho GY, Bierman R, Beardsley L, Chang CJ, Burk RD. Natural history of cervicovaginal papillomavirus infection in young women. N Engl J Med. 1998;338(7):423–8.PubMedCrossRefGoogle Scholar
  19. 19.
    Richardson H, Kelsall G, Tellier P, et al. The natural history of type-specific human papillomavirus infections in female university students. Cancer Epidemiol Biomarkers Prev. 2003;12(6):485–90.PubMedGoogle Scholar
  20. 20.•
    Jaisamrarn U, Castellsague X, Garland SM, et al. Natural history of progression of HPV infection to cervical lesion or clearance: analysis of the control arm of the large, randomized PATRICIA study. PLoS One. 2013;8(11):e79260. Large prospective study with valuable data on HPV infection clearanc, persistence and risk of progression.PubMedCentralPubMedCrossRefGoogle Scholar
  21. 21.
    Woodman CB, Collins S, Winter H, et al. Natural history of cervical human papillomavirus infection in young women: a longitudinal cohort study. Lancet. 2001;357(9271):1831–6.PubMedCrossRefGoogle Scholar
  22. 22.
    Franco EL, Villa LL, Sobrinho JP, et al. Epidemiology of acquisition and clearance of cervical human papillomavirus infection in women from a high-risk area for cervical cancer. J Infect Dis. 1999;180(5):1415–23.PubMedCrossRefGoogle Scholar
  23. 23.
    Liaw KL, Glass AG, Manos MM, et al. Detection of human papillomavirus DNA in cytologically normal women and subsequent cervical squamous intraepithelial lesions. J Natl Cancer Inst. 1999;91(11):954–60.PubMedCrossRefGoogle Scholar
  24. 24.
    Liaw KL, Hildesheim A, Burk RD, et al. A prospective study of human papillomavirus (HPV) type 16 DNA detection by polymerase chain reaction and its association with acquisition and persistence of other HPV types. J Infect Dis. 2001;183(1):8–15.PubMedCrossRefGoogle Scholar
  25. 25.
    Munoz N, Bosch FX, de Sanjose S, et al. Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med. 2003;348(6):518–27.PubMedCrossRefGoogle Scholar
  26. 26.
    Slavinsky III J, Kissinger P, Burger L, Boley A, DiCarlo RP, Hagensee ME. Seroepidemiology of low and high oncogenic risk types of human papillomavirus in a predominantly male cohort of STD clinic patients. Int J STD AIDS. 2001;12(8):516–23.PubMedCrossRefGoogle Scholar
  27. 27.
    Touze A, de Sanjose S, Coursaget P, et al. Prevalence of anti-human papillomavirus type 16, 18, 31, and 58 virus-like particles in women in the general population and in prostitutes. J Clin Microbiol. 2001;39(12):4344–8.PubMedCentralPubMedCrossRefGoogle Scholar
  28. 28.
    Wang SS, Schiffman M, Shields TS, et al. Seroprevalence of human papillomavirus-16, -18, -31, and -45 in a population-based cohort of 10000 women in Costa Rica. Br J Cancer. 2003;89(7):1248–54.PubMedCentralPubMedCrossRefGoogle Scholar
  29. 29.
    Winer RL, Koutsky LA. Chapter 28: genital human papillomavirus infection. In: Holmes KK, Sparling PF, Stamm WE, et al., editors. Sexually transmitted diseases. 4th ed. New York: McGraw-Hill; 2008. p. 489–508.Google Scholar
  30. 30.
    Stone KM, Karem KL, Sternberg MR, et al. Seroprevalence of human papillomavirus type 16 infection in the United States. J Infect Dis. 2002;186(10):1396–402.PubMedCrossRefGoogle Scholar
  31. 31.
    Carter JJ, Koutsky LA, Wipf GC, et al. The natural history of human papillomavirus type 16 capsid antibodies among a cohort of university women. J Infect Dis. 1996;174(5):927–36.PubMedCrossRefGoogle Scholar
  32. 32.
    Ho GY, Studentsov YY, Bierman R, Burk RD. Natural history of human papillomavirus type 16 virus-like particle antibodies in young women. Cancer Epidemiol Biomarkers Prev. 2004;13(1):110–6.PubMedCrossRefGoogle Scholar
  33. 33.
