Introduction: In this study, we evaluate the distribution of 24 human papillomavirus (HPV) genotypes in a cohort of 3,381 cytologically screened women from a rural area of northwest Germany, in correlation to cytological diagnoses and histological outcomes. Materials and Methods: We present a retrospective study in which the HPV-genotyping results of women who attended the German cervical screening program were correlated to cytological diagnosis and histological outcome. Results: HPV genotyping showed marked differences among cervical lesions. Although HPV-51 was common in all cervical lesions, it was rarely detected as single-type HPV infection in high-grade cervical intraepithelial neoplasia (CIN)3 (2/118 cases). HPV-16 and 18 were more common in CIN3 (57.6%) than in CIN2 (21.8%), but they were absent in 42.4% of all CIN3 lesions in our cohort. Discussion: Our data show that HPV-16, HPV-31, HPV-51, HPV-53 and HPV-42 are the most prevalent HPV types in the different cervical lesions in this region of northwest Germany.HPV genotyping has been shown to be a powerful tool to triage atypical squamous cells of undetermined significance lesions. Considering the observed heterogeneity of HPV types in CIN2, it could also be useful to triage CIN2+ lesions. Our results underline the usefulness of a morphologically controlled screening program with HPV genotyping as a powerful additional tool.

1.
Bosch FX, Lorincz A, Muñoz N, Meijer CJ, Shah KV: The causal relation between human papillomavirus and cervical cancer. J Clin Pathol 2002;55:244-265.
[PubMed]
2.
Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV, Snijders PJ, Peto J, Meijer CJ, Muñoz N: Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol 1999;189:12-19.
[PubMed]
3.
Schiffman M, Herrero R, Desalle R, Hildesheim A, Wacholder S, Rodriguez AC, Bratti MC, Sherman ME, Morales J, Guillen D, Alfaro M, Hutchinson M, Wright TC, Solomon D, Chen Z, Schussler J, Castle PE, Burk RD: The carcinogenicity of human papillomavirus types reflects viral evolution. Virology 2005;337:76-84.
[PubMed]
4.
de Sanjose S, Quint WG, Alemany L: Human papillomavirus genotype attribution in invasive cervical cancer: a retrospective cross-sectional worldwide study. Lancet Oncol 2010;11:1048-1056.
[PubMed]
5.
Cuzick J, Clavel C, Petry KU, Meijer CJ, Hoyer H, Ratnam S, Szarewski A, Birembaut P, Kulasingam S, Sasieni P, Iftner T: Overview of the European and North American studies on HPV testing in primary cervical cancer screening. Int J Cancer 2006;119:1095-1101.
[PubMed]
6.
de Kok IM, van Rosmalen J, Dillner J, Arbyn M, Sasieni P, Iftner T, van Ballegoojen M: Primary screening for human papillomavirus compared with cytology screening for cervical cancer in European settings: cost effectiveness analysis based on a Dutch microsimulation model. BMJ 2012;344:e670.
[PubMed]
7.
Kijkaart DC, Berkhof J, van Kemenade FJ, Coupe VM, Rozendaal, Heideman DA, Verheijen RH, Bulk S, Verweig W, Snijders PJ, Meijer CJ: HPV DNA testing in population-based cervical screening (VUSA-Screen study): results and implications. Br J Cancer 2012;106:975-981.
[PubMed]
8.
Farnsworth A: Screening for the prevention of cervical cancer in the era of human papillomavirus vaccination: an Australian perspective. Acta Cytol 2011;55:307-312.
[PubMed]
9.
Arbyn M, Anttila A, Jordan J, Schenck U, Ronco G, Segnan N, Wiener H, Herbert A, Daniel J, von Karsa L: European Commission. European Guidelines for Quality Assurance in Cervical Cancer Screening. Second edition - summary document. Ann Oncol 2010;21:448-455.
[PubMed]
10.
de Sanjosé S, Diaz M, Castellsagué X, Clifford G, Bruni L, Muñoz N, Bosch FX: Worldwide prevalence and genotype distribution of cervical human papillomavirus DNA in women with normal cytology, a meta-analysis. Lancet Infect Dis 2007;7:453-459.
[PubMed]
11.
Garcia-García JA, Pérez-Vallés A, Martorell M, Gómez B, Gómez-Cabrero D, Soler F, Calabuig C: Distribution of human papillomavirus types in women from Valencia, Spain, with abnormal cytology. Acta Cytol 2010;54:159-164.
[PubMed]
12.
Klug SJ, Hukelmann M, Hollwitz B, Düzenli N, Schopp B, Petry KU, Iftner T: Prevalence of human papillomavirus types in women screened by cytology in Germany. J Med Virol 2007;79:616-625.
[PubMed]
13.
