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Published in: BMC Cancer 1/2013

Open Access 01-12-2013 | Research article

Annual Papanicolaou screening for 5 years among human papillomavirus-negative women

Authors: Karl Ulrich Petry, Franziska Rinnau, Gerd Böhmer, Bettina Hollwitz, Alexander Luyten, Nina Buttmann, Martin Brünger, Thomas Iftner

Published in: BMC Cancer | Issue 1/2013

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Abstract

Background

Primary human papilloma virus (HPV) screening is more effective than cytology in reducing the risk of cervical cancer, but screening intervals should be extended in HPV-negative women. However, some Markov models predicted that long intervals are associated with an excess risk of cervical cancer. The aim of this analysis was to estimate the real-life risks and benefits of annual Papanicolaou (Pap) screening in HPV-negative women with normal cytology.

Methods

Women with negative Hybrid Capture 2 (HC2) results and normal cytology at the time of inclusion in the Hannover HPV screening trial underwent annual Pap smears for 5 years. A subgroup was randomly selected for retesting with cytology, HC2, and colposcopy 60–68 months after recruitment.

Results

Of 4236 women included, 3406 had at least one Pap smear, but only 1185 attended all five annual screening visits. The proportion of women with at least one abnormal smear was 14.4% in 60 months. The probability of abnormal smears increased continuously over time. No case of ≥ CIN2+ was observed during 5 years. Of 605 women selected for subgroup analysis, 292 agreed to be retested (48.3%). The rate of high-risk HPV at 60–68 months was 3.0% (9/296).

