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The Basic Elements of a Correct Diagnosis: From Cytohistopathology to Screening

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HPV and Cervical Cancer

Abstract

Although most women infected with the Human Papillomavirus (HPV) become negative within 2 years, women with persistent high-risk (HR) infections are at greatest risk for developing cervical cancer. Since the identification of HPV as the necessary cause of cervical cancer, HPV-based technology has become the center of novel primary and secondary cervical cancer prevention strategies by the introduction of HPV testing in screening and of HPV vaccines in preadolescent girls and young women. If implemented widely and wisely, the deployment of these protocols has the potential to complete Papanicolaou’s goal of cervical cancer eradication by extending the benefits of prevention to the developing populations of the world as reported by Castellsagué (Gynecol Oncol 110:S4–S7, 2008).

Even in the era of highly effective HPV prophylactic vaccines, substantial reduction in worldwide cervical cancer mortality will only be realized if effective early detection and treatment of the millions of women already infected. The millions who may not receive vaccination in the next decade can be broadly implemented through sustainable cervical cancer screening programs. Effective programs must meet three targets: (1) at least 70% of the targeted population should be screened at least once in a lifetime, (2) screening assays and diagnostic tests must be reproducible and sufficiently sensitive and specific for the detection of high-grade (HG) precursor lesions (i.e. cervical intraepithelial neoplasia, CIN2+), and 3) effective treatment must be provided. Efforts to increase the affordability and availability of HPV deoxy-ribonucleic acid (DNA) tests, community education and awareness, development of strong partnerships between community advocacy groups, health care centers and regional or local laboratories, and resource-appropriate strategies to identify and treat screen-positive women should now be prioritized to ensure successful public health translation of the technologic advancements in cervical cancer prevention as reported by Gravitt et al. (Int J Cancer 129:517–527, 2011).

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References

  • Agnantis NJ, Sotiriadis A, Paraskevaidis E (2003) The current status of HPV DNA testing. Eur J Gynaecol Oncol 24:351–356

    PubMed  CAS  Google Scholar 

  • Allen SM (1996) Cervical intraepithelial neoplasia: false negative smears. Br J Biomed Sci 53:152–156

    PubMed  CAS  Google Scholar 

  • Apgar BS, Brotzman G (1999) HPV testing in the evaluation of the minimally abnormal Papanicolaou smear. Am Fam Physician 59:2794–2801

    PubMed  CAS  Google Scholar 

  • Barrasso R (1992) Colposcopic diagnosis of HPV cervical lesions. IARC Sci Publ 119:67–74

    PubMed  Google Scholar 

  • Belinson SE, Belinson JL (2010) Human papillomavirus DNA testing for cervical cancer screening: practical aspects in developing countries. Mol Diagn Ther 14:215–222

    PubMed  Google Scholar 

  • Bernard HU (2005) The clinical importance of the nomenclature, evolution and taxonomy of human papillomaviruses. J Clin Virol 32(Suppl 1):S1–S6

    Article  PubMed  Google Scholar 

  • Breitenecker G, Gitsch G (1992) What’s new in diagnosis and treatment of HPV-associated cervical lesions. Pathol Res Pract 188:242–247

    Article  PubMed  CAS  Google Scholar 

  • Brink AA, Snijders PJ, Meijer CJ et al (2006) HPV testing in cervical screening. Best Pract Res Clin Obstet Gynaecol 20:253–266

    Article  PubMed  Google Scholar 

  • Broso PR, Buffetti G (1993) The Papanicolaou classification in the Bethesda system (National Cancer Institute, Bethesda, Maryland). Minerva Ginecol 45:557–563

    PubMed  CAS  Google Scholar 

  • Burger EA, Kornør H, Klemp M et al (2011) HPV mRNA tests for the detection of cervical intraepithelial neoplasia: a systematic review. Gynecol Oncol 120:430–438

    Article  PubMed  CAS  Google Scholar 

  • Castle PE (2009) The evolving definition of carcinogenic human papillomavirus. Infect Agent Cancer 4:7

    Article  PubMed  Google Scholar 

  • Coppleson M, Dalrymple JC, Atkinson KH (1993) Colposcopic differentiation of abnormalities arising in the transformation zone. Obstet Gynecol Clin North Am 20:83–110