    Carter JJ, Koutsky LA, Hughes JP, et al. Comparison of human papillomavirus types 16, 18, and 6 capsid antibody responses following incident infection. J Infect Dis. 2000;181(6):1911–9.PubMedCrossRefGoogle Scholar
  34. 34.
    de Gruijl TD, Bontkes HJ, Walboomers JM, et al. Immune responses against human papillomavirus (HPV) type 16 virus-like particles in a cohort study of women with cervical intraepithelial neoplasia. I. Differential T-helper and IgG responses in relation to HPV infection and disease outcome. J Gen Virol. 1999;80(Pt 2):399–408.PubMedGoogle Scholar
  35. 35.
    Harper DM, Franco EL, Wheeler C, et al. Efficacy of a bivalent L1 virus-like particle vaccine in prevention of infection with human papillomavirus types 16 and 18 in young women: a randomised controlled trial. Lancet. 2004;364(9447):1757–65.PubMedCrossRefGoogle Scholar
  36. 36.
    Villa LL, Ault KA, Giuliano AR, et al. Immunologic responses following administration of a vaccine targeting human papillomavirus Types 6, 11, 16, and 18. Vaccine. 2006;24(27–28):5571–83.PubMedCrossRefGoogle Scholar
  37. 37.
    De Carvalho N, Teixeira J, Roteli-Martins CM, et al. Sustained efficacy and immunogenicity of the HPV-16/18 AS04-adjuvanted vaccine up to 7.3 years in young adult women. Vaccine. 2010;28(38):6247–55.PubMedCrossRefGoogle Scholar
  38. 38.
    Rowhani-Rahbar A, Mao C, Hughes JP, et al. Longer term efficacy of a prophylactic monovalent human papillomavirus type 16 vaccine. Vaccine. 2009;27(41):5612–9.PubMedCentralPubMedCrossRefGoogle Scholar
  39. 39.
    Steben M, Duarte-Franco E. Human papillomavirus infection: epidemiology and pathophysiology. Gynecol Oncol. 2007;107(2 Supp 1):S2–5.PubMedCrossRefGoogle Scholar
  40. 40.
    Safaeian M, Porras C, Schiffman M, et al. Epidemiological study of anti-HPV16/18 seropositivity and subsequent risk of HPV16 and -18 infections. J Natl Cancer Inst. 2010;102(21):1653–62.PubMedCentralPubMedCrossRefGoogle Scholar
  41. 41.
    Stanley MA. Epithelial cell responses to infection with human papillomavirus. Clin Microbiol Rev. 2012;25(2):215.PubMedCentralPubMedCrossRefGoogle Scholar
  42. 42.
    Hildesheim A, Schiffman MH, Gravitt PE, et al. Persistence of type-specific human papillomavirus infection among cytologically normal women. J Infect Dis. 1994;169(2):235–40.PubMedCrossRefGoogle Scholar
  43. 43.
    Rodriguez AC, Schiffman M, Herrero R, et al. Longitudinal study of human papillomavirus persistence and cervical intraepithelial neoplasia grade 2/3: critical role of duration of infection. J Natl Cancer Inst. 2010;102(5):315–24.PubMedCentralPubMedCrossRefGoogle Scholar
  44. 44.
    Nobbenhuis MA, Walboomers JM, Helmerjorst TJ, et al. Relation of human papillomavirus status to cervical lesions and consequences for cervical-cancer screening: a prosepective study. Lancet. 1999;354(9172):20–5.PubMedCrossRefGoogle Scholar
  45. 45.
    Kjaer SK, Frederiksen K, Munk C, Iftner T. Long-term absolute risk of cervical intraepithelial neoplasia grade 3 or worse following human papillomavirus infection: role of persistence. J Natl Cancer Inst. 2010;102(19):1478–88.PubMedCentralPubMedCrossRefGoogle Scholar
  46. 46.
    Koutsky LA, Holmes KK, Critchlow CW, et al. A cohort study of the risk of cervical intraepithelial neoplasia grade 2 or 3 in relation to papillomavirus infection. N Engl J Med. 1992;327(18):1272–8.PubMedCrossRefGoogle Scholar
  47. 47.
