Epidemiologic and viral factors associated with cervical neoplasia in HPV-16-positive women

Mangalathu S. Rajeevan, David C. Swan, Rosane Nisenbaum, Daisy R. Lee, Suzanne D. Vernon, Mack T. Ruffin, Ira R. Horowitz, Lisa C. Flowers, David Kmak, Talaat Tadros, George Birdsong, Mujtaba Husain, Sudhir Srivastava, Elizabeth R. Unger

Research output: Contribution to journalArticle

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Abstract

While infection with high-risk HPV is the most important risk factor for cervical cancer, HPV alone is insufficient. Our purpose was to identify viral and epidemiologic factors associated with cervical disease in HPV-16 DNA-positive women referred to colposcopy. We used a standardized interview to collect epidemiologic data from consenting women. Total nucleic acids from exfoliated cervical cells were used for all viral assays (HPV detection and typing using L1 consensus PCR with line probe hybridization, variant classification by sequencing, viral load and transcript copy determination by quantitative PCR and transcript pattern by nested RT-PCR). Cervical disease was based on colposcopic biopsy. Logistic regression was used to calculate ORs with 95% CIs. There were 115 HPV-16 positive women among 839 enrollees. By univariate analyses, age >25 years (OR = 3.05, 95% CI 1.20-7.76), smoking (OR = 3.0, 95% CI 1.19-7.56), high viral load (OR = 5.27, 95% CI 2.05-13.60), detection of both E6 and E6*1 transcripts (OR = 10.0, 95% CI 2.1-47.58) and high transcript copies (OR = 5.56, 95% CI 2.05-13.60) were significant risk factors for CIN III with reference to No CIN/CIN I. Less than a third of the women (31.5%) had prototype HPV-16 detected, and variants showed no association with disease, viral load or transcription. Viral DNA and transcript copies were highly correlated, and the ratio of transcript copies to DNA copies was not changed with disease status. While viral load, transcript copies and transcript pattern were statistically associated with CIN III, none of these measures effectively discriminated between HPV-16 women with disease requiring treatment and those who could be followed. Cellular proliferation and differentiation pathways affected by HPV should be investigated as biomarkers for cervical cancer screening.

Original languageEnglish (US)
Pages (from-to)114-120
Number of pages7
JournalInternational Journal of Cancer
Volume115
Issue number1
DOIs
StatePublished - May 20 2005

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Epidemiologic Factors
Human papillomavirus 16
Viral Load
Neoplasms
Uterine Cervical Neoplasms
Polymerase Chain Reaction
Colposcopy
DNA
Viral DNA
Early Detection of Cancer
Nucleic Acids
Consensus
Biomarkers
Logistic Models
Smoking
Cell Proliferation
Interviews
Biopsy
Infection

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Rajeevan, M. S., Swan, D. C., Nisenbaum, R., Lee, D. R., Vernon, S. D., Ruffin, M. T., ... Unger, E. R. (2005). Epidemiologic and viral factors associated with cervical neoplasia in HPV-16-positive women. International Journal of Cancer, 115(1), 114-120. https://doi.org/10.1002/ijc.20894
Rajeevan, Mangalathu S. ; Swan, David C. ; Nisenbaum, Rosane ; Lee, Daisy R. ; Vernon, Suzanne D. ; Ruffin, Mack T. ; Horowitz, Ira R. ; Flowers, Lisa C. ; Kmak, David ; Tadros, Talaat ; Birdsong, George ; Husain, Mujtaba ; Srivastava, Sudhir ; Unger, Elizabeth R. / Epidemiologic and viral factors associated with cervical neoplasia in HPV-16-positive women. In: International Journal of Cancer. 2005 ; Vol. 115, No. 1. pp. 114-120.
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abstract = "While infection with high-risk HPV is the most important risk factor for cervical cancer, HPV alone is insufficient. Our purpose was to identify viral and epidemiologic factors associated with cervical disease in HPV-16 DNA-positive women referred to colposcopy. We used a standardized interview to collect epidemiologic data from consenting women. Total nucleic acids from exfoliated cervical cells were used for all viral assays (HPV detection and typing using L1 consensus PCR with line probe hybridization, variant classification by sequencing, viral load and transcript copy determination by quantitative PCR and transcript pattern by nested RT-PCR). Cervical disease was based on colposcopic biopsy. Logistic regression was used to calculate ORs with 95{\%} CIs. There were 115 HPV-16 positive women among 839 enrollees. By univariate analyses, age >25 years (OR = 3.05, 95{\%} CI 1.20-7.76), smoking (OR = 3.0, 95{\%} CI 1.19-7.56), high viral load (OR = 5.27, 95{\%} CI 2.05-13.60), detection of both E6 and E6*1 transcripts (OR = 10.0, 95{\%} CI 2.1-47.58) and high transcript copies (OR = 5.56, 95{\%} CI 2.05-13.60) were significant risk factors for CIN III with reference to No CIN/CIN I. Less than a third of the women (31.5{\%}) had prototype HPV-16 detected, and variants showed no association with disease, viral load or transcription. Viral DNA and transcript copies were highly correlated, and the ratio of transcript copies to DNA copies was not changed with disease status. While viral load, transcript copies and transcript pattern were statistically associated with CIN III, none of these measures effectively discriminated between HPV-16 women with disease requiring treatment and those who could be followed. Cellular proliferation and differentiation pathways affected by HPV should be investigated as biomarkers for cervical cancer screening.",
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Rajeevan, MS, Swan, DC, Nisenbaum, R, Lee, DR, Vernon, SD, Ruffin, MT, Horowitz, IR, Flowers, LC, Kmak, D, Tadros, T, Birdsong, G, Husain, M, Srivastava, S & Unger, ER 2005, 'Epidemiologic and viral factors associated with cervical neoplasia in HPV-16-positive women', International Journal of Cancer, vol. 115, no. 1, pp. 114-120. https://doi.org/10.1002/ijc.20894

