The performance of human papillomavirus biomarkers in predicting anal high-grade squamous intraepithelial lesions in gay and bisexual men

Fengyi Jin, Jennifer M. Roberts, Andrew E Grulich, Isobel Mary Poynten, Dorothy A Machalek, Alyssa Cornall, Samuel Phillips, Deborah L Ekman, Ross Lindsay McDonald, Richard J Hillman, David J Templeton, Annabelle Farnsworth, Christopher K. Fairley, Sepehr N Tabrizi, on behalf of the SPANC Research Team

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Background: We evaluate the performance of human papillomavirus (HPV) biomarkers in prediction of anal histological high-grade squamous intraepithelial lesions in gay and bisexual men (GBM) in Sydney, Australia. Design: Baseline analysis of a 3-year cohort study. Methods: The Study of the Prevention of Anal Cancer is natural history study of anal HPV infection in GBM aged at least 35 years. All participants completed cytological and histological assessments. Stored ThinPrep PreservCyt residua were tested for HPV genotyping (Linear Array and Cobas 4800) and viral load, E6/E7 mRNA expression (NucliSENS easyQ HPV v1) and dual cytology staining of p16INK4a/Ki 67 antibodies (CINtecPLUS). Performance of each biomarker was compared with liquid-based anal cytology. The hypothetical referral rates were defined as the proportion of men who had abnormal cytology or tested positive to each of the biomarkers. Results: The median age of the 617 participants was 49 years (range: 35-79), and 35.7% were HIV-positive. All biomarkers were strongly associated with the grade of HPV-associated anal lesions (P < 0.001 for all). High-risk HPV (HR-HPV) viral load with a 33% cut-off and HR-HPV E6/E7 mRNA had similar sensitivity to anal cytology (78.4 and 75.4 vs. 83.2%, respectively), improved specificity (68.0 and 69.4 vs. 52.4%, respectively) and lower referral rates (47.0 and 45.0 vs. 59.2%, respectively). Specificity was significantly higher in the HIV-negative for HR-HPV viral load (72.3 vs. 58.2%, P = 0.005). Conclusion: HR-HPV viral load and E6/E7 mRNA had similar sensitivity and higher specificity in predicting histological anal high-grade squamous intraepithelial lesion with lower referrals in GBM than anal cytology.

Original languageEnglish
Pages (from-to)1303-1311
Number of pages9
JournalAIDS
Volume31
Issue number9
DOIs
Publication statusPublished - 1 Jun 2017

Keywords

  • anal cancer
  • biomarker
  • cancer screening
  • homosexuality
  • human papillomavirus
  • male