    Trottier H, Mahnud SM, Lindsay L, et al. Persistence of an incident human papillomavirus infection and timing of cervical lesions in previously unexposed young women. Cancer Epidemiol Biomarkers Prev. 2009;18(3):854–62.PubMedCrossRefGoogle Scholar
  48. 48.
    Ho GY, Burk RD, Klein S, et al. Persistent human papillomavirus infection as a risk factor for persistent cervical dysplasia. J Natl Cancer Inst. 1995;87(18):1365–71.PubMedCrossRefGoogle Scholar
  49. 49.
    Schlecht NF, Kulaga S, Robitaille J, et al. Persistent human papillomavirus infection as a predictor for cervical intraepithelial neoplasia. JAMA. 2001;286(24):3106–14.PubMedCrossRefGoogle Scholar
  50. 50.
    Schiffman M, Herrero R, Desalle R. The carcinogenicity of human papillomavirus types reflects viral evolution. Virology. 2005;337(1):76–84.PubMedCrossRefGoogle Scholar
  51. 51.
    Winer RL, Lee SK, Hughes JP, Adam DE, Kiviat NB, Koutsky LA. Genital human papillomavirus infection: incidence and risk factors in a cohort of female university students. Am J Epidemiol. 2003;157(3):218–26.PubMedCrossRefGoogle Scholar
  52. 52.
    Mao C, Koutsky LA, Ault KA, et al. Efficacy of human papillomavirus-16 vaccine to prevent cervical intraepithelial neoplasia: a randomized controlled trial. Obstet Gynecol. 2006;107(1):18–27.PubMedCrossRefGoogle Scholar
  53. 53.
    Woodman CB, Collins S. A critique of cohort studies examining the role of human papillomavirus infection in cervical neoplasia. BJOG. 2002;109(12):1311–8.PubMedCrossRefGoogle Scholar
  54. 54.
    Kiviat NB, Critchlow CW, Kurman RJ. Reassessment of the morphological continuum of cervical intraepithelial lesions: does it reflect different stages in the progression to cervical carcinoma? IARC Sci Publ. 1992;119:59–66.PubMedGoogle Scholar
  55. 55.•
    Moscicki AB, Ma Y, Wibbelsman C, et al. Rate of and risks for regression of cervical intraepithelial neoplasia 2 in adolescents and young women. Obstet Gynecol. 2010;116(6):1373–80. Prospective study investigating the natural history of CIN2 in adolescents and young women.PubMedCentralPubMedCrossRefGoogle Scholar
  56. 56.
    McAllum B, Sykes PH, Sadler L, Macnab H, Simcock BJ, Mekhail AK. Is the treatment of CIN 2 always necessary in women under 25 years old? Am J Obstet Gynecol. 2011;205(5):478.e1–7.Google Scholar
  57. 57.
    Insinga RP, Dasbach EJ, Elbasha EH. Epidemiologic natural history and clinical management of human papillomavirus (HPV) disease: a critical and systematic review of the literature in the development of an HPV dynamic transmission model. BMC Infect Dis. 2009;9:119.PubMedCentralPubMedCrossRefGoogle Scholar
  58. 58.
    Castle PE, Schiffman M, Wheeler CM, Solomon D. Evidence for frequent regression of cervical intraepithelial neoplasia-grade 2. Obstet Gynecol. 2009;113(1):18–25.PubMedCentralPubMedCrossRefGoogle Scholar
  59. 59.
    National Cancer Institute, Bethesda, MD. Surveillance, epidemiology, and end results program. At: Accessed 20 Jan 2014.
  60. 60.
    Fahey MT, Irwig L, Macaskill P. Meta-analysis of Pap test accuracy. Am J Epidemiol. 1995;141(7):680–9.PubMedGoogle Scholar
  61. 61.
    Cuzick J, Szarewski A, Terry G, et al. Human papillomavirus testing in primary cervical screening. Lancet. 1995;345(8964):1533–6.PubMedCrossRefGoogle Scholar
  62. 62.
    Sedlacek TV. Cost-effectiveness of methods to enhance sensitivity of Papanicolaou testing. Jama. 1999;282(15):1419–20.PubMedCrossRefGoogle Scholar
  63. 63.
