Human Papillomavirus DNA Testing: What, How, and When

Chapter

Abstract

More than 20 years ago, a relationship between Human Papillomavirus (HPV) infection and cervical cancer was recognized. Since then, important strides in understanding the virus have been made, particularly in the following areas: modes of transmission and risk factors associated with transmission, the oncogenic potential of specific viral types and the mechanism by which they cause cancer, and the spectrum of infection, ranging from asymptomatic carrier states to overt warts, preneoplastic lesions, and invasive cancer. Sophisticated new tests for the detection of HPV for screening for cervical cancer precursors and invasive cancer and for the triage of abnormal cervical cytology also have been developed as reported by American College of Obstetricians and Gynecologists (Obstet Gynecol 105:905–918, 2005). Recent evidence has shown that the risk of malignant and premalignant cervical disease and HPV infections varies significantly with age. Furthermore, evidence now shows that treatment for cervical disease carries significant risk for future pregnancies. These factors have led to a reevaluation of the guidelines for the management of premalignant cervical disease as reported by American College of Obstetricians and Gynecologists (Obstet Gynecol 112:1419–1444, 2008). Understanding the immunology of HPV has allowed the development of new and more effective treatment modalities for HPV infection and the development of primary prevention modalities, including HPV vaccines as reported by American College of Obstetricians and Gynecologists (Obstet Gynecol 105:905–918, 2005). Invasive cervical cancer is the second most common female cancer worldwide, with about 493,000 new cases per year. About 273,000 women die from cervical cancer each year, 85% of which take place in developing countries. Cervical cancer has a slow progress from pre-invasive cervical intraepithelial neoplasia (CIN) to invasive phases, meaning that the disease can be diagnosed while in the phase of pre-invasive lesion, and treated successfully thanks to the regular screening of asymptomatic women. Additional diagnostic procedures for preinvasive lesions of the uterine cervix like deoxyribonuclaic acid (DNA) cytometry (flow cytometry) can point to dysplasia that can progress to severe stages, such as high-grade (HG) squamous intraepithelial lesions (H-SIL). If the level of chromosomal disturbance is higher (aneuploidy), it is more probable that H-SIL will develop. Laser screening of cells extracted with modern cytologic screening liquid-based cytology enables us to automatically measure ploidy (chromosome regularity, or irregularity) and polymerase chain reaction (PCR) provides analysis of HPV types. These methods are recommended for a routine check-up of borderline cervical lesions in order to anticipate ones likely to regress or progress as reported by Grubisić et al. (Coll Antropol 33:1431–1436, 2009). HPV also causes a proportion of other cancers, including vulvar, vaginal, anal, penile, and oropharyngeal cancers. Although cervical cancer screening, primarily with the Papanicolaou (Pap) smear, has reduced the incidence of this cancer in industrialized countries, cervical cancer remains the second most common cause of death from cancer in women worldwide, because the developing world has lacked the resources for widespread, high-quality screening. In addition to advances in Pap smear technology, the identification of HPV as the etiologic agent has produced two recent advances that may have a major impact on approaches to reduce the incidence of this disease. The first is the development of a preventive vaccine, the current versions of which appear to prevent close to 100% of persistent genital infection and disease caused by HPV-16 and HPV-18. Future second-generation vaccines may be able to protect against oncogenic infections by a broader array of HPV types. The second is the incorporation of HPV testing into screening programs. In women aged >30 years, HPV testing can identify HG CIN earlier than Pap smears with acceptable rates of specificity. These results, together with the high sensitivity of HPV testing, suggest that such testing could permit increased intervals for screening. An inexpensive HPV test in development, if successful, may be incorporated as part of an economically viable “screen-and-treat” approach in the developing world. The manner in which vaccination and screening programs are integrated will need to be considered carefully so that they are efficient in reducing the overall incidence of cervical cancer as reported by Lowy et al. (Cancer 113:1980–1993, 2008).

