title: Covariates of high-risk human papillomavirus (HPV) infections are distinct for incident CIN1, CIN2 and CIN3 as disclosed by competing-risks regression models.
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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  HPV covariates associated with progression to CIN1, CIN2 and CIN3 were analysed in the combined cohort of the NIS (n = 3187) and LAMS study (n = 12,114), using competing-risks regression models (in panel data) for baseline HR-HPV-positive women (n = 1105), who represent a sub-cohort of all 1865 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.
authors.affiliation: Department of Oncology & Radiotherapy, Turku University Hospital, Turku, Finland. kari.syrjanen@tyks.fi
authors.forename: K
authors.initials: K
authors.lastname: Syrjänen
authors.forename: I
authors.initials: I
authors.lastname: Shabalova
authors.forename: L
authors.initials: L
authors.lastname: Sarian
authors.forename: P
authors.initials: P
authors.lastname: Naud
authors.forename: A
authors.initials: A
authors.lastname: Longatto-Filho
authors.forename: S
authors.initials: S
authors.lastname: Derchain
authors.forename: V
authors.initials: V
authors.lastname: Kozachenko
authors.forename: S
authors.initials: S
authors.lastname: Zakharchenko
authors.forename: C
authors.initials: C
authors.lastname: Roteli-Martins
authors.forename: R
authors.initials: R
authors.lastname: Nerovjna
authors.forename: L
authors.initials: L
authors.lastname: Kljukina
authors.forename: S
authors.initials: S
authors.lastname: Tatti
authors.forename: M
authors.initials: M
authors.lastname: Branovskaja
authors.forename: M
authors.initials: M
authors.lastname: Branca
authors.forename: V
authors.initials: V
authors.lastname: Grunjberga
authors.forename: M
authors.initials: M
authors.lastname: Erzen
authors.forename: A
authors.initials: A
authors.lastname: Juschenko
authors.forename: L
authors.initials: L
authors.lastname: Serpa Hammes
authors.forename: J
authors.initials: J
authors.lastname: Podistov
authors.forename: S
authors.initials: S
authors.lastname: Costa
authors.forename: S
authors.initials: S
authors.lastname: Syrjänen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003276:Contraceptives, Oral; D018450:Disease Progression; D005260:Female; D006801:Humans; D008875:Middle Aged; D015999:Multivariate Analysis; D030361:Papillomavirus Infections / Q000150:complications*; D012044:Regression Analysis; D012307:Risk Factors; D012907:Smoking; D002583:Uterine Cervical Neoplasms / Q000209:etiology* / Q000473:pathology* / Q000821:virology; D014626:Vaginal Smears; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000209:etiology* / Q000473:pathology* / Q000821:virology
chemical_list: D003276:Contraceptives, Oral