Relationships of Human Papillomavirus Type, Qualitative Viral Load, and Age with Cytologic Abnormality

Melinda Butsch Kovacic, Philip E. Castle, Rolando Herrero, Mark Schiffman, Mark E. Sherman, Sholom Wacholder, Ana C. Rodriguez, Martha L. Hutchinson, M. Concepción Bratti, Allan Hildesheim, Jorge Morales, Mario Alfaro, Robert D. Burk

Research output: Contribution to journalArticle

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Abstract

Persistent cervical infections with carcinogenic human papillomaviruses (HPV) cause virtually all cervical cancer. Cytologic abnormalities are the manifestations of HPV infections used to identify women at risk. To compare the potential of the full range of anogenital HPV genotypes to induce cytopathic effects, we examined the influences of HPV type, viral load, and age on cytopathology among 1,222 women having a single HPV type at enrollment into a 10,000-woman population-based study in Costa Rica. Cervical specimens were tested for -40 HPV types by MY09/MY11 L1 primer PCR and type-specific dot blot hybridization. Types were organized by phylogenetic species and cancer risk. PCR signal strength served as a qualitative surrogate for viral load. Overall, 24.8% [95% confidence interval (95% Cl), 22.4-27.3] of single prevalent HPV infections had concurrent abnormalities (atypical squamous cells or worse) ranging from 0.0% to 80.0% based on HPV type. Noncarcinogenic α3/α15 types, although highly prevalent, uncommonly caused cytologic abnormalities (13.1%; 95% CI, 9.8-17.0). In contrast, one quarter to nearly one half of infections with a single major carcinogenic species type (α9/α11/ α7/α5/α6) produced abnormalities. Greater abnormalities were observed with increasing qualitative viral load of carcinogenic types; fewer abnormalities were observed among older women (>54 years). A high percentage (46.2%) of detected abnormalities in women infected with HPV16 or related α9 types were high grade or worse, consistent with strong carcinogenicity, compared with 10.7% in women infected with α7 types, including HPV18, a major cause of adenocarcinoma. The lack of evident severe abnormalities associated with HPV18 and related HPV types might have implications for screening for poorly detected glandular and α7-related lesions.

Original languageEnglish (US)
Pages (from-to)10112-10119
Number of pages8
JournalCancer Research
Volume66
Issue number20
DOIs
StatePublished - Oct 15 2006

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Viral Load
Papillomavirus Infections
Costa Rica
Polymerase Chain Reaction
Infection
Uterine Cervical Neoplasms
Adenocarcinoma
Genotype
Confidence Intervals
Population

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Relationships of Human Papillomavirus Type, Qualitative Viral Load, and Age with Cytologic Abnormality. / Kovacic, Melinda Butsch; Castle, Philip E.; Herrero, Rolando; Schiffman, Mark; Sherman, Mark E.; Wacholder, Sholom; Rodriguez, Ana C.; Hutchinson, Martha L.; Concepción Bratti, M.; Hildesheim, Allan; Morales, Jorge; Alfaro, Mario; Burk, Robert D.

In: Cancer Research, Vol. 66, No. 20, 15.10.2006, p. 10112-10119.

Research output: Contribution to journalArticle

Kovacic, MB, Castle, PE, Herrero, R, Schiffman, M, Sherman, ME, Wacholder, S, Rodriguez, AC, Hutchinson, ML, Concepción Bratti, M, Hildesheim, A, Morales, J, Alfaro, M & Burk, RD 2006, 'Relationships of Human Papillomavirus Type, Qualitative Viral Load, and Age with Cytologic Abnormality', Cancer Research, vol. 66, no. 20, pp. 10112-10119. https://doi.org/10.1158/0008-5472.CAN-06-1812
Kovacic, Melinda Butsch ; Castle, Philip E. ; Herrero, Rolando ; Schiffman, Mark ; Sherman, Mark E. ; Wacholder, Sholom ; Rodriguez, Ana C. ; Hutchinson, Martha L. ; Concepción Bratti, M. ; Hildesheim, Allan ; Morales, Jorge ; Alfaro, Mario ; Burk, Robert D. / Relationships of Human Papillomavirus Type, Qualitative Viral Load, and Age with Cytologic Abnormality. In: Cancer Research. 2006 ; Vol. 66, No. 20. pp. 10112-10119.
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abstract = "Persistent cervical infections with carcinogenic human papillomaviruses (HPV) cause virtually all cervical cancer. Cytologic abnormalities are the manifestations of HPV infections used to identify women at risk. To compare the potential of the full range of anogenital HPV genotypes to induce cytopathic effects, we examined the influences of HPV type, viral load, and age on cytopathology among 1,222 women having a single HPV type at enrollment into a 10,000-woman population-based study in Costa Rica. Cervical specimens were tested for -40 HPV types by MY09/MY11 L1 primer PCR and type-specific dot blot hybridization. Types were organized by phylogenetic species and cancer risk. PCR signal strength served as a qualitative surrogate for viral load. Overall, 24.8{\%} [95{\%} confidence interval (95{\%} Cl), 22.4-27.3] of single prevalent HPV infections had concurrent abnormalities (atypical squamous cells or worse) ranging from 0.0{\%} to 80.0{\%} based on HPV type. Noncarcinogenic α3/α15 types, although highly prevalent, uncommonly caused cytologic abnormalities (13.1{\%}; 95{\%} CI, 9.8-17.0). In contrast, one quarter to nearly one half of infections with a single major carcinogenic species type (α9/α11/ α7/α5/α6) produced abnormalities. Greater abnormalities were observed with increasing qualitative viral load of carcinogenic types; fewer abnormalities were observed among older women (>54 years). A high percentage (46.2{\%}) of detected abnormalities in women infected with HPV16 or related α9 types were high grade or worse, consistent with strong carcinogenicity, compared with 10.7{\%} in women infected with α7 types, including HPV18, a major cause of adenocarcinoma. The lack of evident severe abnormalities associated with HPV18 and related HPV types might have implications for screening for poorly detected glandular and α7-related lesions.",
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