Agarossi A, Ferrazzi E, Parazzini F, Perno CF, Ghisoni L: Prevalence and type distribution of high-risk human papillomavirus infection in women undergoing voluntary cervical cancer screening in Italy. J Med Virol 2009;81:529-535.
[PubMed]
14.
Evans MF, Adamson CS, Papillo JL, St John TL, Leiman G, Cooper K: Distribution of human papillomavirus types in ThinPrep Papanicolaou tests classified according to the Bethesda 2001 terminology and correlations with patient age and biopsy outcomes. Cancer 2006;106:1054-1064.
[PubMed]
15.
Forslund O, Antonsson A, Edlund K, van den Brule AJ, Hansson BG, Meijer CJ, Ryd W, Rylander E, Strand A, Wadell G, Dillner J, Johansson B: Population-based type-specific prevalence of high-risk human papillomavirus infection in middle-aged Swedish women. J Med Virol 2002;66:535-541.
[PubMed]
16.
Schenck U, von Karsa L: Cervical cancer screening in Germany. Eur J Cancer 2000;36:2221-2226.
[PubMed]
17.
Stanley M, Lowy DR, Frazer I: Chapter 12, Prophylactic HPV vaccines, underlying mechanisms. Vaccine 2006;24:106-113.
[PubMed]
18.
Einstein MH, Baron M, Levin MJ, Chatterjee A, Fox B, Scholar S, Rosen J, Chakhtoura N, Meric D, Dessy FJ, Datta SK, Descamps D, Dubin G, HPV-010 Study Group: Comparative immunogenicity and safety of human papillomavirus (HPV)-16/18 vaccine and HPV-6/11/16/18 vaccine: follow-up from months 12-24 in a phase III randomized study of healthy women aged 18-45 years. Hum Vaccin 2011;7:1343-1358.
[PubMed]
19.
Solomon D, Davey D, Kurman R, Moriarty A, O'Connor D, Prey M, Raab S, Sherman M, Wilbur D, Wright T, Young N; Forum Group Members, Bethesda 2001 Workshop: The 2001 Bethesda System, terminology for reporting results of cervical cytology. JAMA 2002;287:2114-2119.
[PubMed]
20.
Dijkstra MG, Heideman DA, de Roy SC, Rozendaal L, Berkhof J, van Krimpen K, van Groningen K, Snijders PJ, Meijer CJ, van Kemenade FJ: p16(INK4a) immunostaining as an alternative to histology review for reliable grading of cervical intraepithelial lesions. J Clin Pathol 2010;63:972-977.
[PubMed]
21.
Gustinucci D, Passamonti B, Cesarini E, Butera D, Palmieri EA, Bulletti S, Carlani A, Staiano M, D'Amico MR, D'Angelo V, Di Dato E, Martinelli N, Malaspina M, Spita N, Tintori B, Fulciniti F: Role of p16(INK4a) cytology testing as an adjunct to enhance the diagnostic specificity and accuracy in human papillomavirus-positive women within an organized cervical cancer screening program. Acta Cytol 2012;56:506-514.
[PubMed]
22.
Hesselink AT, Heideman DA, Berkhof J, Topal F, Pol RP, Meijer CJ, Snijders PJ: Comparison of the clinical performance of PapilloCheck human papillomavirus detection with that of the GP5+/6+-PCR-enzyme immunoassay in population-based cervical screening. J Clin Microbiol 2010;48:797-801.
[PubMed]
23.
Schopp B, Holz B, Zago M, Stubenrauch F, Petry KU, Kjaer SK, Iftner T: Evaluation of the performance of the novel PapilloCheck HPV genotyping test by comparison with two other genotyping systems and the HC2 test. J Med Virol 2010;82:605-615.
[PubMed]
24.
WHO/ICO Information Centre on HPV and Cervical Cancer (HPV Information Centre): Human papillomavirus and related cancers in Germany. Summary report 2010. www.who.int/hpvcentre (accessed April 12, 2013).
25.
Kovács K, Varnai AD, Bollmann M, Bankfalvi A, Szendy M, Speich N, Schmitt C, Pajor L, Bollmann R: Prevalence and genotype distribution of multiple human papillomavirus infection in the uterine cervix: a 7.5-year longitudinal study in a routine cytology-based screening population in West Germany. J Med Virol 2008;80:1814-1823.
[PubMed]
26.
Snijders PJ, van den Brule AJ, Meijer CJ: The clinical relevance of human papillomavirus testing, relationship between analytical and clinical sensitivity. J Pathol 2003;201:1-6.
[PubMed]
27.
