Variant-specific persistence of infections with human papillomavirus Types 31, 33, 45, 56 and 58 and risk of cervical intraepithelial neoplasia

Int J Cancer. 2016 Sep 1;139(5):1098-105. doi: 10.1002/ijc.30164. Epub 2016 May 14.

Abstract

In our previous study of the etiologic role of oncogenic human papillomavirus (HPV) types other than HPV16 and 18, we observed a significantly higher risk of cervical intraepithelial neoplasia Grades 2-3 (CIN2/3) associated with certain lineages of HPV types 31/33/45/56/58 [called high-risk (HR) variants] compared with non-HR variants. This study was to examine whether these intra-type variants differ in persistence of the infection and persistence-associated risk of CIN2/3. Study subjects were women who had any of HPV types 31/33/45/56/58 newly detected during a 2-year follow-up with 6-month intervals. For each type, the first positive sample was used for variant characterization. The association of reverting-to-negativity with group of the variants and CIN2/3 with length of positivity was assessed using discrete Cox regression and logistic regression, respectively. Of the 598 newly detected, type-specific HPV infections, 312 became undetectable during follow-up. Infections with HR, compared with non-HR, variants were marginally more likely to become negative [adjusted hazard ratio = 1.3; 95% confidence interval (CI), 0.9-1.8]. The adjusted odds ratio associating with the development of CIN2/3 was 3.0 (95% CI, 1.2-7.4) for persistent infections with HR variants for 6 months and 10.0 (95% CI, 3.8-38.0) for persistent infections with HR variants for 12-18 months as compared with the first positive detection of HR variants. Among women with non-HR variants, there were no appreciable differences in risk of CIN2/3 by length of positivity. Findings suggest that the lineage-associated risk of CIN2/3 was not mediated through a prolonged persistent infection, but oncogenic heterogeneity of the variants.

Keywords: cervical intraepithelial neoplasia; human papillomavirus; persistence; variants.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Follow-Up Studies
  • Humans
  • Kaplan-Meier Estimate
  • Neoplasm Grading
  • Papillomaviridae* / classification
  • Papillomavirus Infections / complications*
  • Papillomavirus Infections / virology*
  • Proportional Hazards Models
  • Randomized Controlled Trials as Topic
  • Uterine Cervical Dysplasia / epidemiology*
  • Uterine Cervical Dysplasia / etiology*
  • Uterine Cervical Dysplasia / pathology