Cite this

Jin, F., Roberts, J. M., Grulich, A. E., Poynten, I. M., Machalek, D. A., Cornall, A., ... on behalf of the SPANC Research Team (2017). The performance of human papillomavirus biomarkers in predicting anal high-grade squamous intraepithelial lesions in gay and bisexual men. AIDS, 31(9), 1303-1311. https://doi.org/10.1097/QAD.0000000000001462
Jin, Fengyi ; Roberts, Jennifer M. ; Grulich, Andrew E ; Poynten, Isobel Mary ; Machalek, Dorothy A ; Cornall, Alyssa ; Phillips, Samuel ; Ekman, Deborah L ; McDonald, Ross Lindsay ; Hillman, Richard J ; Templeton, David J ; Farnsworth, Annabelle ; Fairley, Christopher K. ; Tabrizi, Sepehr N ; on behalf of the SPANC Research Team. / The performance of human papillomavirus biomarkers in predicting anal high-grade squamous intraepithelial lesions in gay and bisexual men. In: AIDS. 2017 ; Vol. 31, No. 9. pp. 1303-1311.
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title = "The performance of human papillomavirus biomarkers in predicting anal high-grade squamous intraepithelial lesions in gay and bisexual men",
abstract = "Background: We evaluate the performance of human papillomavirus (HPV) biomarkers in prediction of anal histological high-grade squamous intraepithelial lesions in gay and bisexual men (GBM) in Sydney, Australia. Design: Baseline analysis of a 3-year cohort study. Methods: The Study of the Prevention of Anal Cancer is natural history study of anal HPV infection in GBM aged at least 35 years. All participants completed cytological and histological assessments. Stored ThinPrep PreservCyt residua were tested for HPV genotyping (Linear Array and Cobas 4800) and viral load, E6/E7 mRNA expression (NucliSENS easyQ HPV v1) and dual cytology staining of p16INK4a/Ki 67 antibodies (CINtecPLUS). Performance of each biomarker was compared with liquid-based anal cytology. The hypothetical referral rates were defined as the proportion of men who had abnormal cytology or tested positive to each of the biomarkers. Results: The median age of the 617 participants was 49 years (range: 35-79), and 35.7{\%} were HIV-positive. All biomarkers were strongly associated with the grade of HPV-associated anal lesions (P < 0.001 for all). High-risk HPV (HR-HPV) viral load with a 33{\%} cut-off and HR-HPV E6/E7 mRNA had similar sensitivity to anal cytology (78.4 and 75.4 vs. 83.2{\%}, respectively), improved specificity (68.0 and 69.4 vs. 52.4{\%}, respectively) and lower referral rates (47.0 and 45.0 vs. 59.2{\%}, respectively). Specificity was significantly higher in the HIV-negative for HR-HPV viral load (72.3 vs. 58.2{\%}, P = 0.005). Conclusion: HR-HPV viral load and E6/E7 mRNA had similar sensitivity and higher specificity in predicting histological anal high-grade squamous intraepithelial lesion with lower referrals in GBM than anal cytology.",
keywords = "anal cancer, biomarker, cancer screening, homosexuality, human papillomavirus, male",
author = "Fengyi Jin and Roberts, {Jennifer M.} and Grulich, {Andrew E} and Poynten, {Isobel Mary} and Machalek, {Dorothy A} and Alyssa Cornall and Samuel Phillips and Ekman, {Deborah L} and McDonald, {Ross Lindsay} and Hillman, {Richard J} and Templeton, {David J} and Annabelle Farnsworth and Fairley, {Christopher K.} and Tabrizi, {Sepehr N} and {on behalf of the SPANC Research Team}",
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Jin, F, Roberts, JM, Grulich, AE, Poynten, IM, Machalek, DA, Cornall, A, Phillips, S, Ekman, DL, McDonald, RL, Hillman, RJ, Templeton, DJ, Farnsworth, A, Fairley, CK, Tabrizi, SN & on behalf of the SPANC Research Team 2017, 'The performance of human papillomavirus biomarkers in predicting anal high-grade squamous intraepithelial lesions in gay and bisexual men' AIDS, vol. 31, no. 9, pp. 1303-1311. https://doi.org/10.1097/QAD.0000000000001462

The performance of human papillomavirus biomarkers in predicting anal high-grade squamous intraepithelial lesions in gay and bisexual men. / Jin, Fengyi; Roberts, Jennifer M.; Grulich, Andrew E; Poynten, Isobel Mary; Machalek, Dorothy A; Cornall, Alyssa; Phillips, Samuel; Ekman, Deborah L; McDonald, Ross Lindsay; Hillman, Richard J; Templeton, David J; Farnsworth, Annabelle; Fairley, Christopher K.; Tabrizi, Sepehr N; on behalf of the SPANC Research Team.

In: AIDS, Vol. 31, No. 9, 01.06.2017, p. 1303-1311.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - The performance of human papillomavirus biomarkers in predicting anal high-grade squamous intraepithelial lesions in gay and bisexual men

AU - Jin, Fengyi

AU - Roberts, Jennifer M.

AU - Grulich, Andrew E

AU - Poynten, Isobel Mary

AU - Machalek, Dorothy A

AU - Cornall, Alyssa

AU - Phillips, Samuel

AU - Ekman, Deborah L

AU - McDonald, Ross Lindsay

AU - Hillman, Richard J

AU - Templeton, David J

AU - Farnsworth, Annabelle

AU - Fairley, Christopher K.

