The Potential Utility of HPV Genotyping in Screening and Clinical Management

Detection of specific human papillomavirus (HPV) genotypes, or HPV genotyping, may be useful for differentiating between those women who are carcinogenic HPV-positive at lower and higher risk for cervical precancer and cancer. Considerable evidence already exists that the absolute risk for cervical precancer and cancer varies considerably among specific HPV genotypes, and that detection of HPV-16 and -18 may have clinical usefulness, especially among women who tested positive for carcinogenic HPV and have negative cytology. Detection of persistent carcinogenic HPV is strongly associated with cervical precancer and cancer and strongly predicts its development, and might be used to monitor the outcomes of HPV infections. However, several practical considerations must be addressed before HPV genotyping can be used in screening and clinical management.

If the inline PDF is not rendering correctly, you can download the PDF file here.

Correspondence: Philip E. Castle, PhD, MPH, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Boulevard, Room 5004, EPS MSC 7234, Bethesda, MD 20892-7234. E-mail: castlep@mail.nih.gov

References

  • 1.

    IARC Handbooks of Cancer PreventionVol.10: Cervix Cancer Screening. Lyon, France: IARC Press; 2005.

  • 2.

    JemalASiegelRWardE. Cancer statistics, 2007. CA Cancer J Clin2007;57:4366.

  • 3.

    KitchenerHCCastlePECoxJT. Chapter 7: achievements and limitations of cervical cytology screening. Vaccine2006;24(Suppl 3):S6370.

  • 4.

    NandaKMcCroryDCMyersER. Accuracy of the Papanicolaou test in screening for and follow-up of cervical cytologic abnormalities: a systematic review. Ann Intern Med2000;132:810819.

    • Search Google Scholar
    • Export Citation
  • 5.

    CuzickJClavelCPetryKU. Overview of the European and North American studies on HPV testing in primary cervical cancer screening. Int J Cancer2006;119:10951101.

    • Search Google Scholar
    • Export Citation
  • 6.

    StolerMHSchiffmanM. Interobserver reproducibility of cervical cytologic and histologic interpretations: realistic estimates from the ASCUS-LSIL Triage Study. JAMA2001;285:15001505.

    • Search Google Scholar
    • Export Citation
  • 7.

    KurmanRJHensonDEHerbstAL. Interim guidelines for management of abnormal cervical cytology. The 1992 National Cancer Institute Workshop. JAMA1994;271:18661869.

    • Search Google Scholar
    • Export Citation
  • 8.

    WalboomersJMJacobsMVManosMM. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol1999;189:1219.

    • Search Google Scholar
    • Export Citation
  • 9.

    MunozNBoschFXde SanjoseS. Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med2003;348:518527.

    • Search Google Scholar
    • Export Citation
  • 10.

    SchiffmanMHBauerHMHooverRN. Epidemiologic evidence showing that human papillomavirus infection causes most cervical intraepithelial neoplasia. J Natl Cancer Inst1993;85:958964.

    • Search Google Scholar
    • Export Citation
  • 11.

    WrightTCJrSchiffmanM. Adding a test for human papillomavirus DNA to cervical-cancer screening. N Engl J Med2003;348:489490.

  • 12.

    SolomonDSchiffmanMTaroneR. Comparison of three management strategies for patients with atypical squamous cells of undetermined significance: baseline results from a randomized trial. J Natl Cancer Inst2001;93:293299.

    • Search Google Scholar
    • Export Citation
  • 13.

    ArbynMBuntinxFVan RanstM. Virologic versus cytologic triage of women with equivocal Pap smears: a meta-analysis of the accuracy to detect high-grade intraepithelial neoplasia. J Natl Cancer Inst2004;96:280293.

    • Search Google Scholar
    • Export Citation
  • 14.

    ArbynMSasieniPMeijerCJ. Chapter 9: clinical applications of HPV testing: a summary of meta-analyses. Vaccine2006;24(Suppl 3):S7889.

  • 15.