Epidemiologic and viral factors associated with cervical neoplasia in HPV-16-positive women. / Rajeevan, Mangalathu S.; Swan, David C.; Nisenbaum, Rosane; Lee, Daisy R.; Vernon, Suzanne D.; Ruffin, Mack T.; Horowitz, Ira R.; Flowers, Lisa C.; Kmak, David; Tadros, Talaat; Birdsong, George; Husain, Mujtaba; Srivastava, Sudhir; Unger, Elizabeth R.

In: International Journal of Cancer, Vol. 115, No. 1, 20.05.2005, p. 114-120.

Research output: Contribution to journalArticle

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T1 - Epidemiologic and viral factors associated with cervical neoplasia in HPV-16-positive women

AU - Rajeevan, Mangalathu S.

AU - Swan, David C.

AU - Nisenbaum, Rosane

AU - Lee, Daisy R.

AU - Vernon, Suzanne D.

AU - Ruffin, Mack T.

AU - Horowitz, Ira R.

AU - Flowers, Lisa C.

AU - Kmak, David

AU - Tadros, Talaat

AU - Birdsong, George

AU - Husain, Mujtaba

AU - Srivastava, Sudhir

AU - Unger, Elizabeth R.

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N2 - While infection with high-risk HPV is the most important risk factor for cervical cancer, HPV alone is insufficient. Our purpose was to identify viral and epidemiologic factors associated with cervical disease in HPV-16 DNA-positive women referred to colposcopy. We used a standardized interview to collect epidemiologic data from consenting women. Total nucleic acids from exfoliated cervical cells were used for all viral assays (HPV detection and typing using L1 consensus PCR with line probe hybridization, variant classification by sequencing, viral load and transcript copy determination by quantitative PCR and transcript pattern by nested RT-PCR). Cervical disease was based on colposcopic biopsy. Logistic regression was used to calculate ORs with 95% CIs. There were 115 HPV-16 positive women among 839 enrollees. By univariate analyses, age >25 years (OR = 3.05, 95% CI 1.20-7.76), smoking (OR = 3.0, 95% CI 1.19-7.56), high viral load (OR = 5.27, 95% CI 2.05-13.60), detection of both E6 and E6*1 transcripts (OR = 10.0, 95% CI 2.1-47.58) and high transcript copies (OR = 5.56, 95% CI 2.05-13.60) were significant risk factors for CIN III with reference to No CIN/CIN I. Less than a third of the women (31.5%) had prototype HPV-16 detected, and variants showed no association with disease, viral load or transcription. Viral DNA and transcript copies were highly correlated, and the ratio of transcript copies to DNA copies was not changed with disease status. While viral load, transcript copies and transcript pattern were statistically associated with CIN III, none of these measures effectively discriminated between HPV-16 women with disease requiring treatment and those who could be followed. Cellular proliferation and differentiation pathways affected by HPV should be investigated as biomarkers for cervical cancer screening.

AB - While infection with high-risk HPV is the most important risk factor for cervical cancer, HPV alone is insufficient. Our purpose was to identify viral and epidemiologic factors associated with cervical disease in HPV-16 DNA-positive women referred to colposcopy. We used a standardized interview to collect epidemiologic data from consenting women. Total nucleic acids from exfoliated cervical cells were used for all viral assays (HPV detection and typing using L1 consensus PCR with line probe hybridization, variant classification by sequencing, viral load and transcript copy determination by quantitative PCR and transcript pattern by nested RT-PCR). Cervical disease was based on colposcopic biopsy. Logistic regression was used to calculate ORs with 95% CIs. There were 115 HPV-16 positive women among 839 enrollees. By univariate analyses, age >25 years (OR = 3.05, 95% CI 1.20-7.76), smoking (OR = 3.0, 95% CI 1.19-7.56), high viral load (OR = 5.27, 95% CI 2.05-13.60), detection of both E6 and E6*1 transcripts (OR = 10.0, 95% CI 2.1-47.58) and high transcript copies (OR = 5.56, 95% CI 2.05-13.60) were significant risk factors for CIN III with reference to No CIN/CIN I. Less than a third of the women (31.5%) had prototype HPV-16 detected, and variants showed no association with disease, viral load or transcription. Viral DNA and transcript copies were highly correlated, and the ratio of transcript copies to DNA copies was not changed with disease status. While viral load, transcript copies and transcript pattern were statistically associated with CIN III, none of these measures effectively discriminated between HPV-16 women with disease requiring treatment and those who could be followed. Cellular proliferation and differentiation pathways affected by HPV should be investigated as biomarkers for cervical cancer screening.

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