[en] AIMS: Cervical screening, currently performed by cervical cytology, depends on the timely detection of malignant lesions for its success. The presence of high-risk human papillomavirus (hrHPV) is associated with an increased risk of subsequent high-grade cervical intra-epithelial neoplasia (CIN2/3) and cervical cancer. The aim of this study was to determine the extent to which hrHPV is present in cervical smears with a high a priori chance of being false negative (ie, in normal smears preceding CIN2/3). METHODS: Archival specimens of 187 women with CIN2/3 and preceding normal conventional smears were identified retrospectively. Of these specimens, 144 (77%) had adequate cytological samples for further HPV DNA testing. RESULTS: Of 144 CIN2/3 lesions, preceding normal smears showed hrHPV positivity in 80% of cases. Of the hrHPV-positive smears, 69% were upgraded cytologically at rescreening compared with 24% of hrHPV-negative smears (p<0.001). Upgrading of smears was not associated with specific hrHPV types (p = 0.217). In over 90% of cases, type concordance in smear and CIN2/3 lesion was demonstrated. CONCLUSIONS: hrHPV is present in a high proportion of normal archival smears preceding CIN2/3, and false-negative cytology was highly associated with the presence of hrHPV. This supports the current notion that hrHPV testing can be used as a primary cervical screening tool. If so, hrHPV-positive cervical smears should be carefully examined for cytological abnormalities to reduce false-negative cervical cytology.
Disciplines :
Genetics & genetic processes
Author, co-author :
BULK, Saskia ; Centre Hospitalier Universitaire de Liège - CHU > Génétique
Rozendaal, L.
Zielinski, G. D.
Berkhof, J.
Daalmeijer, N. C. Fransen
Snijders, P. J. F.
van Kemenade, F. J.
Meijer, C. J. L. M.
Language :
English
Title :
High-risk human papillomavirus is present in cytologically false-negative smears: an analysis of "normal" smears preceding CIN2/3.
scite shows how a scientific paper has been cited by providing the context of the citation, a classification describing whether it supports, mentions, or contrasts the cited claim, and a label indicating in which section the citation was made.
Bibliography
Walboomers JM, Jacobs MV, Manos MM, et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol 1999;189:12-9.
Cuzick J, Clavel C, Petry KU, et al. Overview of the European and North American studies on HPV testing in primary cervical cancer screening. Int J Cancer 2006;119:1095-101.
Bulkmans NW, Rozendaal L, Snijders PJ, et al. POBASCAM, a population-based randomized controlled trial for implementation of high-risk HPV testing in cervical screening: design, methods and baseline data of 44,102 women. Int J Cancer 2004;110:94-101.
Clifford GM, Gallus S, Herrero R, et al. Worldwide distribution of human papillomavirus types in cytologically normal women in the International Agency for Research on Cancer HPV prevalence surveys: a pooled analysis. Lancet 2005;366:991-8.
Cuzick J, Szarewski A, Cubie H, et al. Management of women who test positive for high-risk types of human papillomavirus: the HART study. Lancet 2003;362:1871-6.
Brink AA, Zielinski GD, Steenbergen RD, et al. Clinical relevance of human papillomavirus testing in cytopathology. Cytopathology 2005;16:7-12.
Kitchener HC, Almonte M, Wheeler P, et al. HPV testing in routine cervical screening: cross sectional data from the ARTISTIC trial. Br J Cancer 2006;95:56-61.
Ronco G, Cuzick J, Pierotti P, et al. Accuracy of liquid based versus conventional cytology: overall results of new technologies for cervical cancer screening randomised controlled trial. BMJ 2007;335:28.
Ylitalo N, Josefsson A, Melbye M, et al. A prospective study showing long-term infection with human papillomavirus 16 before the development of cervical carcinoma in situ. Cancer Res 2000;60:6027-32.
Zielinski GD, Snijders PJ, Rozendaal L, et al. HPV presence precedes abnormal cytology in women developing cervical cancer and signals false negative smears. Br J Cancer 2001;85:398-404.
van der GY, Molijn A, Doornewaard H, et al. Human papillomavirus and the long-term risk of cervical neoplasia. Am J Epidemiol 2002;156:158-64.
Wallin KL, Wiklund F, Angstrom T, et al. Type-specific persistence of human papillomavirus DNA before the development of invasive cervical cancer. N Engl J Med 1999;341:1633-8.
Stoler MH, Schiffman M. Interobserver reproducibility of cervical cytologic and histologic interpretations: realistic estimates from the ASCUS-LSIL Triage Study. JAMA 2001;285:1500-5.
van Ballegooijen M, Hermens R. Cervical cancer screening in the Netherlands. Eur J Cancer 2000;36:2244-6.