Keywords

Phosphorus Europe Adenocarcinoma Recombination Iodine 

References

  1. Agnantis NJ, Sotiriadis A, Paraskevaidis E (2003) The current status of HPV DNA testing. Eur J Gynaecol Oncol 24:351–356PubMedGoogle Scholar
  2. Agorastos T, Sotiriadis A, Chatzigeorgiou K (2010) Can HPV testing replace the pap smear? Ann N Y Acad Sci 1205:51–56PubMedCrossRefGoogle Scholar
  3. Amortegui AJ, Meyer MP (1990) In-situ hybridization for the diagnosis and typing of human papillomavirus. Clin Biochem 23:301–306PubMedCrossRefGoogle Scholar
  4. Apgar BS, Brotzman G (1999) HPV testing in the evaluation of the minimally abnormal Papanicolaou smear. Am Fam Physician 59:2794–2801PubMedGoogle Scholar
  5. Arbyn M, Cuzick J (2009) International agreement to join forces in synthesizing evidence on new methods for cervical cancer prevention. Cancer Lett 278:1–2PubMedCrossRefGoogle Scholar
  6. Arbyn M, Paraskevaidis E, Martin-Hirsch P et al (2005) 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 99:S7–S11PubMedCrossRefGoogle Scholar
  7. Arbyn M, Sasieni P, Meijer CJ et al (2006) Clinical applications of HPV testing: a summary of meta-analyses. Vaccine 24(Suppl 3):S78–S89, Chapter 9CrossRefGoogle Scholar
  8. Arbyn M, Martin-Hirsch P, Buntinx F et al (2009) Triage of women with equivocal or low-grade cervical cytology results: a meta-analysis of the HPV test positivity rate. J Cell Mol Med 13:648–659PubMedCrossRefGoogle Scholar
  9. Austin RM (2003) Human papillomavirus reporting: minimizing patient and laboratory risk. Arch Pathol Lab Med 127:973–977PubMedGoogle Scholar
  10. Avrich E, Sulik S, Nashelsky J (2006) What is the appropriate management for a patient with CIN1 on colposcopy? J Fam Pract 55:145–146PubMedGoogle Scholar
  11. Belinson SE, Belinson JL (2010) Human papillomavirus DNA testing for cervical cancer screening: practical aspects in developing countries. Mol Diagn Ther 14:215–222PubMedGoogle Scholar
  12. Bollmann R (2001) DNA-cytometry in dysplasias of the uterine cervix. Zentralbl Gynakol 123:206–210PubMedCrossRefGoogle Scholar
  13. Burd EM (2003) Human papillomavirus and cervical cancer. Clin Microbiol Rev 16:1–17PubMedCrossRefGoogle Scholar
  14. Burger EA, Kornør H, Klemp M et al (2011) HPV mRNA tests for the detection of cervical intraepithelial neoplasia: a systematic review. Gynecol Oncol 120:430–438PubMedCrossRefGoogle Scholar
  15. Carcopino X, Henry M, Olive D et al (2011) Detection and quantification of human papillomavirus genital infections: virological, epidemiological, and clinical applications. Med Mal Infect 41:68–79PubMedCrossRefGoogle Scholar
  16. Castle PE (2009) The evolving definition of carcinogenic human papillomavirus. Infect Agent Cancer 4:7PubMedCrossRefGoogle Scholar
  17. Coutlée F, Mayrand MH, Provencher D et al (1997) The future of HPV testing in clinical laboratories and applied virology research. Clin Diagn Virol 8:123–141PubMedCrossRefGoogle Scholar
  18. Cox JT (1996) Clinical role of HPV testing. Obstet Gynecol Clin North Am 23:811–851PubMedCrossRefGoogle Scholar
  19. Cox JT (2006) The development of cervical cancer and its precursors: what is the role of human papillomavirus infection? Curr Opin Obstet Gynecol 18(Suppl 1):s5–s13PubMedCrossRefGoogle Scholar
  20. Cox JT (2009) History of the use of HPV testing in cervical screening and in the management of abnormal cervical screening results. J Clin Virol 45(Suppl 1):S3–S12PubMedCrossRefGoogle Scholar