Conclusions

The long-term risk of high-grade neoplasia after an initial negative HC2 test and normal cytology result was low, while the rate of false-positive abnormal Pap smears was significant and increased constantly over time. Pap smear screening of HPV-negative women more frequently than every 5 years could be potentially harmful and seems to be of little clinical value.
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Literature
1.
go back to reference Rijkaart DC, Berkhof J, Rozendaal L, van Kemenade FJ, Bulkmans NW, Heideman DA, Kenter GG, Cuzick J, Snijders PJ, Meijer CJ: Human papillomavirus testing for the detection of high-grade cervical intraepithelial neoplasia and cancer: final results of the POBASCAM randomised controlled trial. Lancet Oncol. 2012, 13: 78-88. 10.1016/S1470-2045(11)70296-0.CrossRefPubMed Rijkaart DC, Berkhof J, Rozendaal L, van Kemenade FJ, Bulkmans NW, Heideman DA, Kenter GG, Cuzick J, Snijders PJ, Meijer CJ: Human papillomavirus testing for the detection of high-grade cervical intraepithelial neoplasia and cancer: final results of the POBASCAM randomised controlled trial. Lancet Oncol. 2012, 13: 78-88. 10.1016/S1470-2045(11)70296-0.CrossRefPubMed
2.
go back to reference Arbyn M, Ronco G, Anttila A, Meijer CJ, Poljak M, Ogilvie G, Koliopoulos G, Naucler P, Sankaranarayanan R, Peto J: Evidence regarding human papillomavirus testing in secondary prevention of cervical cancer. Vaccine. 2012, 30 (Suppl 5): F88-F99.CrossRefPubMed Arbyn M, Ronco G, Anttila A, Meijer CJ, Poljak M, Ogilvie G, Koliopoulos G, Naucler P, Sankaranarayanan R, Peto J: Evidence regarding human papillomavirus testing in secondary prevention of cervical cancer. Vaccine. 2012, 30 (Suppl 5): F88-F99.CrossRefPubMed
3.
go back to reference Arbyn M, Anttila A, Jordan J, Ronco G, Schenck U, Segnan N, Wiener H, Herbert A, von Karsa L: European guidelines for quality assurance in cervical cancer screening. Second edition – summary document. Ann Oncol. 2010, 21: 448-458. 10.1093/annonc/mdp471.CrossRefPubMedPubMedCentral Arbyn M, Anttila A, Jordan J, Ronco G, Schenck U, Segnan N, Wiener H, Herbert A, von Karsa L: European guidelines for quality assurance in cervical cancer screening. Second edition – summary document. Ann Oncol. 2010, 21: 448-458. 10.1093/annonc/mdp471.CrossRefPubMedPubMedCentral
4.
go back to reference Sawaya GF, McConnell KJ, Kulasingam SL, Lawson HW, Kerlikowske K, Melnikow J, Lee NC, Gildengorin G, Myers ER, Washington AE: Risk of cervical cancer associated with extending the interval between cervical-cancer screenings. N Engl J Med. 2003, 349: 1501-1509. 10.1056/NEJMoa035419.CrossRefPubMed Sawaya GF, McConnell KJ, Kulasingam SL, Lawson HW, Kerlikowske K, Melnikow J, Lee NC, Gildengorin G, Myers ER, Washington AE: Risk of cervical cancer associated with extending the interval between cervical-cancer screenings. N Engl J Med. 2003, 349: 1501-1509. 10.1056/NEJMoa035419.CrossRefPubMed
5.
go back to reference Sroczynski G, Schnell-Inderst P, Mühlberger N, Lang K, Aidelsburger P, Wasem J, Mittendorf T, Engel J, Hillemanns P, Petry KU, Krämer A, Siebert U: Cost-effectiveness of primary HPV screening for cervical cancer in Germany – a decision analysis. Eur J Cancer. 2011, 47: 1633-1646. 10.1016/j.ejca.2011.03.006.CrossRefPubMed Sroczynski G, Schnell-Inderst P, Mühlberger N, Lang K, Aidelsburger P, Wasem J, Mittendorf T, Engel J, Hillemanns P, Petry KU, Krämer A, Siebert U: Cost-effectiveness of primary HPV screening for cervical cancer in Germany – a decision analysis. Eur J Cancer. 2011, 47: 1633-1646. 10.1016/j.ejca.2011.03.006.CrossRefPubMed
6.
go back to reference Petry KU, Menton S, Menton M, van Loenen-Frosch F, de Carvalho Gomes H, Holz B, Schopp B, Garbrecht-Buettner S, Davies P, Boehmer G, van den Akker E, Iftner T: Inclusion of HPV testing in routine cervical cancer screening for women above 29 years in Germany: results for 8466 patients. Br J Cancer. 2003, 88: 1570-1577. 10.1038/sj.bjc.6600918.CrossRefPubMedPubMedCentral Petry KU, Menton S, Menton M, van Loenen-Frosch F, de Carvalho Gomes H, Holz B, Schopp B, Garbrecht-Buettner S, Davies P, Boehmer G, van den Akker E, Iftner T: Inclusion of HPV testing in routine cervical cancer screening for women above 29 years in Germany: results for 8466 patients. Br J Cancer. 2003, 88: 1570-1577. 10.1038/sj.bjc.6600918.CrossRefPubMedPubMedCentral
7.
go back to reference Dillner J, Rebolj M, Birembaut P, Petry KU, Szarewski A, Munk C, de Sanjose S, Naucler P, Lloveras B, Kjaer S, Cuzick J, van Ballegooijen M, Clavel C, Iftner T: Joint European Cohort Study: Long term predictive values of cytology and human papillomavirus testing in cervical cancer screening: joint European cohort study. BMJ. 2008, 337: a1754-10.1136/bmj.a1754.CrossRefPubMedPubMedCentral Dillner J, Rebolj M, Birembaut P, Petry KU, Szarewski A, Munk C, de Sanjose S, Naucler P, Lloveras B, Kjaer S, Cuzick J, van Ballegooijen M, Clavel C, Iftner T: Joint European Cohort Study: Long term predictive values of cytology and human papillomavirus testing in cervical cancer screening: joint European cohort study. BMJ. 2008, 337: a1754-10.1136/bmj.a1754.CrossRefPubMedPubMedCentral
8.
