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Covariates of high-risk human papillomavirus (HPV) infections are distinct for incident CIN1, CIN2 and CIN3 as disclosed by competing-risks regression models

  • K. SYRJÄNEN1,*,
  • I. Shabalova2
  • L. Sarian3
  • P. Naud4,5
  • A. Longatto-Filho6,7
  • S. Derchain3
  • V. Kozachenko2
  • S. Zakharchenko8
  • C. Roteli-Martins9
  • R. Nerovjna10
  • L. Kljukina11
  • S. Tatti12
  • M. Branovskaja13
  • M. Branca14
  • V. Grunjberga15,16
  • M. Eržen17
  • A. Juschenko15,16
  • L. Serpa Hammes4,5
  • J. Podistov18
  • S. Costa19
  • S. Syrjänen20
  • the NIS21
  • LAMS study research groups22

1Department of Oncology & Radiotherapy, Turku University Hospital, Turku, Finland

2Russian Academy of Post-Graduate Medical Education, Moscow, Russia

3Universidade Estadual de Campinas, Campinas, Brazil

4Hospital de Clinicas de Porto Alegre, Porto Alegre, RS, Braziland

5Department of Gynecology and Obstetrics, Federal University of Rio Grande do Sul, Porto Alegre, Brazil

6Laboratory of Medical Investigation (LIM14), Department of Pathology, Faculty of Medicine, São Paulo University, São Paulo University, São Paulo, Brazil

7Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal

8Novgorod Municipal Dermato-venereological Dispensary, Department of Gynaecology, Novgorod, Russia

9Hospital Leonor M de Barros, Sao Paulo, Brazil

10Novgorod Female Consultative Outpatient Hospital, Department of Gynaecology, Novgorod, Russia

11Research Institute of Oncology and Medical Radiology, Republican Centre of Clinical Cytology, Minsk, Belarus

12First Chair Gynecology Hospital de Clinicas, Buenos Aires, Argentina

13Minsk State Medical Institute, Department of Gynaecology and Obstetrics, Minsk, Belarus

14Unit of Cytopathology, National Centre of Epidemiology, Surveillance and Promotion of Health, National Institute of Health (ISS), Rome, Italy

15Latvian Cancer Centre, Department of Gynaecology, Riga, Latvia

16Laboratory of Cytology, Riga, Latvia

17SIZE Diagnostic Center, Ljubljana, Slovenia

18N.N. Blokhin Cancer Research Centre of Russian Academy of Medical Sciences (RAMS), Moscow, Russia

19Department of Obstetrics and Gynecology, S. Orsola-Malpighi Hospital, Bologna, Italy

20Department of Oral Pathology, Institute of Dentistry, University of Turku, SF-20500 Turku, Finland

21,New Independent States of the Former Soviet Union

22,Latin American Screening Study

DOI: 10.12892/ejgo20120105 Vol.33,Issue 1,January 2012 pp.5-14

Published: 10 January 2012

*Corresponding Author(s): K. SYRJÄNEN E-mail: kari.syrjanen@tyks.fi

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 competing-risks 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 GIN I, 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 GIN, which revisits the concept of combining CIN2 with CIN3 or with CIN1 in histological classification or used as a common end-point, e.g., in HPV vaccine trials.

Keywords

CIN; HPV; Covariates; Progression; Competing-risks regression; Univariate; Multivariate; Prospective follow-up; NIS Cohort; LAMS Study

Cite and Share

K. SYRJÄNEN,I. Shabalova,L. Sarian,P. Naud,A. Longatto-Filho,S. Derchain,V. Kozachenko,S. Zakharchenko,C. Roteli-Martins,R. Nerovjna,L. Kljukina,S. Tatti,M. Branovskaja,M. Branca,V. Grunjberga,M. Eržen,A. Juschenko,L. Serpa Hammes,J. Podistov,S. Costa,S. Syrjänen,the NIS,LAMS study research groups. Covariates of high-risk human papillomavirus (HPV) infections are distinct for incident CIN1, CIN2 and CIN3 as disclosed by competing-risks regression models. European Journal of Gynaecological Oncology. 2012. 33(1);5-14.

References

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