Effect of Pap smear collection and carrageenan on cervicovaginal human papillomavirus-16 infection in a rhesus macaque model

J Natl Cancer Inst. 2011 May 4;103(9):737-43. doi: 10.1093/jnci/djr061. Epub 2011 Apr 11.


Background: Human papillomavirus (HPV) infection of the genital mucosa is thought to require trauma to the cervicovaginal epithelium. Therefore, we determined whether a cytology specimen collection procedure (Pap smear), which disrupts the epithelium by design, renders the cervix more susceptible to HPV infection in a primate model.

Methods: In a series of female rhesus macaques, a speculum examination was performed with (n = 8) or without (n = 4) a cytology specimen collection procedure as it is commonly practiced in a gynecology clinic. An internal digital examination was performed after specimen collection using Surgilube (n = 4) or 1% iota-carrageenan, a previously indentified HPV inhibitor (n = 4) as the lubricant. The cervix was then inoculated with HPV16 pseudovirions expressing red fluorescent protein. After 3 days, the reproductive tracts were excised and the cervix was cryosectioned. Sections were analyzed by fluorescent confocal microscopy for the number of red fluorescent protein-positive keratinocytes.

Results: Substantial infection of the ectocervix, the transformation zone, and the endocervix was detected, but only in conjunction with the cytology specimen collection procedure (cytology using Surgilube vs without cytology using Surgilube, mean = 84 infectious events per section vs mean = 0.05 infectious events per section, difference = 84 infectious events per section, 95% confidence interval = 19 to 384 infectious events per section). When the carrageenan gel was substituted for Surgilube for an internal digital examination, the mean number of infectious events decreased (carrageenan gel vs Surgilube, mean = 3.5 events per section vs mean = 84 infectious events per section difference = 81 events per section, 95% confidence interval = 33 to 213 events per section).

Conclusions: These findings indicate that cytology screening in women might lead to a transient enhancement of susceptibility to HPV infection and that use of a carrageenan-based gel during the examination might mitigate this enhancement.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Anti-Infective Agents, Local*
  • Carrageenan*
  • Cervix Uteri / virology*
  • Disease Models, Animal
  • Disease Susceptibility
  • Female
  • Gels
  • Gene Expression Regulation, Viral
  • Human papillomavirus 16 / isolation & purification*
  • Human papillomavirus 16 / metabolism
  • Humans
  • Keratinocytes / chemistry
  • Luminescent Proteins / analysis
  • Macaca mulatta
  • Microscopy, Confocal
  • Microscopy, Fluorescence
  • Papanicolaou Test*
  • Papillomavirus Infections / etiology*
  • Papillomavirus Infections / pathology
  • Papillomavirus Infections / prevention & control*
  • Papillomavirus Infections / virology
  • Phenylmercury Compounds*
  • Risk Factors
  • Tumor Virus Infections / etiology*
  • Tumor Virus Infections / pathology
  • Tumor Virus Infections / prevention & control*
  • Tumor Virus Infections / virology
  • Uterine Cervical Neoplasms / prevention & control
  • Uterine Cervical Neoplasms / virology
  • Vaginal Smears / adverse effects*
  • Vaginal Smears / methods*
  • Virion


  • Anti-Infective Agents, Local
  • Gels
  • Luminescent Proteins
  • Phenylmercury Compounds
  • red fluorescent protein
  • Carrageenan
  • phenylmercury borate