    PubMed  CAS  Google Scholar 

  • Coutlée F, Mayrand MH, Roger M et al (2009) Detection and typing of human papillomavirus nucleic acids in biological fluids. Public Health Genomics 12:308–318

    Article  PubMed  Google Scholar 

  • Cox JT (2006) Human papillomavirus testing in primary cervical screening and abnormal Papanicolaou management. Obstet Gynecol Surv 61:S15–S25

    Article  PubMed  Google Scholar 

  • 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–S12

    Article  PubMed  Google Scholar 

  • Cronjé HS (2004) Screening for cervical cancer in developing countries. Int J Gynaecol Obstet 84:101–108

    Article  PubMed  Google Scholar 

  • Crum CP, Barber S, Roche JK (1991) Pathobiology of papillomavirus-related cervical diseases: prospects for immunodiagnosis. Clin Microbiol Rev 4:270–285

    PubMed  CAS  Google Scholar 

  • Crum CP, Abbott DW, Quade BJ (2003) Cervical cancer screening: from the Papanicolaou smear to the vaccine era. J Clin Oncol 21:224s–230s

    Article  PubMed  Google Scholar 

  • Cuschieri K, Wentzensen N (2008) Human papillomavirus mRNA and p16 detection as biomarkers for the improved diagnosis of cervical neoplasia. Cancer Epidemiol Biomarkers Prev 17:2536–2545

    Article  PubMed  CAS  Google Scholar 

  • Cuzick J, Arbyn M, Sankaranarayanan R et al (2008) Overview of human papillomavirus-based and other novel options for cervical cancer screening in developed and developing countries. Vaccine 26(Suppl 10):K29–K41

    Article  PubMed  Google Scholar 

  • 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 14:206–214

    Article  PubMed  Google Scholar 

  • Dewar MA, Hall K, Perchalski J (1992) Cervical cancer screening. Past success and future challenge. Prim Care 19:589–606

    PubMed  CAS  Google Scholar 

  • Doorbar J, Cubie H (2005) Molecular basis for advances in cervical screening. Mol Diagn 9:129–142

    Article  PubMed  Google Scholar 

  • Franco EL (2003) Primary screening of cervical cancer with human papillomavirus tests. J Natl Cancer Inst Monogr 31:89–96, Chapter 13

    Article  PubMed  Google Scholar 

  • Galloway DA (1992) Serological assays for the detection of HPV antibodies. IARC Sci Publ 119:147–161

    PubMed  Google Scholar 

  • García-Tamayo J, Molina J, Blasco-Olaetxea E (2009) Importance of immunohistochemical studies in the diagnosis and the prognostic evaluation of cervical intraepithelial neoplasia and invasive squamous cell carcinoma of the uterine cervix. Rev Invest Clin 50:241–250

    Google Scholar 

  • Greenberg MD, Campion MJ, Rutledge LH (1993) Cervicography as an adjunct to cytologic screening. Obstet Gynecol Clin North Am 20:13–29

    PubMed  CAS  Google Scholar 

  • Grubisić G, Klarić P, Jokanović L et al (2009) Diagnostic approach for precancerous and early invasive cancerous lesions of the uterine cervix. Coll Antropol 33:1431–1436

    PubMed  Google Scholar 

  • Holcomb K, Runowicz CD (2005) Cervical cancer screening. Surg Oncol Clin N Am 14:777–797

    Article  PubMed  Google Scholar 

  • Hubbard RA (2003) Human papillomavirus testing methods. Arch Pathol Lab Med 127:940–945

    PubMed  CAS  Google Scholar 

  • Keating JT, Ince T, Crum CP (2001) Surrogate biomarkers of HPV infection in cervical neoplasia screening and diagnosis. Adv Anat Pathol 8:83–92

    Article  PubMed  CAS  Google Scholar 

  • Kinney W, Stoler MH, Castle PE (2010) Special commentary: patient safety and the next generation of HPV DNA tests. Am J Clin Pathol 134:193–199

    Article  PubMed  Google Scholar 

  • Kiviat NB, Critchlow CW, Kurman RJ (1992) Reassessment of the morphological continuum of cervical intraepithelial lesions: does it reflect different stages in the progression to cervical carcinoma? IARC Sci Publ 119:59–66

    PubMed  Google Scholar 

  • Klug SJ, Ressing M, Koenig J et al (2009) TP53 codon 72 polymorphism and cervical cancer: a pooled analysis of individual data from 49 studies. Lancet Oncol 10:772–784