  21. Cox JT, American Society for Colposcopy and Cervical Pathology (2003) The clinician’s view: role of human papillomavirus testing in the American society for colposcopy and cervical pathology guidelines for the management of abnormal cervical cytology and cervical cancer precursors. Arch Pathol Lab Med 127:950–958PubMedGoogle Scholar
  22. Cronjé HS (2004) Screening for cervical cancer in developing countries. Int J Gynaecol Obstet 84:101–108PubMedCrossRefGoogle Scholar
  23. Crosbie EJ, Kitchener HC (2006) Human papillomavirus in cervical screening and vaccination. Clin Sci (Lond) 110:543–552CrossRefGoogle Scholar
  24. Crum CP, Barber S, Roche JK (1991) Pathobiology of papillomavirus-related cervical diseases: prospects for immunodiagnosis. Clin Microbiol Rev 4:270–285PubMedGoogle Scholar
  25. Crum CP, Abbott DW, Quade BJ (2003) Cervical cancer screening: from the Papanicolaou smear to the vaccine era. J Clin Oncol 21:224s–230sPubMedCrossRefGoogle Scholar
  26. Cuschieri KS, Cubie HA (2005) The role of human papillomavirus testing in cervical screening. J Clin Virol 32(Suppl 1):S34–S42PubMedCrossRefGoogle Scholar
  27. Cuzick J, Arbyn M, Sankaranarayanan R (2008) Overview of human papillomavirus-based and other novel options for cervical cancer screening in developed and developing countries. Vaccine 26(Suppl 10):K29–K41PubMedCrossRefGoogle Scholar
  28. Davey DD, Greenspan DL, Kurtycz DF et al (2010) Atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion: review of ancillary testing modalities and implications for follow-up. J Low Genit Tract Dis 14:206–214PubMedCrossRefGoogle Scholar
  29. Doorbar J, Cubie H (2005) Molecular basis for advances in cervical screening. Mol Diagn 9:129–142PubMedCrossRefGoogle Scholar
  30. Douglas JM Jr, Werness BA (1989) Genital human papillomavirus infections. Clin Lab Med 9:421–444PubMedGoogle Scholar
  31. Drake M, Medley G, Mitchell H (1987) Cytologic detection of human papillomavirus infection. Obstet Gynecol Clin North Am 14:431–450PubMedGoogle Scholar
  32. Dürst M, Glitz D, Schneider A et al (1992) Human papillomavirus type 16 (HPV 16) gene expression and DNA replication in cervical neoplasia: analysis by in situ hybridization. Virology 189:132–140PubMedCrossRefGoogle Scholar
  33. Ferenczy A, Jenson AB (1996) Tissue effects and host response. The key to the rational triage of cervical neoplasia. Obstet Gynecol Clin North Am 23:759–782PubMedCrossRefGoogle Scholar
  34. Franco EL (2000) Statistical issues in human papillomavirus testing and screening. Clin Lab Med 20:345–367PubMedGoogle Scholar
  35. Franco EL (2003) Primary screening of cervical cancer with human papillomavirus tests. J Natl Cancer Inst Monogr 31:89–96, Chapter 13PubMedCrossRefGoogle Scholar
  36. Franco EL, Cuzick J (2008) Cervical cancer screening following prophylactic human papillomavirus vaccination. Vaccine 26(Suppl 1):A16–A23PubMedCrossRefGoogle Scholar
  37. Franco EL, Ferenczy A (2007) Cervical cancer screening following the implementation of prophylactic human papillomavirus vaccination. Future Oncol 3:319–327PubMedCrossRefGoogle Scholar
  38. Franco EL, Cuzick J, Hildesheim A et al (2006) Issues in planning cervical cancer screening in the era of HPV vaccination. Vaccine 24(Suppl 3):S171–S177, Chapter 20CrossRefGoogle Scholar
  39. Franco EL, Coutlée F, Ferenczy A (2009a) Integrating human papillomavirus vaccination in cervical cancer control programs. Public Health Genomics 12:352–361PubMedCrossRefGoogle Scholar