    ManosMMKinneyWKHurleyLB. Identifying women with cervical neoplasia: using human papillomavirus DNA testing for equivocal Papanicolaou results. JAMA1999;281:16051610.

    • Search Google Scholar
    • Export Citation
  • 16.

    KulasingamSLKimJJLawrenceWF. Cost-effectiveness analysis based on the atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion Triage Study (ALTS). J Natl Cancer Inst2006;98:92100.

    • Search Google Scholar
    • Export Citation
  • 17.

    KimJJWrightTCGoldieSJ. Cost-effectiveness of human papillomavirus DNA testing in the United Kingdom, The Netherlands, France, and Italy. J Natl Cancer Inst2005;97:888895.

    • Search Google Scholar
    • Export Citation
  • 18.

    CuzickJSzarewskiACubieH. Management of women who test positive for high-risk types of human papillomavirus: the HART study. Lancet2003;362:18711876.

    • Search Google Scholar
    • Export Citation
  • 19.

    RoncoGGiorgi-RossiPCarozziF. 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 Oncol2006;7:547555.

    • Search Google Scholar
    • Export Citation
  • 20.

    ShermanMELorinczATScottDR. Baseline cytology, human papillomavirus testing, and risk for cervical neoplasia: a 10-year cohort analysis. J Natl Cancer Inst2003;95:4652.

    • Search Google Scholar
    • Export Citation
  • 21.

    RoncoGSegnanNGiorgi-RossiP. Human papillomavirus testing and liquid-based cytology: results at recruitment from the new technologies for cervical cancer randomized controlled trial. J Natl Cancer Inst2006;98:765774.

    • Search Google Scholar
    • Export Citation
  • 22.

    KjaerSHogdallEFrederiksenK. The absolute risk of cervical abnormalities in high-risk human papillomavirus-positive, cytologically normal women over a 10-year period. Cancer Res2006;66:1063010636.

    • Search Google Scholar
    • Export Citation
  • 23.

    WalkerJLWangSSSchiffmanMSolomonD. Predicting absolute risk of CIN3 during post-colposcopic follow-up: results from the ASCUS-LSIL Triage Study (ALTS). Am J Obstet Gynecol2006;195:341348.

    • Search Google Scholar
    • Export Citation
  • 24.

    KreimerARGuidoRSSolomonD. Human papillomavirus testing following loop electrosurgical excision procedure identifies women at risk for posttreatment cervical intraepithelial neoplasia grade 2 or 3 disease. Cancer Epidemiol Biomarkers Prev2006;15:908914.

    • Search Google Scholar
    • Export Citation
  • 25.

    ArbynMParaskevaidisEMartin-HirschP. 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 Oncol2005;99(3 Suppl):S711.

    • Search Google Scholar
    • Export Citation
  • 26.

    GokMCoupeVMBerkhofJ. HPV16 and increased risk of recurrence after treatment for CIN. Gynecol Oncol2007;104:273275.

  • 27.

    CastlePEWheelerCMSolomonD. Interlaboratory reliability of Hybrid Capture 2. Am J Clin Pathol2004;122:238245.

  • 28.

    CarozziFMDel MistroAConfortiniM. Reproducibility of HPV DNA testing by Hybrid Capture 2 in a screening setting. Am J Clin Pathol2005;124:716721.

    • Search Google Scholar
    • Export Citation
  • 29.

    WrightTCJrSchiffmanMSolomonD. Interim guidance for the use of human papillomavirus DNA testing as an adjunct to cervical cytology for screening. Obstet Gynecol2004;103:304309.

    • Search Google Scholar
    • Export Citation
  • 30.

    SmithJSLindsayLHootsB. Human papillomavirus type distribution in invasive cervical cancer and high-grade cervical lesions: a meta-analysis update. Int J Cancer2007.

    • Search Google Scholar
    • Export Citation
  • 31.

    KhanMJCastlePELorinczAT. The elevated 10-year risk of cervical precancer and cancer in women with human papillomavirus (HPV) type 16 or 18 and the possible utility of type-specific HPV testing in clinical practice. J Natl Cancer Inst2005;97:10721079.