    Article  PubMed  CAS  Google Scholar 

  • 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 32:54–61

    PubMed  CAS  Google Scholar 

  • 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 32:516–523

    Article  PubMed  CAS  Google Scholar 

  • Libra M, Scalisi A, Vella N et al (2009) Uterine cervical carcinoma: role of matrix metalloproteinases (review). Int J Oncol 34:897–903

    PubMed  CAS  Google Scholar 

  • Lörincz AT (1996) Molecular methods for the detection of human papillomavirus infection. Obstet Gynecol Clin North Am 23:707–730

    Article  PubMed  Google Scholar 

  • Lörincz AT, Richart RM (2003) Human papillomavirus DNA testing as an adjunct to cytology in cervical screening programs. Arch Pathol Lab Med 127:959–968

    PubMed  Google Scholar 

  • Lynge E, Rebolj M (2009) Primary HPV screening for cervical cancer prevention: results from European trials. Nat Rev Clin Oncol 6:699–706

    Article  PubMed  Google Scholar 

  • Malinowski DP (2005) Molecular diagnostic assays for cervical neoplasia: emerging markers for the detection of high-grade cervical disease. Biotechniques (Suppl):17–23

    Google Scholar 

  • 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 10:714–727

    Article  PubMed  CAS  Google Scholar 

  • Miller KE, Losh DP, Folley A (1992) Evaluation and follow-up of abnormal Pap smears. Am Fam Physician 45:143–150

    PubMed  CAS  Google Scholar 

  • Mitchell MF, Cantor SB, Brookner C et al (1999a) Screening for squamous intraepithelial lesions with fluorescence spectroscopy. Obstet Gynecol 94:889–896

    Article  PubMed  CAS  Google Scholar 

  • Mitchell MF, Cantor SB, Ramanujam N et al (1999b) Fluorescence spectroscopy for diagnosis of squamous intraepithelial lesions of the cervix. Obstet Gynecol 93:462–470

    Article  PubMed  CAS  Google Scholar 

  • Monsonego J (2007) Prevention of cervical cancer: screening, progress and perspectives. Presse Med 36:92–111

    Article  PubMed  Google Scholar 

  • 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 2:589–596

    PubMed  Google Scholar 

  • Morris BJ (2005) Cervical human papillomavirus screening by PCR: advantages of targeting the E6/E7 region. Clin Chem Lab Med 43:1171–1177

    Article  PubMed  CAS  Google Scholar 

  • 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 45:577–591

    Article  PubMed  CAS  Google Scholar 

  • Mossetti C, Remotti G, Marchionni M et al (1989) Assessment of human papilloma virus colposcopic findings of the cervix (in the Italian colposcopic classification). Minerva Ginecol 41:251–256

    PubMed  CAS  Google Scholar 

  • Mulvany NJ, Allen DG, Wilson SM (2008) Diagnostic utility of p16INK4a: a reappraisal of its use in cervical biopsies. Pathology 40:335–344

    Article  PubMed  CAS  Google Scholar 

  • Nayar R, Tabbara SO (2003) Atypical squamous cells: update on current concepts. Clin Lab Med 23:605–632

    Article  PubMed  Google Scholar 

  • Nguyen HN, Nordqvist SR (1999) The Bethesda system and evaluation of abnormal pap smears. Semin Surg Oncol 16:217–221

    Article  PubMed  CAS  Google Scholar 

  • Nijhuis ER, Reesink-Peters N, Wisman GB et al (2006) An overview of innovative techniques to improve cervical cancer screening. Cell Oncol 28:233–246

    PubMed  Google Scholar 

  • Nowak JA (2000) Telomerase, cervical cancer, and human papillomavirus. Clin Lab Med 20:369–382

    PubMed  CAS  Google Scholar 

  • Perlman SE (1999) Pap smears: screening, interpretation, treatment. Adolesc Med 10:243–254

    PubMed  CAS  Google Scholar 

  • Peroni M, Visci P (2000) Colposcopy in human papilloma virus infections of the distal uro-ano-genital tract. Minerva Ginecol 52:59–67

    PubMed  CAS  Google Scholar 

  • Poljak M, Kocjan BJ (2010) Commercially available assays for multiplex detection of alpha human papillomaviruses. Expert Rev Anti Infect Ther 8:1139–1162