  40. Franco EL, Mahmud SM, Tota J et al (2009b) The expected impact of HPV vaccination on the accuracy of cervical cancer screening: the need for a paradigm change. Arch Med Res 40:478–485PubMedCrossRefGoogle Scholar
  41. Gissmann L, Boshart M, Dürst M et al (1984) Presence of human papillomavirus in genital tumors. J Invest Dermatol 83:26s–28sPubMedCrossRefGoogle Scholar
  42. Goldie SJ, Goldhaber-Fiebert JD, Garnett GP (2006a) Public health policy for cervical cancer prevention: the role of decision science, economic evaluation, and mathematical modeling. Vaccine 24(Suppl 3):S155–S163, Chapter 18CrossRefGoogle Scholar
  43. Goldie SJ, Kim JJ, Myers E (2006b) Cost-effectiveness of cervical cancer screening. Vaccine 24(Suppl 3):S164–S170, Chapter 19CrossRefGoogle Scholar
  44. Gray SH, Walzer TB (2004) New strategies for cervical cancer screening in adolescents. Curr Opin Pediatr 16:344–349PubMedCrossRefGoogle Scholar
  45. Grce M, Matovina M, Milutin-Gasperov N et al (2010) Advances in cervical cancer control and future perspectives. Coll Antropol 34:731–736PubMedGoogle Scholar
  46. Hillemanns P, Thaler C, Kimmig R (1997) Epidemiology and diagnosis of cervical intraepithelial neoplasia – is the present concept of screening and diagnosis still current? Gynakol Geburtshilfliche Rundsch 37:179–190PubMedCrossRefGoogle Scholar
  47. Hubbard RA (2003) Human papillomavirus testing methods. Arch Pathol Lab Med 127:940–945PubMedGoogle Scholar
  48. Huh W, Einstein MH, Herzog TJ et al (2010) What is the role of HPV typing in the United States now and in the next five years in a vaccinated population? Gynecol Oncol 117:481–485PubMedCrossRefGoogle Scholar
  49. Iftner T, Villa LL (2003) Human papillomavirus technologies. J Natl Cancer Inst Monogr 31:80–88, Chapter 12PubMedCrossRefGoogle Scholar
  50. Jin XW, Xu H (2001) Cervical cancer screening from Pap smear to human papillomavirus DNA testing. Compr Ther 27:202–208PubMedCrossRefGoogle Scholar
  51. Jin XW, Cash J, Kennedy AW (1999) Human papillomavirus typing and the reduction of cervical cancer risk. Cleve Clin J Med 66:533–539PubMedGoogle Scholar
  52. Kalof AN, Cooper K (2006) p16INK4a immunoexpression: surrogate marker of high-risk HPV and high-grade cervical intraepithelial neoplasia. Adv Anat Pathol 13:190–194PubMedCrossRefGoogle Scholar
  53. Kinney W, Stoler MH, Castle PE (2010) Special commentary: patient safety and the next generation of HPV DNA tests. Am J Clin Pathol 134:193–199PubMedCrossRefGoogle Scholar
  54. Kostopoulou E, Samara M, Kollia P et al (2011) Different patterns of p16 immunoreactivity in cervical biopsies: correlation to lesion grade and HPV detection, with a review of the literature. Eur J Gynaecol Oncol 32:54–61PubMedGoogle Scholar
  55. Kyrgiou M, Tsoumpou I, Vrekoussis T et al (2006) The up-to-date evidence on colposcopy practice and treatment of cervical intraepithelial neoplasia: the Cochrane colposcopy & cervical cytopathology collaborative group (C5 group) approach. Cancer Treat Rev 32:516–523PubMedCrossRefGoogle Scholar
  56. Kyrgiou M, Valasoulis G, Founta C et al (2010) Clinical management of HPV-related disease of the lower genital tract. Ann N Y Acad Sci 1205:57–68PubMedCrossRefGoogle Scholar
  57. Lancaster WD, Jenson AB (1987) Human papillomavirus infection and anogenital neoplasia: speculations for the future. Obstet Gynecol Clin North Am 14:601–609PubMedGoogle Scholar
