[en] Recent studies have identified a putative cell of origin for cervical intraepithelial neoplasia (CIN) and cervical cancer at the squamo-columnar junction (SCJ) and suggest that these cells may not regenerate following excision (LEEP). This study addressed the impact of SCJ excision on the temporal dynamics, histologic and viral (HPV) characteristics of recurrent CIN. One hundred thirty one consecutive patients treated by excision and attending follow-up visits were enrolled. We compared recurrent and initial CIN with attention to excision margins, timing of recurrence, CIN grade, HPV types, p16 immunophenotype, and SCJ immunophenotype. During the follow-up period (up to four years), sixteen (12.2%) recurrences were identified. Four (25%) were identified at the first follow-up visit, closely resembled the initial CIN 2/3 in grade and HPV type, and were typically SCJ marker positive [SCJ(+)], suggesting non-excised (residual) disease. Twelve (75%) manifested after the first postoperative visit and all were in the ectocervix or in mature metaplastic epithelium. All of the 12 delayed recurrences were classified as CIN 1 and were SCJ (-). Nine of 11 SCJ (-) recurrences (82%) followed regressed spontaneously. Taken together, these results show that new lesions developing from any HPV infection are delayed and occur within the ectocervix or metaplastic epithelium. This dramatically lower risk of CIN 2/3 following successful SCJ excision suggests that removal of the SCJ could be a critical variable in reducing the risk of subsequent CIN 2/3 and cervical cancer. (c) 2014 Wiley Periodicals, Inc.
Disciplines :
Oncology
Author, co-author :
Herfs, Michael ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques
SOMJA, Joan ; Centre Hospitalier Universitaire de Liège - CHU > Anatomie pathologique
Howitt, Brooke E.
Suarez-Carmona, Meggy ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques
KUSTERMANS, Gaëlle ; Centre Hospitalier Universitaire de Liège - CHU > Anatomie pathologique
Hubert, Pascale ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques
DOYEN, Jean ; Centre Hospitalier Universitaire de Liège - CHU > Gynécologie-Obstétrique
GOFFIN, Frédéric ; Centre Hospitalier Universitaire de Liège - CHU > Gynécologie-Obstétrique CHR
Kridelka, Frédéric ; Université de Liège - ULiège > Département des sciences cliniques > Gynécologie-Obstétrique
Crum, Christopher P.
Delvenne, Philippe ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques
Language :
English
Title :
Unique recurrence patterns of cervical intraepithelial neoplasia following excision of the squamo-columnar junction.
Publication date :
2015
Journal title :
International Journal of Cancer
ISSN :
0020-7136
eISSN :
1097-0215
Publisher :
John Wiley & Sons, Hoboken, United States - New York
Crum CP, Ikenberg H, Richart RM, et al. Human papillomavirus type 16 and early cervical neoplasia. N Engl J Med 1984;310:880-3.
Durst M, Gissmann L, Ikenberg H, et al. A papillomavirus DNA from a cervical carcinoma and its prevalence in cancer biopsy samples from different geographic regions. Proc Natl Acad Sci USA 1983;80:3812-5.
Lehtinen M, Paavonen J, Wheeler CM, et al. Overall efficacy of HPV-16/18 AS04-adjuvanted vaccine against grade 3 or greater cervical intraepithelial neoplasia: 4-year end-of-study analysis of the randomised, double-blind PATRICIA trial. Lancet Oncol 2012;13:89-99.
Paavonen J, Naud P, Salmeron J, et al. Efficacy of human papillomavirus (HPV) 216/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by oncogenic HPV types (PATRICIA): final analysis of a double-blind, randomised study in young women. Lancet 2009;374:301-14.
Milojkovic M. Residual and recurrent lesions after conization for cervical intraepithelial neoplasia grade 3. Int J Gynaecol Obstet 2002;76:49-53.
Skjeldestad FE, Hagen B, Lie AK, et al. Residual and recurrent disease after laser conization for cervical intraepithelial neoplasia. Obstet Gynecol 1997;90:428-33.
Herfs M, Yamamoto Y, Laury A, et al. A discrete population of squamocolumnar junction cells implicated in the pathogenesis of cervical cancer. Proc Natl Acad Sci USA 2012;109:10516-21.