    Article  PubMed  CAS  Google Scholar 

  • Prendiville W (2005) Recent innovations in colposcopy practice. Best Pract Res Clin Obstet Gynaecol 19:779–792

    Article  PubMed  Google Scholar 

  • Ronco G (1999) Use of molecular tests of human papilloma virus (HPV) as screening test for cervix cancer: a review. Epidemiol Prev 23:372–377

    PubMed  CAS  Google Scholar 

  • 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–S12

    Article  PubMed  Google Scholar 

  • Schiffman MH (1992) Validation of hybridization assays: correlation of filter in situ, dot blot and PCR with Southern blot. IARC Sci Publ 119:169–179

    PubMed  Google Scholar 

  • Schneider V (2003) Symposium part 2: Should the Bethesda System terminology be used in diagnostic surgical pathology?: Counterpoint. Int J Gynecol Pathol 22:13–17

    Article  PubMed  Google Scholar 

  • Shah KV (1992) Human papillomaviruses and other biological markers in cervical cancer. IARC Sci Publ 119:209–218

    PubMed  Google Scholar 

  • Sherman ME, Kurman RJ (1996) The role of exfoliative cytology and histopathology in screening and triage. Obstet Gynecol Clin North Am 23:641–655

    PubMed  CAS  Google Scholar 

  • Solomon D (2003) Role of triage testing in cervical cancer screening. J Natl Cancer Inst Monogr 31:97–101, Chapter 14

    Article  PubMed  Google Scholar 

  • Sousa H, Santos AM, Pinto D et al (2007) Is the p53 codon 72 polymorphism a key biomarker for cervical cancer development? A meta-analysis review within European populations. Int J Mol Med 20:731–741

    PubMed  CAS  Google Scholar 

  • 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–S77

    Article  PubMed  CAS  Google Scholar 

  • Swygart C (1997) Human papillomavirus: disease and laboratory diagnosis. Br J Biomed Sci 54:299–303

    PubMed  CAS  Google Scholar 

  • Syrjänen KJ (2005) Immunohistochemistry in assessment of molecular pathogenesis of cervical carcinogenesis. Eur J Gynaecol Oncol 26:5–19

    PubMed  Google Scholar 

  • Syrjänen K, Di Bonito L, Gonçalves L et al (2010) Cervical cancer screening in Mediterranean countries: implications for the future. Cytopathology 21:359–367

    Article  PubMed  Google Scholar 

  • 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 35:210–220

    Article  PubMed  CAS  Google Scholar 

  • Velazquez Torres A, Gariglio Vidal P (2002) Possible role of transcription factor AP1 in the tissue-specific regulation of human papillomavirus. Rev Invest Clin 54:231–242

    PubMed  Google Scholar 

  • Ventura G, Di Girolamo L, Ventura GC (1990) Cellular dyskeratosis as predictive factor in condylomatosis histologically confirmed by biopsy. Minerva Ginecol 42:503–506

    PubMed  CAS  Google Scholar 

  • von Knebel DM (2001a) Aspects of molecular pathogenesis of cervical cancer in establishing new tumor markers for early detection and diagnosis. Zentralbl Gynakol 123:186–191

    Article  Google Scholar 

  • von Knebel DM (2001b) New molecular tools for efficient screening of cervical cancer. Dis Markers 17:123–128

    Google Scholar 

  • Wentzensen N, Sherman ME, Schiffman M et al (2009) Utility of methylation markers in cervical cancer early detection: appraisal of the state-of-the-science. Gynecol Oncol 112:293–299

    Article  PubMed  CAS  Google Scholar 

  • Wright TC Jr (2007) Cervical cancer screening in the 21st century: is it time to retire the PAP smear? Clin Obstet Gynecol 50:313–323

    Article  PubMed  Google Scholar 

  • 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 103:304–309

    Article  PubMed  Google Scholar 

  • Zaravinos A, Mammas IN, Sourvinos G et al (2009) Molecular detection methods of human papillomavirus (HPV). Int J Biol Markers 24:215–222

    PubMed  CAS  Google Scholar 

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Correspondence to Ciro Comparetto .

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Borruto, F., Comparetto, C. (2012). The Basic Elements of a Correct Diagnosis: From Cytohistopathology to Screening. In: Borruto, F., De Ridder, M. (eds) HPV and Cervical Cancer. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-1988-4_5

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