    Joste NE, Rushing L, Granados R, et al. Bethesda classification of cervicovaginal smears: reproducibility and viral correlates. Hum Pathol. 1996;27(6):581–5.PubMedCrossRefGoogle Scholar
  64. 64.
    Ismail SM, Colclough AB, Dinnen JS, et al. Observer variation in histopathological diagnosis and grading of cervical intraepithelial neoplasia. BMJ. 1989;298(6675):707–10.PubMedCentralPubMedCrossRefGoogle Scholar
  65. 65.
    Dalla Palma P, Giorgi Rossi P, Collina G, et al. The reproducibility of CIN diagnoses among different pathologists: data from histology reviews from a multicenter randomized study. Am J Clin Pathol. 2009;132(1):125–32.PubMedCrossRefGoogle Scholar
  66. 66.
    Miller AB. An epidemiological perspective on cancer screening. Clin Biochem. 1995;28(1):41–8.PubMedCrossRefGoogle Scholar
  67. 67.
    NIH releases consensus statement on cervical cancer. Am Fam Physician. 1996;54(7):2310, 2315-6.Google Scholar
  68. 68.
    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. Am J Clin Pathol. 2012;137(4):516–42.PubMedCrossRefGoogle Scholar
  69. 69.•
    Massad LS, Einstein MH, Huh WK, et al. 2012 updated consensus guidelines for the management of abnormal cervical cancer screening tests and cancer precursors. Obstet Gynecol. 2013;121(4):829–46. Latest ASCCP Guidelines for the management of abnormal cervical cancer screening tests and precursor lesions.PubMedCrossRefGoogle Scholar
  70. 70.
    Kulasingam SL, Kim JJ, Lawrence WF, et al. Cost-effectiveness analysis based on the atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion triage study (ALTS). J Natl Cancer Inst. 2006;98(2):92–100.PubMedCrossRefGoogle Scholar
  71. 71.
    Arbyn M, Sasieni P, Meijer CJ, Clavel C, Koliopoulos G, Dillner J. Chapter 9: clinical applications of HPV testing: a summary of meta-analyses. Vaccine. 2006;24 Suppl 3:78–89.CrossRefGoogle Scholar
  72. 72.
    Carozzi F, Confortini M, Cecchini S, et al. Triage with human papillomavirus testing of women with cytologic abnormalities prompting referral for colposcopy assessment. Cancer. 2005;105(1):2–7.PubMedGoogle Scholar
  73. 73.
    Arbyn M, Roelens J, Simoens C, et al. Human papillomavirus testing versus repeat cytology for triage of minor cytological cervical lesions. Cochrane Database Syst Rev. 2013;3, CD008054.PubMedGoogle Scholar
  74. 74.
    Arbyn M, Roelens J, Cuschieri K, et al. The APTIMA HPV assay versus the Hybrid Capture II test in triage of women with ASC-US or LSIL cervical cytology: a meta-analysis of the diagnostic accuracy. Int J Cancer. 2013;132(1):101–8.PubMedCrossRefGoogle Scholar
  75. 75.
    Kyrgiou M, Koliopoulos G, Martin-Hirsch P, Arbyn M, Prendiville W, Paraskevaidis E. Obstetric outcomes after conservative treatment for intraepithelial or early invasive cervical lesions: systematic review and meta-analysis. Lancet. 2006;367(9509):489–98.PubMedCrossRefGoogle Scholar
  76. 76.
    Bulkmans NW, Berkhof J, Rozendaal L, et al. Human papillomavirus DNA testing for the detection of cervical intraepithelial neoplasia grade 3 and cancer: 5-year follow-up of a randomised controlled implementation trial. Lancet. 2007;370(9601):1764–72.PubMedCrossRefGoogle Scholar
  77. 77.
    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.PubMedCrossRefGoogle Scholar
  78. 78.
    Naucler P, Ryd W, Tornberg S, et al. Human papillomavirus and Papanicolaou tests to screen for cervical cancer. N Engl J Med. 2007;357(16):1589–97.PubMedCrossRefGoogle Scholar
  79. 79.
    Ronco G, Giorgi-Rossi P, Carozzi F, et al. Results at recruitment from a randomized controlled trial comparing human papillomavirus testing alone with conventional cytology as the primary cervical cancer screening test. J Natl Cancer Inst. 2008;100(7):492–501.PubMedCrossRefGoogle Scholar
  80. 80.