    • Search Google Scholar
    • Export Citation
  • 32.

    ShermanMEWangSSCarreonJDevesaSS. Mortality trends for cervical squamous and adenocarcinoma in the United States. Relation to incidence and survival. Cancer2005;103:12581264.

    • Search Google Scholar
    • Export Citation
  • 33.

    BrayFCarstensenBMollerH. Incidence trends of adenocarcinoma of the cervix in 13 European countries. Cancer Epidemiol Biomarkers Prev2005;14:21912199.

    • Search Google Scholar
    • Export Citation
  • 34.

    BerkhofJBulkmansNWBleekerMC. Human papillomavirus type-specific 18-month risk of high-grade cervical intraepithelial neoplasia in women with a normal or borderline/mildly dyskaryotic smear. Cancer Epidemiol Biomarkers Prev2006;15:12681273.

    • Search Google Scholar
    • Export Citation
  • 35.

    BulkSBerkhofJBulkmansNW. Preferential risk of HPV16 for squamous cell carcinoma and of HPV18 for adenocarcinoma of the cervix compared to women with normal cytology in The Netherlands. Br J Cancer2006;94:171175.

    • Search Google Scholar
    • Export Citation
  • 36.

    BulkmansNWBleekerMCBerkhofJ. Prevalence of types 16 and 33 is increased in high-risk human papillomavirus positive women with cervical intraepithelial neoplasia grade 2 or worse. Int J Cancer2005;117:177181.

    • Search Google Scholar
    • Export Citation
  • 37.

    NauclerPRydWTornbergS. HPV type-specific risks of high-grade CIN during 4 years of follow-up: a population-based prospective study. Br J Cancer2007;97:129132.

    • Search Google Scholar
    • Export Citation
  • 38.

    MitchellHMedleyGGordonIGilesG. Cervical cytology reported as negative and risk of adenocarcinoma of the cervix: no strong evidence of benefit. Br J Cancer1995;71:894897.

    • Search Google Scholar
    • Export Citation
  • 39.

    LorinczATReidRJensonAB. Human papillomavirus infection of the cervix: relative risk associations of 15 common anogenital types. Obstet Gynecol1992;79:328337.

    • Search Google Scholar
    • Export Citation
  • 40.

    BulkSBerkhofJRozendaalL. The contribution of HPV18 to cervical cancer is underestimated using high-grade CIN as a measure of screening efficiency. Br J Cancer2007;96:12341236.

    • Search Google Scholar
    • Export Citation
  • 41.

    KovacicMBCastlePEHerreroR. Relationships of human papillomavirus type, qualitative viral load, and age with cytologic abnormality. Cancer Res2006;66:1011210119.

    • Search Google Scholar
    • Export Citation
  • 42.

    SchiffmanMHerreroRDesalleR. The carcinogenicity of human papillomavirus types reflects viral evolution. Virology2005;20;337:7684.

  • 43.

    SchlechtNFKulagaSRobitailleJ. Persistent human papillomavirus infection as a predictor of cervical intraepithelial neoplasia. JAMA2001;286:31063114.

    • Search Google Scholar
    • Export Citation
  • 44.

    KjaerSKvan den BruleAJPaullG. Type specific persistence of high risk human papillomavirus (HPV) as indicator of high grade cervical squamous intraepithelial lesions in young women: population based prospective follow up study. BMJ2002;325:572.

    • Search Google Scholar
    • Export Citation
  • 45.

    SchiffmanMHerreroRDesalleR. The carcinogenicity of human papillomavirus types reflects viral evolution. Virology2005;337:7684.

  • 46.

    CastlePESchiffmanMHerreroR. A prospective study of age trends in cervical human papillomavirus acquisition and persistence in Guanacaste, Costa Rica. J Infect Dis2005;191:18081816.

    • Search Google Scholar
    • Export Citation
  • 47.