Anderson MC. Premalignant and malignant squamous lesions of the cervix. In: Fox H, Wells M, Haines, Taylor, eds. Obstetrical and gynaecological pathology. New York: Churchill Livingstone, 1995:292-7.
Bulk S, van Kemenade FJ, Rozendaal L, et al. The Dutch CISOE-A framework for cytology reporting increases efficacy of screening upon standardisation since 1996. J Clin Pathol 2004;57:388-93.
Solomon D, Davey D, Kurman R, et al. The 2001 Bethesda System: terminology for reporting results of cervical cytology. JAMA 2002;287:2114-9.
Jacobs MV, Snijders PJ, van den Brule AJ, et al. A general primer GP5+/GP6(+)-mediated PCR-enzyme immunoassay method for rapid detection of 14 high-risk and 6 low-risk human papillomavirus genotypes in cervical scrapings. J Clin Microbiol 1997;35:791-5.
de Roda Husman AM, Walboomers JM, Meijer CJ, et al. Analysis of cytomorphologically abnormal cervical scrapes for the presence of 27 mucosotropic human papillomavirus genotypes, using polymerase chain reaction. Int J Cancer 1994;56:802-6.
van den Brule AJ, Pol R, Fransen-Daalmeijer N, et al. GP5+/6+ PCR followed by reverse line blot analysis enables rapid and high-throughput identification of human papillomavirus genotypes. J Clin Microbiol 2002;40:779-87.
Bleeker MC, Hogewoning CJ, Berkhof J, et al. Concordance of specific human papillomavirus types in sex partners is more prevalent than would be expected by chance and is associated with increased viral loads. Clin Infect Dis 2005;41:612-20.
Snijders PJ, van den Brule AJ, Jacobs MV, et al. HPV DNA detection and typing in cervical scrapes. Methods Mol Med 2005;119:101-14.
Davey E, Barratt A, Irwig L, et al. Effect of study design and quality on unsatisfactory rates, cytology classifications, and accuracy in liquid-based versus conventional cervical cytology: a systematic review. Lancet 2006;367:122-32.
Kotaniemi-Talonen L, Nieminen P, Anttila A, et al. Routine cervical screening with primary HPV testing and cytology triage protocol in a randomised setting. Br J Cancer 2005;93:862-7.
Elfgren K, Rylander E, Radberg T, et al. Colposcopic and histopathologic evaluation of women participating in population-based screening for human papillomavirus deoxyribonucleic acid persistence. Am J Obstet Gynecol 2005;193:650-7.
Herrero R, Hildesheim A, Bratti C, et al. Population-based study of human papillomavirus infection and cervical neoplasia in rural Costa Rica. J Natl Cancer Inst 2000;92:464-74.
Arbyn M, Schenck U, Ellison E, et al. Metaanalysis of the accuracy of rapid prescreening relative to full screening of pap smears. Cancer 2003;99:9-16.
Rozendaal L, Walboomers JM, van der Linden JC, et al. PCR-based high-risk HPV test in cervical cancer screening gives objective risk assessment of women with cytomorphologically normal cervical smears. Int J Cancer 1996;68:766-9.
Dalstein V, Riethmuller D, Pretet JL, et al. Persistence and load of high-risk HPV are predictors for development of high-grade cervical lesions: a longitudinal French cohort study. Int J Cancer 2003;106:396-403.
Bulkmans NW, Bleeker MC, Berkhof J, et al. 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 Cancer 2005;117:177-81.
Similar publications
Sorry the service is unavailable at the moment. Please try again later.
This website uses cookies to improve user experience. Read more
Save & Close
Accept all
Decline all
Show detailsHide details
Cookie declaration
About cookies
Strictly necessary
Performance
Strictly necessary cookies allow core website functionality such as user login and account management. The website cannot be used properly without strictly necessary cookies.
This cookie is used by Cookie-Script.com service to remember visitor cookie consent preferences. It is necessary for Cookie-Script.com cookie banner to work properly.
Performance cookies are used to see how visitors use the website, eg. analytics cookies. Those cookies cannot be used to directly identify a certain visitor.
Used to store the attribution information, the referrer initially used to visit the website
Cookies are small text files that are placed on your computer by websites that you visit. Websites use cookies to help users navigate efficiently and perform certain functions. Cookies that are required for the website to operate properly are allowed to be set without your permission. All other cookies need to be approved before they can be set in the browser.
You can change your consent to cookie usage at any time on our Privacy Policy page.