AU - Tabrizi, Sepehr N

AU - on behalf of the SPANC Research Team

PY - 2017/6/1

Y1 - 2017/6/1

N2 - Background: We evaluate the performance of human papillomavirus (HPV) biomarkers in prediction of anal histological high-grade squamous intraepithelial lesions in gay and bisexual men (GBM) in Sydney, Australia. Design: Baseline analysis of a 3-year cohort study. Methods: The Study of the Prevention of Anal Cancer is natural history study of anal HPV infection in GBM aged at least 35 years. All participants completed cytological and histological assessments. Stored ThinPrep PreservCyt residua were tested for HPV genotyping (Linear Array and Cobas 4800) and viral load, E6/E7 mRNA expression (NucliSENS easyQ HPV v1) and dual cytology staining of p16INK4a/Ki 67 antibodies (CINtecPLUS). Performance of each biomarker was compared with liquid-based anal cytology. The hypothetical referral rates were defined as the proportion of men who had abnormal cytology or tested positive to each of the biomarkers. Results: The median age of the 617 participants was 49 years (range: 35-79), and 35.7% were HIV-positive. All biomarkers were strongly associated with the grade of HPV-associated anal lesions (P < 0.001 for all). High-risk HPV (HR-HPV) viral load with a 33% cut-off and HR-HPV E6/E7 mRNA had similar sensitivity to anal cytology (78.4 and 75.4 vs. 83.2%, respectively), improved specificity (68.0 and 69.4 vs. 52.4%, respectively) and lower referral rates (47.0 and 45.0 vs. 59.2%, respectively). Specificity was significantly higher in the HIV-negative for HR-HPV viral load (72.3 vs. 58.2%, P = 0.005). Conclusion: HR-HPV viral load and E6/E7 mRNA had similar sensitivity and higher specificity in predicting histological anal high-grade squamous intraepithelial lesion with lower referrals in GBM than anal cytology.

AB - Background: We evaluate the performance of human papillomavirus (HPV) biomarkers in prediction of anal histological high-grade squamous intraepithelial lesions in gay and bisexual men (GBM) in Sydney, Australia. Design: Baseline analysis of a 3-year cohort study. Methods: The Study of the Prevention of Anal Cancer is natural history study of anal HPV infection in GBM aged at least 35 years. All participants completed cytological and histological assessments. Stored ThinPrep PreservCyt residua were tested for HPV genotyping (Linear Array and Cobas 4800) and viral load, E6/E7 mRNA expression (NucliSENS easyQ HPV v1) and dual cytology staining of p16INK4a/Ki 67 antibodies (CINtecPLUS). Performance of each biomarker was compared with liquid-based anal cytology. The hypothetical referral rates were defined as the proportion of men who had abnormal cytology or tested positive to each of the biomarkers. Results: The median age of the 617 participants was 49 years (range: 35-79), and 35.7% were HIV-positive. All biomarkers were strongly associated with the grade of HPV-associated anal lesions (P < 0.001 for all). High-risk HPV (HR-HPV) viral load with a 33% cut-off and HR-HPV E6/E7 mRNA had similar sensitivity to anal cytology (78.4 and 75.4 vs. 83.2%, respectively), improved specificity (68.0 and 69.4 vs. 52.4%, respectively) and lower referral rates (47.0 and 45.0 vs. 59.2%, respectively). Specificity was significantly higher in the HIV-negative for HR-HPV viral load (72.3 vs. 58.2%, P = 0.005). Conclusion: HR-HPV viral load and E6/E7 mRNA had similar sensitivity and higher specificity in predicting histological anal high-grade squamous intraepithelial lesion with lower referrals in GBM than anal cytology.

KW - anal cancer

KW - biomarker

KW - cancer screening

KW - homosexuality

KW - human papillomavirus

KW - male

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DO - 10.1097/QAD.0000000000001462

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