  58. Levêque J, Classe JM, Marret H et al (2005) Contribution of viral typing in cytological anomalies of the cervix. J Gynecol Obstet Biol Reprod (Paris) 34:427–439Google Scholar
  59. Levine L, Lucci JA 3rd, Dinh TV (2003) Atypical glandular cells: new Bethesda terminology and management guidelines. Obstet Gynecol Surv 58:399–406PubMedGoogle Scholar
  60. Lörincz AT (1987) Detection of human papillomavirus infection by nucleic acid hybridization. Obstet Gynecol Clin North Am 14:451–469PubMedGoogle Scholar
  61. Lörincz AT, Richart RM (2003) Human papillomavirus DNA testing as an adjunct to cytology in cervical screening programs. Arch Pathol Lab Med 127:959–968PubMedGoogle Scholar
  62. Lynge E, Rebolj M (2009) Primary HPV screening for cervical cancer prevention: results from European trials. Nat Rev Clin Oncol 6:699–706PubMedCrossRefGoogle Scholar
  63. Lynge E, Antilla A, Arbyn M et al (2009) What’s next? Perspectives and future needs of cervical screening in Europe in the era of molecular testing and vaccination. Eur J Cancer 45:2714–2721PubMedCrossRefGoogle Scholar
  64. Malinowski DP (2005) Molecular diagnostic assays for cervical neoplasia: emerging markers for the detection of high-grade cervical disease. Biotechniques 38(Suppl):17–23CrossRefGoogle Scholar
  65. McDougall JK, Beckmann AM, Kiviat NB (1986) Methods for diagnosing papillomavirus infection. Ciba Found Symp 120:86–103PubMedGoogle Scholar
  66. Melchers WJ, Claas HC, Quint WG (1991) Use of the polymerase chain reaction to study the relationship between human papillomavirus infections and cervical cancer. Eur J Clin Microbiol Infect Dis 10:714–727PubMedCrossRefGoogle Scholar
  67. Mergui JL, Levêque J (2008) What kind of follow-up after surgical treatment for high-grade cervix lesion? Gynecol Obstet Fertil 36:441–447PubMedCrossRefGoogle Scholar
  68. Mergui JL, Polena V, David-Montefiore E et al (2008) Guidelines for the follow-up of women treated for high-grade cervical neoplasia. J Gynecol Obstet Biol Reprod (Paris) 37(Suppl 1):S121–S130Google Scholar
  69. Monsonego J (2004) Colposcopy: the value of HPV testing in clinical practice. Gynecol Obstet Fertil 32:62–74PubMedCrossRefGoogle Scholar
  70. Monsonego J (2007) Prevention of cervical cancer: screening, progress and perspectives. Presse Med 36:92–111PubMedCrossRefGoogle Scholar
  71. Moore KN, Walker JL (2004) High risk human papillomavirus testing: guidelines for use in screening, triage, and follow-up for the prevention and early detection of cervical cancer. J Natl Compr Canc Netw 2:589–596PubMedGoogle Scholar
  72. Morris BJ, Rose BR (2007) Cervical screening in the 21st century: the case for human papillomavirus testing of self-collected specimens. Clin Chem Lab Med 45:577–591PubMedCrossRefGoogle Scholar
  73. Moscicki AB (2003) Cervical cytology screening in teens. Curr Womens Health Rep 3:433–437PubMedGoogle Scholar
  74. Mühlberger N, Sroczynski G, Esteban E et al (2008) Cost-effectiveness of primarily human papillomavirus-based cervical cancer screening in settings with currently established Pap screening: a systematic review commissioned by the German federal ministry of health. Int J Technol Assess Health Care 24:184–192PubMedCrossRefGoogle Scholar
  75. Mulvany NJ, Allen DG, Wilson SM (2008) Diagnostic utility of p16INK4a: a reappraisal of its use in cervical biopsies. Pathology 40:335–344PubMedCrossRefGoogle Scholar
  76. Myers E, Huh WK, Wright JD et al (2008) The current and future role of screening in the era of HPV vaccination. Gynecol Oncol 109:S31–S39PubMedCrossRefGoogle Scholar
