IMR Press / EJGO / Volume 33 / Issue 1 / pii/1631086190661-719968731

European Journal of Gynaecological Oncology (EJGO) is published by IMR Press from Volume 40 Issue 1 (2019). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with S.O.G.

Open Access Distinguished Expert Series
Covariates of high-risk human papillomavirus (HPV) infections are distinct for incident CIN1, CIN2 and CIN3 as disclosed by competing-risks regression models
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1 Department of Oncology & Radiotherapy, Turku University Hospital, Turku (Finland)
1 *NIS, New Independent States of the Former Soviet Union; **LAMS, Latin American Screening Study
2 Russian Academy of Post-Graduate Medical Education, Moscow (Russia)
3 Universidade Estadual de Campinas, Campinas (Brazil)
4 Hospital de Clinicas de Porto Alegre, and Department of Gynecology and Obstetrics, Federal University of Rio Grande do Sul, Porto Alegre (Brazil)
5 Laboratory of Medical Investigation (LIM14), Department of Pathology, Faculty of Medicine, São Paulo University, São Paulo University, São Paulo (Brazil); and Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga (Portugal)
6 Novgorod Municipal Dermato-venereological Dispensary, Department of Gynaecology, Novgorod (Russia)
7 Hospital Leonor M de Barros, Sao Paulo (Brazil)
8 Novgorod Female Consultative Outpatient Hospital, Department of Gynaecology, Novgorod, Russia
9 Research Institute of Oncology and Medical Radiology, Republican Centre of Clinical Cytology, Minsk (Belarus)
10 First Chair Gynecology Hospital de Clinicas, Buenos Aires, Argentina
11 Minsk State Medical Institute, Department of Gynaecology and Obstetrics, Minsk (Belarus)
12 Unit of Cytopathology, National Centre of Epidemiology, Surveillance and Promotion of Health, National Institute of Health (ISS), Rome (Italy)
13 Latvian Cancer Centre, Department of Gynaecology, and Laboratory of Cytology, Riga (Latvia)
14 SIZE Diagnostic Center, Ljubljana, Slovenia
15 N.N. Blokhin Cancer Research Centre of Russian Academy of Medical Sciences (RAMS), Moscow (Russia)
16 Department of Obstetrics and Gynecology, S. Orsola-Malpighi Hospital, Bologna (Italy)
17 Department of Oral Pathology, Institute of Dentistry, University of Turku (Finland).
Eur. J. Gynaecol. Oncol. 2012, 33(1), 5–14;
Published: 10 February 2012
Abstract

Background: In addition to the oncogenic human papillomavirus (HPV), several cofactors are needed in cervical carcinogenesis, but whether the HPV covariates associated with incident i) CIN1 are different from those of incident ii) CIN2 and iii) CIN3 needs further assessment. Objectives: To gain further insights into the true biological differences between CIN1, CIN2 and CIN3, we assessed HPV covariates associated with incident CIN1, CIN2, and CIN3. Study Design and Methods: HPV covariates associated with progression to CIN1, CIN2 and CIN3 were analysed in the combined cohort of the NIS (n = 3,187) and LAMS study (n = 12,114), using competingrisks regression models (in panel data) for baseline HR-HPV-positive women (n = 1,105), who represent a sub-cohort of all 1,865 women prospectively followed-up in these two studies. Results: Altogether, 90 (4.8%), 39 (2.1%) and 14 (1.4%) cases progressed to CIN1, CIN2, and CIN3, respectively. Among these baseline HR-HPV-positive women, the risk profiles of incident CIN1, CIN2 and CIN3 were unique in that completely different HPV covariates were associated with progression to CIN1, CIN2 and CIN3, irrespective which categories (non-progression, CIN1, CIN2, CIN3 or all) were used as competing-risks events in univariate and multivariate models. Conclusions: These data confirm our previous analysis based on multinomial regression models implicating that distinct covariates of HR-HPV are associated with progression to CIN1, CIN2 and CIN3. This emphasises true biological differences between the three grades of CIN, which revisits the concept of combining CIN2 with CIN3 or with CIN1 in histological classification or used as a common endpoint, e.g., in HPV vaccine trials.
Keywords
CIN
HPV
Covariates
Progression
Competing-risks regression
Univariate
Multivariate
Prospective follow-up
NIS Cohort
LAMS Study
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