The HPV16 Genome Is Stable in Women Who Progress to In Situ or Invasive Cervical Cancer: A Prospective Population-Based Study

Cancer Res. 2019 Sep 1;79(17):4532-4538. doi: 10.1158/0008-5472.CAN-18-3933. Epub 2019 Jul 9.


The human papillomavirus (HPV) rate of evolution is essential for cancer-preventive strategies targeting HPV. We analyzed variability over time in a prospective, population-based nested case-control study of in situ (CIS) and invasive squamous cervical cancer (SCC). Among 757,690 women who participated in cervical screening in Sweden during 1969 to 2002, we identified 94 women who had HPV16 persistence in two serial cervical screening samples (median 24 months apart, range 0.5-178 months) and later were diagnosed with CIS (n = 59), SCC (n = 32), or remained healthy (n = 3). Whole-HPV16-genome sequencing and comparison of sequences in the serial samples revealed that all women had the same HPV16 lineage, particularly lineage A, in both serial smears. Fifty-six percent of women had an identical 7,906 base pair HPV16 sequence in both samples, and no woman had more than 15 nucleotide substitutions. The median substitution rate was 0 substitutions/site/year (95% confidence interval, 0-0.00008), with no variation between quartiles of follow-up. We concluded that in most women with HPV16 persistence preceding disease, the nucleotide substitution rate was not measurable within up to 15-years follow-up. This slow rate of evolution has important implications for both HPV-based screening and HPV vaccination. SIGNIFICANCE: These findings show there is no genomic variation over time in HPV16 infections progressing to cervical cancer, which could influence risk stratification of women when screening for cervical cancer and inform HPV vaccination strategies.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Case-Control Studies
  • Coinfection / virology
  • Female
  • Genetic Variation
  • Genome, Viral*
  • High-Throughput Nucleotide Sequencing
  • Human papillomavirus 16 / genetics*
  • Humans
  • Middle Aged
  • Papillomavirus Infections / genetics*
  • Polymorphism, Single Nucleotide
  • Prospective Studies
  • Reproducibility of Results
  • Uterine Cervical Neoplasms / virology*