  77. Nayar R, Tabbara SO (2003) Atypical squamous cells: update on current concepts. Clin Lab Med 23:605–632PubMedCrossRefGoogle Scholar
  78. Nindl I, Greinke C, Zahm DM et al (1997) Human papillomavirus distribution in cervical tissues of different morphology as determined by hybrid capture assay and PCR. Int J Gynecol Pathol 16:197–204PubMedCrossRefGoogle Scholar
  79. Nowak JA (2000) Telomerase, cervical cancer, and human papillomavirus. Clin Lab Med 20:369–382PubMedGoogle Scholar
  80. O’Neill CJ, McCluggage WG (2006) p16 expression in the female genital tract and its value in diagnosis. Adv Anat Pathol 13:8–15PubMedCrossRefGoogle Scholar
  81. Ogilvie GS, Patrick DM, Schulzer M et al (2005) Diagnostic accuracy of self collected vaginal specimens for human papillomavirus compared to clinician collected human papillomavirus specimens: a meta-analysis. Sex Transm Infect 81:207–212PubMedCrossRefGoogle Scholar
  82. Pagliusi SR, Garland SM (2007) International standard reagents for HPV detection. Dis Markers 23:283–296PubMedGoogle Scholar
  83. Pagliusi SR, Dillner J, Pawlita M et al (2006) International standard reagents for harmonization of HPV serology and DNA assays – an update. Vaccine 24(Suppl 3):S193–S200, Chapter 23CrossRefGoogle Scholar
  84. Paraskevaidis E, Arbyn M, Sotiriadis A et al (2004) The role of HPV DNA testing in the follow-up period after treatment for CIN: a systematic review of the literature. Cancer Treat Rev 30:205–211PubMedCrossRefGoogle Scholar
  85. Petignat P, Faltin DL, Bruchim I et al (2007) Are self-collected samples comparable to physician-collected cervical specimens for human papillomavirus DNA testing? A systematic review and meta-analysis. Gynecol Oncol 105:530–535PubMedCrossRefGoogle Scholar
  86. Poljak M, Kocjan BJ (2010) Commercially available assays for multiplex detection of alpha human papillomaviruses. Expert Rev Anti Infect Ther 8:1139–1162PubMedCrossRefGoogle Scholar
  87. Rando RF (1990) Nucleic acid hybridization as a diagnostic tool for the detection of human papillomaviruses. Adv Exp Med Biol 263:89–109PubMedCrossRefGoogle Scholar
  88. Rapini RP (1990) Venereal warts. Prim Care 17:127–144PubMedGoogle Scholar
  89. Renshaw AA (2003) Rescreening in cervical cytology for quality control. When bad data is worse than no data or what works, what doesn’t, and why. Clin Lab Med 23:695–708PubMedCrossRefGoogle Scholar
  90. Richart RM, Wright TC Jr (1992) Human papillomavirus. Curr Opin Obstet Gynecol 4:662–669PubMedGoogle Scholar
  91. Richart RM, Masood S, Syrjänen KJ et al (1998) Human papillomavirus. International academy of cytology task force summary. Diagnostic cytology towards the 21st century: an international expert conference and tutorial. Acta Cytol 42:50–58PubMedCrossRefGoogle Scholar
  92. Riethmuller D, Ramanah R, Pretet JL (2008) Integrating HPV testing for primary screening? J Gynecol Obstet Biol Reprod (Paris) 37(Suppl 1):S139–S151Google Scholar
  93. Roman A, Fife KH (1989) Human papillomaviruses: are we ready to type? Clin Microbiol Rev 2:166–190PubMedGoogle Scholar
  94. Ronco G (1999) Use of molecular tests of human papilloma virus (HPV) as screening test for cervix cancer: a review. Epidemiol Prev 23:372–377PubMedGoogle Scholar
  95. Ronco G, Giorgi Rossi P (2008) New paradigms in cervical cancer prevention: opportunities and risks. BMC Womens Health 8:23PubMedCrossRefGoogle Scholar