go back to reference Deutsche Gesellschaft für Gynäkologie und Geburtshilfe (DGGG): Leitlinie: Prävention, Diagnostik und Therapie der HPV-Infektion und präinvasiver Läsionen des weiblichen Genitale. 2008, Berlin: Verlag S. Kramarz Deutsche Gesellschaft für Gynäkologie und Geburtshilfe (DGGG): Leitlinie: Prävention, Diagnostik und Therapie der HPV-Infektion und präinvasiver Läsionen des weiblichen Genitale. 2008, Berlin: Verlag S. Kramarz
9.
go back to reference Petry KU, Luyten A, Scherbring S: Accuracy of colposcopy management to detect CIN3 and invasive cancer in women with abnormal screening tests: Results from a primary HPV screening project from 2006 to 2011 in Wolfsburg, Germany. Gynecol Oncol. 2013, 128: 282-287. 10.1016/j.ygyno.2012.10.017.CrossRefPubMed Petry KU, Luyten A, Scherbring S: Accuracy of colposcopy management to detect CIN3 and invasive cancer in women with abnormal screening tests: Results from a primary HPV screening project from 2006 to 2011 in Wolfsburg, Germany. Gynecol Oncol. 2013, 128: 282-287. 10.1016/j.ygyno.2012.10.017.CrossRefPubMed
10.
go back to reference Kaplan EL, Meier P: Nonparametric estimation from incomplete observation. J Am Stat Assoc. 1958, 53: 457-481. 10.1080/01621459.1958.10501452.CrossRef Kaplan EL, Meier P: Nonparametric estimation from incomplete observation. J Am Stat Assoc. 1958, 53: 457-481. 10.1080/01621459.1958.10501452.CrossRef
11.
go back to reference Cox RD: Regression models and life-tables. J R Stat Soc Series B Stat Methodol. 1972, 34: 187-220. Cox RD: Regression models and life-tables. J R Stat Soc Series B Stat Methodol. 1972, 34: 187-220.
12.
go back to reference Petry KU, Breugelmans JG, Benard S, Lamure E, Littlewood KJ, Hillemanns P: Cost of screening and treatment of cervical dyskaryosis in Germany. Eur J Gynaecol Oncol. 2008, 29: 345-349.PubMed Petry KU, Breugelmans JG, Benard S, Lamure E, Littlewood KJ, Hillemanns P: Cost of screening and treatment of cervical dyskaryosis in Germany. Eur J Gynaecol Oncol. 2008, 29: 345-349.PubMed
13.
go back to reference Sawaya GF: Rightsizing cervical cancer screening. Arch Intern Med. 2010, 170: 985-986. 10.1001/archinternmed.2010.133.CrossRefPubMed Sawaya GF: Rightsizing cervical cancer screening. Arch Intern Med. 2010, 170: 985-986. 10.1001/archinternmed.2010.133.CrossRefPubMed
14.
go back to reference 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: 489-498. 10.1016/S0140-6736(06)68181-6.CrossRefPubMed 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: 489-498. 10.1016/S0140-6736(06)68181-6.CrossRefPubMed
15.
go back to reference Arbyn M, Kyrgiou M, Simoens C, Raifu AO, Koliopoulos G, Martin-Hirsch P, Prendiville W, Paraskevaidis E: Perinatal mortality and other severe adverse pregnancy outcomes associated with treatment of cervical intraepithelial neoplasia: meta-analysis. BMJ. 2008, 337: a1284-10.1136/bmj.a1284.CrossRefPubMedPubMedCentral Arbyn M, Kyrgiou M, Simoens C, Raifu AO, Koliopoulos G, Martin-Hirsch P, Prendiville W, Paraskevaidis E: Perinatal mortality and other severe adverse pregnancy outcomes associated with treatment of cervical intraepithelial neoplasia: meta-analysis. BMJ. 2008, 337: a1284-10.1136/bmj.a1284.CrossRefPubMedPubMedCentral
16.
go back to reference Roland KB, Soman A, Benard VB, Saraiya M: Human papillomavirus and Papanicolaou tests screening interval recommendations in the United States. Am J Obstet Gynecol. 2011, 205 (447): e1-8.PubMed Roland KB, Soman A, Benard VB, Saraiya M: Human papillomavirus and Papanicolaou tests screening interval recommendations in the United States. Am J Obstet Gynecol. 2011, 205 (447): e1-8.PubMed
17.
go back to reference Moyer VA: U.S. Preventive Services Task Force: Screening for cervical cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2012, 156: 880-891. 10.7326/0003-4819-156-12-201206190-00424. W312CrossRefPubMed Moyer VA: U.S. Preventive Services Task Force: Screening for cervical cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2012, 156: 880-891. 10.7326/0003-4819-156-12-201206190-00424. W312CrossRefPubMed
18.
go back to reference Jin XW, Sikon A, Yen-Lieberman B: Cervical cancer screening: less testing, smarter testing. Cleve Clin J Med. 2011, 78: 737-747. 10.3949/ccjm.78a.11033.CrossRefPubMed Jin XW, Sikon A, Yen-Lieberman B: Cervical cancer screening: less testing, smarter testing. Cleve Clin J Med. 2011, 78: 737-747. 10.3949/ccjm.78a.11033.CrossRefPubMed
19.
go back to reference Saraiya M, Berkowitz Z, Yabroff KR, Wideroff L, Kobrin S, Benard V: Cervical cancer screening with both human papillomavirus and Papanicolaou testing vs Papanicolaou testing alone: what screening intervals are physicians recommending?. Arch Intern Med. 2010, 170: 977-985. 10.1001/archinternmed.2010.134.CrossRefPubMed Saraiya M, Berkowitz Z, Yabroff KR, Wideroff L, Kobrin S, Benard V: Cervical cancer screening with both human papillomavirus and Papanicolaou testing vs Papanicolaou testing alone: what screening intervals are physicians recommending?. Arch Intern Med. 2010, 170: 977-985. 10.1001/archinternmed.2010.134.CrossRefPubMed
Metadata
Title
Annual Papanicolaou screening for 5 years among human papillomavirus-negative women
Authors
Karl Ulrich Petry
Franziska Rinnau
Gerd Böhmer
Bettina Hollwitz
Alexander Luyten
Nina Buttmann
Martin Brünger
Thomas Iftner
Publication date
01-12-2013
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2013
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-13-379

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