Consistent condom use increases spontaneous regression in high-risk non-HPV16 but not in HPV16 CIN2-3 lesions, a prospective population-based cohort study

Infectious Agents and Cancer

Jan PA Baak³  Emiel AM Janssen³  Ivar Skaland³  Arnold-Jan Kruse²  Bianca van Diermen-Hidle³  Bent Fiane¹  Kjell Løvslett¹  Einar Gudlaugsson³  Irene Tveiterås Øvestad³  Ane Cecilie Munk¹ 

[1] Department of Obstetrics and Gynecology, Stavanger University Hospital, Stavanger, Norway;Department of Gynecology, Academic Hospital Maastricht, Maastricht, The Netherlands;Department of Pathology, Stavanger University Hospital, Box 8100, 4068, Stavanger, Norway

关键词: Clinical factors;    Condom use;    Regression;    HPV16;    High-risk HPV;    CIN2-3;   

Others  :  803350
DOI  :  10.1186/1750-9378-7-30

 received in 2012-08-30, accepted in 2012-10-31,  发布年份 2012

【 摘 要 】

Background

The major cause of cervical intraepithelial neoplasia (CIN) is persistent infection with human papillomavirus (HPV). Most CIN grade 2 and 3 lesions are treated with cone excision, although a substantial proportion (6-50%) of CIN2-3 lesions will regresses spontaneously. Predictors for regression of CIN2-3 are desirable in order to reduce this overtreatment.

Methods

In this prospective cohort study, 145 consecutive women with first-time onset CIN2-3 in colposcopy-directed biopsies and standardized biopsy-cone excision interval were included. The genotype of the high-risk human papillomaviruses (=hrHPV) and clinical factors including sexual behaviour, parity, contraception and smoking were assessed. Patients were divided into two groups according to lesions containing HPV16 (hrHPV16+) and high-risk non-HPV16 (hrHPV16-) genotypes.

Results

Women whose partners consistently used condoms showed a significantly higher regression rate than women using other types of contraception (53% versus 13%, p<0.0001). However, this effect was only seen in hrHPV16- patients (73% regression rate versus 13%, p<0.0001). HrHPV16+ patients had a significantly higher number of sexual partners and more current smokers compared to hrHPV16- patients. The regression rate was not significantly different in CIN2-3 lesions containing HPV16 (hrHPV16+) versus hrHPV16- genotypes.

Conclusions

Heterogeneity among hrHPV genotypes excists. HPV-genotype analyses can identify women who significantly increase their chance of regression by consistent condom use.

