No Evidence for Synergy Between Human Papillomavirus Genotypes for the Risk of High-Grade Squamous Intraepithelial Lesions in a Large Population-Based Study

J Infect Dis. 2014 Mar;209(6):855-64. doi: 10.1093/infdis/jit577. Epub 2013 Oct 31.


Background: Multiple human papillomavirus (HPV) genotypes may be independently or synergistically associated with risk of high-grade squamous intraepithelial lesions (HSILs). We evaluated the risk of HSIL in women concomitantly infected with multiple HPV genotypes.

Methods: A population-based stratified sample of 59 664 cervical cytology specimens from women residing in New Mexico were evaluated for cytologic abnormalities and HPV genotypes. We calculated the risk of HSIL in women infected with a single HPV genotype and the risk in those infected with multiple HPV genotypes.

Results: The highest risk of HSIL was observed for HPV-16 (0.036), followed by HPV-33 (0.028), HPV-58 (0.024), and HPV-18 (0.022). For most types, we observed a greater risk of HSIL in women infected with multiple carcinogenic HPV types. In contrast, the risk of HSIL was similar in women infected with HPV-16 and other types, compared with women infected with HPV-16 only. We observed an increased but plateauing risk of HSIL in women infected with multiple types, compared with those infected with a single type, with risk ratios of 1.5 (95% confidence interval [CI], 1.2-1.8), 1.7 (95% CI, 1.3-2.4), and 1.4 (95% CI, 0.83-2.5) for women infected with 2, 3, and ≥4 genotypes, respectively.

Conclusions: In the largest population-based study of HPV genotypes and cytologic outcomes so far, we did not see more than additive effects of HPV types on the risk of HSIL in women infected with multiple types.

Keywords: cervical cancer screening; cytology; human papillomavirus (HPV); multiple Infections.

MeSH terms

  • Adult
  • Cervical Intraepithelial Neoplasia / epidemiology
  • Cervical Intraepithelial Neoplasia / virology*
  • Cervix Uteri / virology
  • Coinfection / epidemiology
  • Coinfection / virology
  • Cross-Sectional Studies
  • Early Detection of Cancer
  • Female
  • Humans
  • Logistic Models
  • New Mexico / epidemiology
  • Papillomaviridae / genetics*
  • Papillomaviridae / isolation & purification
  • Papillomavirus Infections / epidemiology
  • Papillomavirus Infections / virology*
  • Uterine Cervical Neoplasms / epidemiology
  • Uterine Cervical Neoplasms / virology*