    Ronco G, Giorgi-Rossi P, Carozzi F, et al. Human papillomavirus testing and liquid-based cytology in primary screening of women younger than 35 years: results at recruitment for a randomised controlled trial. Lancet Oncol. 2006;7(7):547–55.PubMedCrossRefGoogle Scholar
  81. 81.
    Koliopoulos G, Arbyn M, Martin-Hirsch P, Kyrgiou M, Prendiville W, Paraskevaidis E. Diagnostic accuracy of human papillomavirus testing in primary cervical screening: a systematic review and meta-analysis of non-randomized studies. Gynecol Oncol. 2007;104(1):232–46.PubMedCrossRefGoogle Scholar
  82. 82.
    Cuzick J, Arbyn M, Sankaranarayanan R, et al. Overview of human papillomavirus-based and other novel options for cervical cancer screening in developed and developing countries. Vaccine. 2008;26 Suppl 10:29–41.CrossRefGoogle Scholar
  83. 83.
    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.PubMedCrossRefGoogle Scholar
  84. 84.
    Meijer CJ, Berkhof H, Heideman DA, Hesselink AT, Snijders PJ. Validation of high-risk HPV tests for primary cervical screening. J Clin Virol. 2009;46 Suppl 3:S1–4.PubMedCrossRefGoogle Scholar
  85. 85.
    Ronco G, Dillner J, Elfstrom KM et al. Efficacy of HPV-based screening for prevention of invasive cervical cancer: follow-up of four European randomised controlled trials. Lancet 2013 Nov 1.Google Scholar
  86. 86.
    Carozzi F, Visioli CB, Confortini M, et al. hr-HPV testing in the follow-up of women with cytological abnormalities and negative colposcopy. Br J Cancer. 2013;109(7):1766–74.PubMedCrossRefGoogle Scholar
  87. 87.
    Dillner J, Rebolj M, Birembaut P, et al. Long term predictive values of cytology and human papillomavirus testing in cervical cancer screening: joint European cohort study. BMJ. 2008;337:a1754.PubMedCentralPubMedCrossRefGoogle Scholar
  88. 88.
    Lynge E, Rebolj M. Primary HPV screening for cervical cancer prevention: results from European trials. Nat Rev Clin Oncol. 2009;6(12):699–706.PubMedCrossRefGoogle Scholar
  89. 89.
    Kotaniemi-Talonen L, Nieminen P, Anttila A, Hakama M. Routine cervical screening with primary HPV testing and cytology triage protocol in a randomised setting. Br J Cancer. 2005;93(8):862–7.PubMedCentralPubMedCrossRefGoogle Scholar
  90. 90.
    Leinonen M, Nieminen P, Kotaniemi-Talonen L, et al. Age-specific performance of cervical cancer screening with primary HPV DNA test compared to conventional cytological screening in a randomised setting. J Natl Cancer Inst. 2009;101(23):1612–23.PubMedCrossRefGoogle Scholar
  91. 91.
    Anttila A, Kotaniemi-Talonen L, Leinonen M, et al. Rate of cervical cancer, severe intraepithelial neoplasia, and adenocarcinoma in situ in primary HPV DNA screening with cytology triage: randomised study within organised screening programme. BMJ. 2010;340:c1804.PubMedCentralPubMedCrossRefGoogle Scholar
  92. 92.
    Richart RM. Natural history of cervical intraepithelial neoplasia. Clin Obstet Gynecol. 1968;5:748–84.Google Scholar
  93. 93.
    American Society for Colposcopy and Cervical Pathology, Frederick, MD. Updated consensus guidelines for managing abnormal cervical cancer screening tests and cancer precursors, april 2013. At: Accessed 20 Jan 2014.
  94. 94.
    Ostor AG. Natural history of cervical intraepithelial neoplasia: a critical review. Int J Gynecol Pathol. 1993;12(2):186–92.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Department of Pathology and Laboratory MedicineAllegheny General HospitalPittsburghUSA
  2. 2.Department of Pathology, Harborview Medical CenterUniversity of WashingtonSeattleUSA

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