【 授权许可】

   
2012 Munk et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

【 参考文献 】

• [1]Coutlee F, Ratnam S, Ramanakumar AV, Insinga RR, Bentley J, Escott N, Ghatage P, Koushik A, Ferenczy A, Franco EL: Distribution of human papillomavirus genotypes in cervical intraepithelial neoplasia and invasive cervical cancer in Canada. J Med Virol 2011, 83(6):1034-1041.
• [2]Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV, Snijders PJ, Peto J, Meijer CJ, Munoz N: Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol 1999, 189(1):12-19.
• [3]Bosch FX, de Sanjose S: Chapter 1: Human papillomavirus and cervical cancer–burden and assessment of causality. J Natl Cancer Inst Monogr 2003, 31:3-13.
• [4]Aral SO, Adimora AA, Fenton KA: Understanding and responding to disparities in HIV and other sexually transmitted infections in African Americans. Lancet 2008, 372(9635):337-340.
• [5]Syrjanen K, Hakama M, Saarikoski S, Vayrynen M, Yliskoski M, Syrjanen S, Kataja V, Castren O: Prevalence, incidence, and estimated life-time risk of cervical human papillomavirus infections in a nonselected Finnish female population. Sex Transm Dis 1990, 17(1):15-19.
• [6]Ho GY, Bierman R, Beardsley L, Chang CJ, Burk RD: Natural history of cervicovaginal papillomavirus infection in young women. N Engl J Med 1998, 338(7):423-428.
• [7]Woodman CB, Collins S, Winter H, Bailey A, Ellis J, Prior P, Yates M, Rollason TP, Young LS: Natural history of cervical human papillomavirus infection in young women: a longitudinal cohort study. Lancet 2001, 357(9271):1831-1836.
• [8]Koutsky LA, Holmes KK, Critchlow CW, Stevens CE, Paavonen J, Beckmann AM, DeRouen TA, Galloway DA, Vernon D, Kiviat NB: A cohort study of the risk of cervical intraepithelial neoplasia grade 2 or 3 in relation to papillomavirus infection. N Engl J Med 1992, 327(18):1272-1278.
• [9]Rozendaal L, Westerga J, van der Linden JC, Walboomers JM, Voorhorst FJ, Risse EK, Boon ME, Meijer CJ: PCR based high risk HPV testing is superior to neural network based screening for predicting incident CIN III in women with normal cytology and borderline changes. J Clin Pathol 2000, 53(8):606-611.
• [10]Ostor AG: Natural history of cervical intraepithelial neoplasia: a critical review. Int J Gynecol Pathol 1993, 12(2):186-192.
• [11]Nasiell K, Nasiell M, Vaclavinkova V: Behavior of moderate cervical dysplasia during long-term follow-up. Obstet Gynecol 1983, 61(5):609-614.
• [12]Baak JP, Kruse AJ, Robboy SJ, Janssen EA, van Diermen B, Skaland I: Dynamic behavioural interpretation of cervical intraepithelial neoplasia with molecular biomarkers. J Clin Pathol 2006, 59(10):1017-1028.
• [13]Ovestad IT, Gudlaugsson E, Skaland I, Malpica A, Kruse AJ, Janssen EA, Baak JP: Local immune response in the microenvironment of CIN2-3 with and without spontaneous regression. Modern pathology: an official journal of the United States and Canadian Academy of Pathology, Inc 2010, 23(9):1231-1240.
• [14]International Collaboration of Epidemiological Studies of Cervical Cancer: Cervical carcinoma and sexual behavior: collaborative reanalysis of individual data on 15,461 women with cervical carcinoma and 29,164 women without cervical carcinoma from 21 epidemiological studies. Cancer epidemiology, biomarkers & prevention: a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 2009, 18(4):1060-1069.
• [15]Munoz N, Franceschi S, Bosetti C, Moreno V, Herrero R, Smith JS, Shah KV, Meijer CJ, Bosch FX: Role of parity and human papillomavirus in cervical cancer: the IARC multicentric case–control study. Lancet 2002, 359(9312):1093-1101.
• [16]Smith JS, Green J, Berrington de Gonzalez A, Appleby P, Plummer M, Beral V: Cervical cancer and use of hormonal contraceptives: a systematic review. Lancet 2003, 361(9364):1159-1167.
• [17]Trimble CL, Genkinger JM, Burke AE, Hoffman SC, Helzlsouer KJ, Diener-West M, Comstock GW, Alberg AJ: Active and passive cigarette smoking and the risk of cervical neoplasia. Obstet Gynecol 2005, 105(1):174-181.
• [18]Trimble CL, Piantadosi S, Gravitt P, Ronnett B, Pizer E, Elko A, Wilgus B, Yutzy W, Daniel R, Shah K, et al.: Spontaneous regression of high-grade cervical dysplasia: effects of human papillomavirus type and HLA phenotype. Clinical cancer research: an official journal of the American Association for Cancer Research 2005, 11(13):4717-4723.
• [19]Wentzensen N, Walker J, Schiffman M, Yang HP, Zuna RE, Dunn ST, Allen RA, Zhang R, Sherman M, Gold MA, Wang SS: Heterogeneity of high grade cervical intraepithelial neoplasia related to HPV16: Implications for natural history and management. Int J Cancer 2013 Jan 1, 132(1):148-154.
• [20]Baak JP, Kruse AJ, Garland SM, Skaland I, Janssen EA, Tabrizi S, Fagerheim S, Robboy S, Nilsen ST: Combined p53 and retinoblastoma protein detection identifies persistent and regressive cervical high-grade squamous intraepithelial lesions. Am J Surg Pathol 2005, 29(8):1062-1066.