  96. Sankaranarayanan R, Gaffikin L, Jacob M et al (2005) A critical assessment of screening methods for cervical neoplasia. Int J Gynaecol Obstet 89(Suppl 2):S4–S12PubMedCrossRefGoogle Scholar
  97. Sawchuk WS (1991) Ancillary diagnostic tests for detection of human papillomavirus infection. Dermatol Clin 9:277–286PubMedGoogle Scholar
  98. Scarinci IC, Garcia FA, Kobetz E et al (2010) Cervical cancer prevention: new tools and old barriers. Cancer 116:2531–2542PubMedGoogle Scholar
  99. Schiffman MH (1992) Validation of hybridization assays: correlation of filter in situ, dot blot and PCR with Southern blot. IARC Sci Publ 119:169–179PubMedGoogle Scholar
  100. Schiffman M, Wentzensen N, Wacholder S et al (2011) Human papillomavirus testing in the prevention of cervical cancer. J Natl Cancer Inst 103:368–383PubMedCrossRefGoogle Scholar
  101. Schmeink CE, Bekkers RL, Massuger LF et al (2011) The potential role of self-sampling for high-risk human papillomavirus detection in cervical cancer screening. Rev Med Virol 21:139–153PubMedCrossRefGoogle Scholar
  102. Schneider A, Meinhardt G, De-Villiers EM et al (1987) Sensitivity of the cytologic diagnosis of cervical condyloma in comparison with HPV-DNA hybridization studies. Diagn Cytopathol 3:250–255PubMedCrossRefGoogle Scholar
  103. Sehgal A, Gupta S, Parashari A et al (2009) Urine HPV-DNA detection for cervical cancer screening: prospects and prejudices. J Obstet Gynaecol 29:583–589PubMedCrossRefGoogle Scholar
  104. Sharpless KE, O’Sullivan DM, Schnatz PF (2009) The utility of human papillomavirus testing in the management of atypical glandular cells on cytology. J Low Genit Tract Dis 13:72–78PubMedCrossRefGoogle Scholar
  105. Sherman ME, Kurman RJ (1996) The role of exfoliative cytology and histopathology in screening and triage. Obstet Gynecol Clin North Am 23:641–655PubMedGoogle Scholar
  106. Soler ME, Blumenthal PD (2000) New technologies in cervical cancer precursor detection. Curr Opin Oncol 12:460–465PubMedCrossRefGoogle Scholar
  107. Solomon D (2003) Role of triage testing in cervical cancer screening. J Natl Cancer Inst Monogr 31:97–101, Chapter 14PubMedCrossRefGoogle Scholar
  108. Spitzer M (2007) Screening and management of women and girls with human papillomavirus infection. Gynecol Oncol 107:S14–S18PubMedCrossRefGoogle Scholar
  109. Stewart DE, Gagliardi A, Johnston M et al (2007) Self-collected samples for testing of oncogenic human papillomavirus: a systematic review. J Obstet Gynaecol Can 29:817–828PubMedGoogle Scholar
  110. Stillman MJ, Day SP, Schutzbank TE (2009) A comparative review of laboratory-developed tests utilizing Invader HPV analyte-specific reagents for the detection of high-risk human papillomavirus. J Clin Virol 45(Suppl 1):S73–S77PubMedCrossRefGoogle Scholar
  111. Subramanya D, Grivas PD (2008) HPV and cervical cancer: updates on an established relationship. Postgrad Med 120:7–13PubMedCrossRefGoogle Scholar
  112. Swygart C (1997) Human papillomavirus: disease and laboratory diagnosis. Br J Biomed Sci 54:299–303PubMedGoogle Scholar
  113. Syrjänen KJ (2005) Immunohistochemistry in assessment of molecular pathogenesis of cervical carcinogenesis. Eur J Gynaecol Oncol 26:5–19PubMedGoogle Scholar
  114. Syrjänen K, Di Bonito L, Gonçalves L et al (2010) Cervical cancer screening in Mediterranean countries: implications for the future. Cytopathology 21:359–367PubMedCrossRefGoogle Scholar
