title: Co-factors of high-risk human papillomavirus infections display unique profiles in incident CIN1, CIN2 and CIN3.
abstract: In addition to oncogenic 'high-risk' human papillomaviruses (HR-HPV), several co-factors are needed in cervical carcinogenesis, but it is poorly understood whether these HPV co-factors associated with incident cervical intraepithelial neoplasia (CIN) grade 1 are different from those required for progression to CIN2 and CIN3. To gain further insights into the true biological differences between CIN1, CIN2 and CIN3, we assessed HPV co-factors increasing the risk of incident CIN1, CIN2 and CIN3. Data from the New Independent States of the Former Soviet Union (NIS) Cohort (n = 3187) and the Latin American Screening (LAMS) Study (n = 12,114) were combined, and co-factors associated with progression to CIN1, CIN2 and CIN3 were analysed using multinomial logistic regression models with all covariates recorded at baseline. HR-HPV-positive women (n = 1105) represented a subcohort of all 1865 women prospectively followed up in both studies. Altogether, 90 (4.8%), 39 (2.1%) and 14 (1.4%) cases progressed to CIN1, CIN2 and CIN3, respectively. Baseline HR-HPV was the single most powerful predictor of incident CIN1, CIN2 and CIN3. When controlled for residual HPV confounding by analysing HR-HPV-positive women only, the risk profiles of incident CIN1, CIN2 and CIN3 were unique. Completely different HPV co-factors were associated with progression to CIN1, CIN2 and CIN3 in univariate and multivariate analyses, irrespective of whether non-progression, CIN1 or CIN2 was used as the reference outcome. HPV co-factors associated with progression to CIN1, CIN2 and CIN3 display unique profiles, implicating genuine biological differences between the three CIN grades, which prompts us to re-visit the concept of combining CIN2 with CIN3 or CIN1.
authors.affiliation: Department of Oncology and Radiotherapy, Turku University Hospital, Savitehtaankatu 1, 20521 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: P
authors.initials: P
authors.lastname: Naud
authors.forename: S
authors.initials: S
authors.lastname: Derchain
authors.forename: L
authors.initials: L
authors.lastname: Sarian
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: A
authors.initials: A
authors.lastname: Longatto-Filho
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 Serpa
authors.initials: LS
authors.lastname: Hammes
authors.forename: S
authors.initials: S
authors.lastname: Costa
authors.forename: J
authors.initials: J
authors.lastname: Podistov
authors.forename: S
authors.initials: S
authors.lastname: Syrjänen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D015994:Incidence; D007843:Latin America / Q000453:epidemiology; D008875:Middle Aged; D027383:Papillomaviridae / Q000302:isolation & purification*; D030361:Papillomavirus Infections / Q000150:complications / Q000453:epidemiology* / Q000821:virology*; D012307:Risk Factors; D014586:USSR / Q000453:epidemiology; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000453:epidemiology* / Q000473:pathology / Q000821:virology*