High load for most high risk human papillomavirus genotypes is associated with prevalent cervical cancer precursors but only HPV16 load predicts the development of incident disease

Patti E. Gravitt, Melinda Butsch Kovacic, Rolando Herrero, Mark Schiffman, Concepcion Bratti, Allan Hildesheim, Jorge Morales, Mario Alfaro, Mark E. Sherman, Sholom Wacholder, Ana Cecilia Rodriguez, Robert D. Burk

Research output: Contribution to journalArticle

112 Citations (Scopus)

Abstract

Cervicovaginal human papillomavirus (HPV) viral load has been purported as a potential marker for the detection of high-grade cervical intraepithelial neoplasia or cancer (≥CIN2). To examine disease association with type-specific viral load for the full-range of anogenital HPV infections, we conducted cross-sectional and prospective analyses of ∼2,000 HPV-infected women from a 10,000-woman population-based study in Guanacaste, Costa Rica with 7 years of follow-up. Cervical specimens were tested for >40 HPV types using a MY09/MY11 L1 consensus primer PCR method with type-specific dot blot hybridization and PCR signal intensity as a measure of viral load. A positive association was observed between prevalent ≥CIN2 and high viral load compared to low viral load for women with baseline single HPV16 infections (OR = 19.2, 95% CI = 4.4-83.2) and single non-16 carcinogenic infections (OR = 9.2, 95% CI = 2.1-39.9). Inclusion of women with multiple HPV types did not substantially change these associations. In prospective follow-up, only women infected with HPV16 alone (OR = 27.2, 95% = 3.5-213.5) had a strong association between high viral load and incident ≥CIN2; non-16 carcinogenic high viral load was not associated with incident ≥CIN2 (OR = 0.7, 95% CI = 0.2-1.9). Single noncarcinogenic type viral load was not associated with increased risk of prevalent or incident ≥CIN2 (OR = 1.2 and 1.1, respectively). In conclusion, carcinogenic high viral load was associated with prevalent ≥CIN2; however HPV16 was uniquely associated with incident ≥CIN2. The extent to which these observations can be translated into clinical practice must be rigorously examined in the context of the method of viral load measurement and the type-specific differences observed for incident ≥CIN2.

Original languageEnglish (US)
Pages (from-to)2787-2793
Number of pages7
JournalInternational Journal of Cancer
Volume121
Issue number12
DOIs
StatePublished - Nov 15 2007

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Viral Load
Uterine Cervical Neoplasms
Genotype
Costa Rica
Polymerase Chain Reaction
Cervical Intraepithelial Neoplasia
Papillomavirus Infections
Infection
Cross-Sectional Studies

Keywords

  • Genotype
  • Human papillomavirus
  • Screening
  • Viral load

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

High load for most high risk human papillomavirus genotypes is associated with prevalent cervical cancer precursors but only HPV16 load predicts the development of incident disease. / Gravitt, Patti E.; Kovacic, Melinda Butsch; Herrero, Rolando; Schiffman, Mark; Bratti, Concepcion; Hildesheim, Allan; Morales, Jorge; Alfaro, Mario; Sherman, Mark E.; Wacholder, Sholom; Rodriguez, Ana Cecilia; Burk, Robert D.

In: International Journal of Cancer, Vol. 121, No. 12, 15.11.2007, p. 2787-2793.

Research output: Contribution to journalArticle

Gravitt, PE, Kovacic, MB, Herrero, R, Schiffman, M, Bratti, C, Hildesheim, A, Morales, J, Alfaro, M, Sherman, ME, Wacholder, S, Rodriguez, AC & Burk, RD 2007, 'High load for most high risk human papillomavirus genotypes is associated with prevalent cervical cancer precursors but only HPV16 load predicts the development of incident disease', International Journal of Cancer, vol. 121, no. 12, pp. 2787-2793. https://doi.org/10.1002/ijc.23012
Gravitt, Patti E. ; Kovacic, Melinda Butsch ; Herrero, Rolando ; Schiffman, Mark ; Bratti, Concepcion ; Hildesheim, Allan ; Morales, Jorge ; Alfaro, Mario ; Sherman, Mark E. ; Wacholder, Sholom ; Rodriguez, Ana Cecilia ; Burk, Robert D. / High load for most high risk human papillomavirus genotypes is associated with prevalent cervical cancer precursors but only HPV16 load predicts the development of incident disease. In: International Journal of Cancer. 2007 ; Vol. 121, No. 12. pp. 2787-2793.
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abstract = "Cervicovaginal human papillomavirus (HPV) viral load has been purported as a potential marker for the detection of high-grade cervical intraepithelial neoplasia or cancer (≥CIN2). To examine disease association with type-specific viral load for the full-range of anogenital HPV infections, we conducted cross-sectional and prospective analyses of ∼2,000 HPV-infected women from a 10,000-woman population-based study in Guanacaste, Costa Rica with 7 years of follow-up. Cervical specimens were tested for >40 HPV types using a MY09/MY11 L1 consensus primer PCR method with type-specific dot blot hybridization and PCR signal intensity as a measure of viral load. A positive association was observed between prevalent ≥CIN2 and high viral load compared to low viral load for women with baseline single HPV16 infections (OR = 19.2, 95{\%} CI = 4.4-83.2) and single non-16 carcinogenic infections (OR = 9.2, 95{\%} CI = 2.1-39.9). Inclusion of women with multiple HPV types did not substantially change these associations. In prospective follow-up, only women infected with HPV16 alone (OR = 27.2, 95{\%} = 3.5-213.5) had a strong association between high viral load and incident ≥CIN2; non-16 carcinogenic high viral load was not associated with incident ≥CIN2 (OR = 0.7, 95{\%} CI = 0.2-1.9). Single noncarcinogenic type viral load was not associated with increased risk of prevalent or incident ≥CIN2 (OR = 1.2 and 1.1, respectively). In conclusion, carcinogenic high viral load was associated with prevalent ≥CIN2; however HPV16 was uniquely associated with incident ≥CIN2. The extent to which these observations can be translated into clinical practice must be rigorously examined in the context of the method of viral load measurement and the type-specific differences observed for incident ≥CIN2.",
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