    ShewMLFortenberryJDTuW. Association of condom use, sexual behaviors, and sexually transmitted infections with the duration of genital human papillomavirus infection among adolescent women. Arch Pediatr Adolesc Med2006;160:151156.

    • Search Google Scholar
    • Export Citation
  • 48.

    WheelerCMHuntWCSchiffmanMCastlePE. Human papillomavirus genotypes and the cumulative 2-year risk of cervical precancer. J Infect Dis2006;194:12911299.

    • Search Google Scholar
    • Export Citation
  • 49.

    TrottierHFrancoEL. The epidemiology of genital human papillomavirus infection. Vaccine2006;24(Suppl 1):S115.

  • 50.

    CastlePESchiffmanMHerreroR. A prospective study of age trends in cervical human papillomavirus acquisition and persistence in Guanacaste, Costa Rica. J Infect Dis2005;191:18081816.

    • Search Google Scholar
    • Export Citation
  • 51.

    PlummerMSchiffmanMCastlePE. A 2-year prospective study of human papillomavirus persistence among women with atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion. J Infect Dis2007;195:15821589.

    • Search Google Scholar
    • Export Citation
  • 52.

    RichardsonHKelsallGTellierP. The natural history of type-specific human papillomavirus infections in female university students. Cancer Epidemiol Biomarkers Prev2003;12:485490.

    • Search Google Scholar
    • Export Citation
  • 53.

    KulasingamSLHughesJPKiviatNB. Evaluation of human papillomavirus testing in primary screening for cervical abnormalities: comparison of sensitivity, specificity, and frequency of referral. JAMA2002;288:17491757.

    • Search Google Scholar
    • Export Citation
  • 54.

    HoGYBiermanRBeardsleyL. Natural history of cervicovaginal papillomavirus infection in young women. N Engl J Med1998;338:423428.

  • 55.

    WallinKLWiklundFAngstromT. Type-specific persistence of human papillomavirus DNA before the development of invasive cervical cancer. N Engl J Med1999;341:16331638.

    • Search Google Scholar
    • Export Citation
  • 56.

    CastlePESideriMJeronimoJ. Risk assessment to guide the prevention of cervical cancer. Am J Obstet Gynecol2007;197:356.e16.

  • 57.

    GuidoRSchiffmanMSolomonDBurkeL. Postcolposcopy management strategies for women referred with low-grade squamous intraepithelial lesions or human papillomavirus DNA-positive atypical squamous cells of undetermined significance: a two-year prospective study. Am J Obstet Gynecol2003;188:14011405.

    • Search Google Scholar
    • Export Citation
  • 58.

    GageJCHansonVWAbbeyK. Number of cervical biopsies and sensitivity of colposcopy. Obstet Gynecol2006;108:264272.

  • 59.

    JeronimoJSchiffmanM. Colposcopy at a crossroads. Am J Obstet Gynecol2006;195:349353.

  • 60.

    SchiffmanMAdrianzaME. ASCUS-LSIL Triage Study. Design, methods and characteristics of trial participants. Acta Cytol2000;44:726742.

  • 61.

    CastlePESolomonDSchiffmanMWheelerCM. Human papillomavirus type 16 infections and 2-year absolute risk of cervical precancer in women with equivocal or mild cytologic abnormalities. J Natl Cancer Inst2005;20;97:1066–1071.

    • Search Google Scholar
    • Export Citation
  • 62.

    FUTURE II Study Group.Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions. N Engl J Med2007;356:19151927.

    • Search Google Scholar
    • Export Citation
  • 63.

    GarlandSMHernandez-AvilaMWheelerCM. Quadrivalent vaccine against human papillomavirus to prevent anogenital diseases. N Engl J Med2007;356:19281943.

    • Search Google Scholar
    • Export Citation
  • 64.

    PaavonenJJenkinsDBoschFX. Efficacy of a prophylactic adjuvanted bivalent L1 virus-like-particle vaccine against infection with human papillomavirus types 16 and 18 in young women: an interim analysis of a phase III double-blind, randomised controlled trial. Lancet2007;369:21612170.