  115. Tiro JA, Saraiya M, Jain N et al (2008) Human papillomavirus and cervical cancer behavioral surveillance in the US. Cancer 113:3013–3030PubMedCrossRefGoogle Scholar
  116. Tota J, Mahmud SM, Ferenczy A (2010) Promising strategies for cervical cancer screening in the post-human papillomavirus vaccination era. Sex Health 7:376–382PubMedCrossRefGoogle Scholar
  117. Tsoumpou I, Arbyn M, Kyrgiou M et al (2009) p16(INK4a) immunostaining in cytological and histological specimens from the uterine cervix: a systematic review and meta-analysis. Cancer Treat Rev 35:210–220PubMedCrossRefGoogle Scholar
  118. van Oortmarssen GJ, Boer R, Habbema JD (1995) Modelling issues in cancer screening. Stat Methods Med Res 4:33–54PubMedCrossRefGoogle Scholar
  119. Varras M (2004) The problems with different management options of women with minor squamous intraepithelial lesions in Pap tests. Clin Exp Obstet Gynecol 31:249–250PubMedGoogle Scholar
  120. von Knebel DM (2001b) New molecular tools for efficient screening of cervical cancer. Dis Markers 17:123–128Google Scholar
  121. von Knebel Doeberitz M (2001a) Aspects of molecular pathogenesis of cervical cancer in establishing new tumor markers for early detection and diagnosis. Zentralbl Gynakol 123:186–191CrossRefGoogle Scholar
  122. Whiteside MA, Siegel EM, Unger ER (2008) Human papillomavirus and molecular considerations for cancer risk. Cancer 113:2981–2994PubMedCrossRefGoogle Scholar
  123. Wick MJ (2000) Diagnosis of human papillomavirus gynecologic infections. Clin Lab Med 20:271–287PubMedGoogle Scholar
  124. Wilbur DC (2003) Cervical cytology automation: an update for 2003. The end of the quest nears? Clin Lab Med 23:755–774PubMedCrossRefGoogle Scholar
  125. Wiwanitkit V (2009) Screening for cervical cancer: which common technique is the most cost-effective choice? Asian Pac J Cancer Prev 10:531–532PubMedGoogle Scholar
  126. Wright TC Jr (2007) Cervical cancer screening in the 21st century: is it time to retire the PAP smear? Clin Obstet Gynecol 50:313–323PubMedCrossRefGoogle Scholar
  127. Wright TC Jr, Bosch FX (2008) Is viral status needed before vaccination? Vaccine 26(Suppl 1):A12–A15PubMedCrossRefGoogle Scholar
  128. Wright TC Jr, Cox JT, Massad LS et al (2002) 2001 consensus guidelines for the management of women with cervical cytological abnormalities. JAMA 287:2120–2129PubMedCrossRefGoogle Scholar
  129. Wright TC Jr, Schiffman M, Solomon D et al (2004) Interim guidance for the use of human papillomavirus DNA testing as an adjunct to cervical cytology for screening. Obstet Gynecol 103:304–309PubMedCrossRefGoogle Scholar
  130. Wright TC Jr, Massad LS, Dunton CJ et al (2007) 2006 consensus guidelines for the management of women with abnormal cervical cancer screening tests. Am J Obstet Gynecol 197:346–355PubMedCrossRefGoogle Scholar
  131. Yildiz IZ, Usubütün A, Firat P et al (2007) Efficiency of immunohistochemical p16 expression and HPV typing in cervical squamous intraepithelial lesion grading and review of the p16 literature. Pathol Res Pract 203:445–449PubMedCrossRefGoogle Scholar
  132. Zielinski GD, Bais AG, Helmerhorst TJ et al (2004) HPV testing and monitoring of women after treatment of CIN 3: review of the literature and meta-analysis. Obstet Gynecol Surv 59:543–553PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Division of Obstetrics and GynecologyCity HospitalPratoItaly
  2. 2.Centre Hospitalier Princesse GracePrincipality of MonacoMonaco

Personalised recommendations