Klug SJ, Molijn A, Schopp B, Holz B, Iftner A, Quint W,JF Snijders P, Petry KU, Krüger Kjaer S, Munk C, Iftner T: Comparison of the performance of different HPV genotyping methods for detecting genital HPV types. J Med Virol 2008;80:1264-1274.
[PubMed]
28.
Bandyopadhyay S, Austin RM, Dabbs D, Zhao C: Adjunctive human papillomavirus DNA testing is a useful option in some clinical settings for disease risk assessment and triage of females with ASC-H Papanicolaou test results. Arch Pathol Lab Med 2008;132:1874-1881.
[PubMed]
29.
Davey DD, Greenspan DL, Kurtycz DF, Husain M, Austin RM: 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 2010;14:206-214.
[PubMed]
30.
Washiya K, Takamizu R, Kumagai Y, Himeji Y, Kobayashi T, Iwai M, Watanabe J: Worldwide web-based cytological analysis of atypical squamous cells cannot exclude high-grade intraepithelial lesions. Acta Cytol 2012;56:47-54.
[PubMed]
31.
Stoler MH, Schiffman M, Atypical Squamous Cells of Undetermined Significance-Low-grade Squamous Intraepithelial Lesion Triage Study (ALTS) Group: Interobserver reproducibility of cervical cytologic and histologic interpretations, realistic estimates from the ASCUS-LSIL Triage Study. JAMA 2001;285:1500-1505.
[PubMed]
32.
Smith JS, Melendy A, Rana RK, Pimenta JM: Age-specific prevalence of infection with human papillomavirus in females, a global review. J Adolesc Health 2008;43:5-25.
[PubMed]
33.
The Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesions Triage Study (ALTS) Group: Human papillomavirus testing for triage of women with cytologic evidence of low-grade squamous intraepithelial lesions, baseline data from a randomized trial. J Natl Cancer Inst 2000;92:397-402.
[PubMed]
34.
Iftner T, Eberle S, Iftner A, Holz B, Banik N, Quint W, Straube AN: Prevalence of low-risk and high-risk types of human papillomavirus and other risk factors for HPV infection in Germany within different age groups in women up to 30 years of age, an epidemiological observational study. J Med Virol 2010;82:1928-1939.
[PubMed]
35.
Bollmann R, Bankfalvi A, Griefingholt H, Trosic A, Speich N, Schmitt C, Bollmann M: Validity of combined cytology and human papillomavirus (HPV) genotyping with adjuvant DNA-cytometry in routine cervical screening, results from 31,031 women from the Bonn region in West Germany. Oncol Rep 2005;13:915-922.
[PubMed]
36.
Clifford GM, Rana RK, Franceschi S, Smith JS, Gough G, Pimenta JM: Human papillomavirus genotype distribution in low-grade cervical lesions, comparison by geographic region and with cervical cancer. Cancer Epidemiol Biomarkers Prev 2005;14:1157-1164.
[PubMed]
37.
Smith JS, Lindsay L, Hoots B, Keys J, Franceschi S, Winer R, Clifford GM: Human papillomavirus type distribution in invasive cervical cancer and high-grade cervical lesions, a meta-analysis update. Int J Cancer 2007;121:621-632.
[PubMed]
38.
Bosch FX, Burchell AN, Schiffman M, Giuliano AR, de Sanjose S, Bruni L, Tortolero-Luna G, Kjaer SK, Muñoz N: Epidemiology and natural history of human papillomavirus infections and type-specific implications in cervical neoplasia. Vaccine 2008;26(suppl 10):K1-K16.
[PubMed]
39.
Ostör AG: Natural history of cervical intraepithelial neoplasia, a critical review. Int J Gynecol Pathol 1993;12:186-192.
[PubMed]
40.
Brown DR, Kjaer SK, Sigurdsson K, Iversen OE, Hernandez-Avila M, Wheeler CM, Perez G, Koutsky LA, Tay EH, Garcia P, Ault KA, Garland SM, Leodolter S, Olsson SE, Tang GW, Ferris DG, Paavonen J, Steben M, Bosch FX, Dillner J, Joura EA, Kurman RJ, Majewski S, Muñoz N, Myers ER, Villa LL, Taddeo FJ, Roberts C, Tadesse A, Bryan J, Lupinacci LC, Giacoletti KE, Sings HL, James M, Hesley TM, Barr E: The impact of quadrivalent human papillomavirus (HPV; types 6, 11, 16, and 18) L1 virus-like particle vaccine on infection and disease due to oncogenic nonvaccine HPV types in generally HPV-naive women aged 16-26 years. J Infect Dis 2009;199:926-935.
[PubMed]
41.
Philipp W, Honoré N, Sapp M, Cole ST, Streeck RE: Human papillomavirus type 42, new sequences, conserved genome organization. Virology 1992;186:331-334.
[PubMed]
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