    • Search Google Scholar
    • Export Citation
  • 65.

    ASCUS-LSIL Triage Study (ALTS) Group.A randomized trial on the management of low-grade squamous intraepithelial lesion cytology interpretations. Am J Obstet Gynecol2003;188:13931400.

    • Search Google Scholar
    • Export Citation
  • 66.

    ASCUS-LSIL Triage Study (ALTS) Group.Results of a randomized trial on the management of cytology interpretations of atypical squamous cells of undetermined significance. Am J Obstet Gynecol2003;188:13831392.

    • Search Google Scholar
    • Export Citation
  • 67.

    KyrgiouMKoliopoulosGMartin-HirschP. Obstetric outcomes after conservative treatment for intraepithelial or early invasive cervical lesions: systematic review and meta-analysis. Lancet2006;367:489498.

    • Search Google Scholar
    • Export Citation
  • 68.

    KreimerARKatkiHSchiffmanM. Viral determinants of HPV persistence following LEEP treatment for cervical intraepithelial neoplasia grade 2 or 3. Cancer Epidemiol Biomarkers Prev2007;16:1116.

    • Search Google Scholar
    • Export Citation
  • 69.

    XiLFKiviatNBWheelerCM. Risk of cervical intraepithelial neoplasia grade 2 or 3 after loop electrosurgical excision procedure associated with human papillomavirus type 16 variants. J Infect Dis2007;195:13401344.

    • Search Google Scholar
    • Export Citation
  • 70.

    BaeJHKimCJParkTC. Persistence of human papillomavirus as a predictor for treatment failure after loop electrosurgical excision procedure. Int J Gynecol Cancer2007;17:12711277.

    • Search Google Scholar
    • Export Citation
  • 71.

    JainNIrwinKCarlinL. Use of DNA tests for human Papillomavirus infection by US clinicians, 2004. J Infect Dis2007;196:7681.

  • 72.

    MoriartyAT. A rock and a hard place: HPV testing and financial gain. Diagn Cytopathol2007;35:463464.

  • 73.

    SirovichBEWelchHG. Cervical cancer screening among women without a cervix. JAMA2004;291:29902993.

  • 74.

    SolomonDBreenNMcNeelT. Cervical cancer screening rates in the United States and the potential impact of implementation of screening guidelines. CA Cancer J Clin2007;57:105111.

    • Search Google Scholar
    • Export Citation
  • 75.

    CastleP. Cervical cancer screening among women without a cervix. JAMA2004;292:15501551.

  • 76.

    CastlePESchiffmanMGlassAG. Human papillomavirus prevalence in women who have and have not undergone hysterectomies. J Infect Dis2006;194:17021705.

    • Search Google Scholar
    • Export Citation
  • 77.

    CastlePESchiffmanMBrattiMC. A population-based study of vaginal human papillomavirus infection in hysterectomized women. J Infect Dis2004;190:458467.

    • Search Google Scholar
    • Export Citation
  • 78.

    CastlePEStolerMHSolomonDSchiffmanM. The relationship of community biopsy-diagnosed cervical intraepithelial neoplasia grade 2 to the quality control pathology-reviewed diagnoses: an ALTS report. Am J Clin Pathol2007;127:805815.

    • Search Google Scholar
    • Export Citation
  • 79.

    StolerMHCastlePESolomonDSchiffmanM. The expanded use of HPV testing in gynecologic practice per ASCCP-guided management requires the use of well-validated assays. Am J Clin Pathol2007;127:13.

    • Search Google Scholar
    • Export Citation
  • 80.

    BrattiMCRodriguezACSchiffmanM. Description of a seven-year prospective study of human papillomavirus infection and cervical neoplasia among 10000 women in Guanacaste, Costa Rica. Rev Panam Salud Publica2004;15:7589.

    • Search Google Scholar
    • Export Citation

Article Information

PubMed

Google Scholar

Related Articles

Metrics

All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 16 16 5
PDF Downloads 3 3 1
EPUB Downloads 0 0 0