• [21]McCredie MR, Sharples KJ, Paul C, Baranyai J, Medley G, Jones RW, Skegg DC: Natural history of cervical neoplasia and risk of invasive cancer in women with cervical intraepithelial neoplasia 3: a retrospective cohort study. The lancet oncology 2008, 9(5):425-434.
• [22]Hagen B, Skjeldestad FE, Bratt H, Tingulstad S, Lie AK: CO2 laser conization for cervical intraepithelial neoplasia grade II-III: complications and efficacy. Acta Obstet Gynecol Scand 1998, 77(5):558-563.
• [23]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(9509):489-498.
• [24]Albrechtsen S, Rasmussen S, Thoresen S, Irgens LM, Iversen OE: Pregnancy outcome in women before and after cervical conisation: population based cohort study. BMJ 2008, 337:a1343.
• [25]Barken SS, Rebolj M, Andersen ES, Lynge E: Frequency of cervical intraepithelial neoplasia treatment in a well-screened population. Int J Cancer 2012, 130(10):2438-2444.
• [26]Munk AC, Kruse AJ, van Diermen B, Janssen EA, Skaland I, Gudlaugsson E, Nilsen ST, Baak JP: Cervical intraepithelial neoplasia grade 3 lesions can regress. APMIS: acta pathologica, microbiologica, et immunologica Scandinavica 2007, 115(12):1409-1414.
• [27]Munoz N, Bosch FX, de Sanjose S, Herrero R, Castellsague X, Shah KV, Snijders PJ, Meijer CJ: Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med 2003, 348(6):518-527.
• [28]Cogliano V, Baan R, Straif K, Grosse Y, Secretan B, El Ghissassi F: Carcinogenicity of human papillomaviruses. Lancet Oncol 2005, 6(4):204.
• [29]Kjaer SK, Frederiksen K, Munk C, Iftner T: Long-term absolute risk of cervical intraepithelial neoplasia grade 3 or worse following human papillomavirus infection: role of persistence. J Natl Cancer Inst 2010, 102(19):1478-1488.
• [30]Steen R, Johansen BK, Skare G, Haldorsen T, Eriksen T, Waage R, Molund IM: Annual Report Cervical Cancer Screening 2008. Cancer Registry of Norway 2009.
• [31]WHO: IARC Classification of Tumors of the Breast and Female Genital Organs, vol. Book 4. IARCPress, Lyon; 2003.
• [32]Kruse AJ, Baak JP, de Bruin PC, Jiwa M, Snijders WP, Boodt PJ, Fons G, Houben PW, The HS: Ki-67 immunoquantitation in cervical intraepithelial neoplasia (CIN): a sensitive marker for grading. J Pathol 2001, 193(1):48-54.
• [33]Soreide K: Receiver-operating characteristic curve analysis in diagnostic, prognostic and predictive biomarker research. J Clin Pathol 2009, 62(1):1-5.
• [34]Khan MJ, Castle PE, Lorincz AT, Wacholder S, Sherman M, Scott DR, Rush BB, Glass AG, Schiffman M: The elevated 10-year risk of cervical precancer and cancer in women with human papillomavirus (HPV) type 16 or 18 and the possible utility of type-specific HPV testing in clinical practice. J Natl Cancer Inst 2005, 97(14):1072-1079.
• [35]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(3):621-632.
• [36]Li N, Franceschi S, Howell-Jones R, Snijders PJ, Clifford GM: Human papillomavirus type distribution in 30,848 invasive cervical cancers worldwide: Variation by geographical region, histological type and year of publication. Int J Cancer 2011, 128(4):927-935.
• [37]Hogewoning CJ, Bleeker MC, van den Brule AJ, Voorhorst FJ, Snijders PJ, Berkhof J, Westenend PJ, Meijer CJ: Condom use promotes regression of cervical intraepithelial neoplasia and clearance of human papillomavirus: a randomized clinical trial. Int J Cancer 2003, 107(5):811-816.
• [38]Rousseau MC, Franco EL, Villa LL, Sobrinho JP, Termini L, Prado JM, Rohan TE: A cumulative case–control study of risk factor profiles for oncogenic and nononcogenic cervical human papillomavirus infections. Cancer epidemiology, biomarkers & prevention: a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 2000, 9(5):469-476.
• [39]Olsen AO, Dillner J, Skrondal A, Magnus P: Combined effect of smoking and human papillomavirus type 16 infection in cervical carcinogenesis. Epidemiology 1998, 9(3):346-349.
• [40]McCann MF, Irwin DE, Walton LA, Hulka BS, Morton JL, Axelrad CM: Nicotine and cotinine in the cervical mucus of smokers, passive smokers, and nonsmokers. Cancer epidemiology, biomarkers & prevention: a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 1992, 1(2):125-129.
• [41]Poppe WA, Peeters R, Daenens P, Ide PS, Van Assche FA: Tobacco smoking and the uterine cervix: cotinine in blood, urine and cervical fluid. Gynecol Obstet Invest 1995, 39(2):110-114.
• [42]Lam TH, Stewart SM, Ho LM: Smoking and high-risk sexual behavior among young adults in Hong Kong. J Behav Med 2001, 24(5):503-518.
• [43]Kelly RW: Immunosuppressive mechanisms in semen: implications for contraception. Hum Reprod 1995, 10(7):1686-1693.
• [44]Wang X, Zhuang J, Wu K, Xu R, Li M, Lu Y: Human semen: the biological basis of sexual behaviour to promote human papillomavirus infection and cervical cancer. Med Hypotheses 2010, 74(6):1015-1016.
• [45]Ovestad IT, Gudlaugsson E, Skaland I, Malpica A, Munk AC, Janssen EA, Baak JP: The impact of epithelial biomarkers, local immune response and human papillomavirus genotype in the regression of cervical intraepithelial neoplasia grades 2–3. J Clin Pathol 2011, 64(4):303-307.