Herfs M, Vargas SO, Yamamoto Y, et al. A novel blueprint for 'top down' differentiation defines the cervical squamocolumnar junction during development, reproductive life, and neoplasia. J Pathol 2013;229:460-8.
Wang X, Ouyang H, Yamamoto Y, et al. Residual embryonic cells as precursors of a Barrett's-like metaplasia. Cell 2011;145:1023-35.
Herfs M, Parra-Herran C, Howitt BE, et al. Cervical squamocolumnar junction-specific markers define distinct, clinically relevant subsets of lowgrade squamous intraepithelial lesions. Am J Surg Pathol 2013;37:1311-8.
Mo LZ, Monnier-Benoit S, Kantelip B, et al. Comparison of AMPLICOR and Hybrid Capture II assays for high risk HPV detection in normal and abnormal liquid-based cytology: use of INNO-LiPA Genotyping assay to screen the discordant results. J Clin Virol 2008;41:104-10.
Herfs M, Hubert P, Poirrier AL, et al. Proinflammatory cytokines induce bronchial hyperplasia and squamous metaplasia in smokers: implications for chronic obstructive pulmonary disease therapy. Am J Respir Cell Mol Biol 2012;47:67-9.
Wright TC Jr, Massad LS, Dunton CJ, et al. 2006 Consensus guidelines for the management of women with cervical intraepithelial neoplasia or adenocarcinoma in situ. Am J Obstet Gynecol 2007;197:340-5.
Wright TC Jr, Massad LS, Dunton CJ, et al. 2006 Consensus guidelines for the management of women with abnormal cervical cancer screening tests. Am J Obstet Gynecol 2007;197:346-55.
Gök M, Coupé VM, Berkhof J, et al. HPV16 and increased risk of recurrence after treatment for CIN. Gynecol Oncol 2007;104:273-5.
Van Der Marel J, Van Baars R, Alonso I, et al. Oncogenic human papillomavirus-infected immature metaplastic cells and cervical neoplasia. Am J Surg Pathol 2014;38:470-9.
Prato B, Ghelardi A, Gadducci A, et al. Correlation of recurrence rates and times with posttreatment human papillomavirus status in patients treated with loop electrosurgical excision procedure conization for cervical squamous intraepithelial lesions. Int J Gynecol Cancer 2008;18:90-4.
Bais AG, Eijkemans MJ, Rebolj M, et al. Posttreatment CIN: randomized clinical trial using hrHPV testing for prediction of residual/recurrent disease. Int J Cancer 2009;124:889-95.
Kocken M, Helmerhorst TJ, Berkhof J, et al. Risk of recurrent high-grade cervical intraepithelial neoplasia after successful treatment: a long-term multi-cohort study. Lancet Oncol 2011;12:441-50.
Strander B, Hällgren J, Spáren P. Effect of ageing on cervical or vaginal cancer in Swedish women previously treated for cervical intraepithelial neoplasia grade 3: population based cohort study of long term incidence and mortality. Br Med J 2014;348:f7361
Petry KU, Scheffel D, Bode U, et al. Cellular immunodeficiency enhances the progression of human papillomavirus-associated cervical lesions. Int J Cancer 1994;57:836-40.
Lima MI, Tafuri A, Araújo AC, et al. Cervical Intraepithelial neoplasia recurrence after conization in HIV-positive and HIV-negative women. Int J Gynaecol Obstet 2009;104:100-4.
Lodi CT, Michelin MA, Lima MI, et al. Factors associated with recurrence of cervical intraepithelial neoplasia after conization in HIV-infected and noninfected women. Arch Gynecol Obstet 2011;284:191-7.
McAllum B, Sykes PH, Sadler L, et al. Is the treatment of CIN 2 always necessary in women under 25 years old? Am J Obstet Gynecol 2011;205:478-7.
Moscicki AB, Ma Y, Wibbelsman C, et al. Rate of and risks for regression of cervical intraepithelial neoplasia 2 in adolescents and young women. Obstet Gynecol 2010;116:1373-80.
Taylor S, Wang C, Wright TC, et al. Reduced acquisition and reactivation of human papillomavirus infections among older women treated with cryotherapy: results from a randomized trial in South Africa. Biomed Chromatogr Med 2010;8:40.
Younge PA. Cancer of the uterine cervix; a preventable disease. Obstet Gynecol 1957;10:469-81.