Human papillomavirus genotyping, human papillomavirus mRNA expression, and p16/Ki-67 cytology to detect anal cancer precursors in HIV-infected MSM

Nicolas Wentzensen, Stephen Follansbee, Sylvia Borgonovo, Diane Tokugawa, Lauren Schwartz, Thomas S. Lorey, Vikrant V. Sahasrabuddhe, Brandon Lamere, Julia C. Gage, Barbara Fetterman, Teresa M. Darragh, Philip E. Castle

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

OBJECTIVE: Anal cancer incidence is high in HIV-infected MSM. Screening for anal intraepithelial lesions and cancers is performed at specialized clinics and relies on high-resolution anoscopy (HRA) and anal cytology. Both approaches have limited reproducibility and sensitivity for detecting anal cancer precursors. We evaluated biomarkers for human papillomavirus (HPV)-related disease in a population of HIV-infected MSM. METHODS: A cross-sectional screening study with passive follow-up included 363 MSM followed at a HIV/AIDS clinic. All men had anal cytology samples taken and were evaluated using HRA and anal biopsies. Using a composite endpoint of biopsy results and cytology, we compared the performance of HPV16/18 genotyping, HPVE6/E7 mRNA expression, and p16/Ki-67 cytology to detect high-grade anal intraepithelial neoplasias (AINs). RESULTS: For all biomarkers analyzed, there was a significant trend of increasing percentage of men testing positive with increasing severity of disease (P<0.001). HPV DNA testing had the highest sensitivity for anal intraepithelial neoplasia grade 2 and anal intraepithelial neoplasia grade 3 (AIN3), followed by p16/Ki-67, HPVE6/E7 mRNA testing, and HPV16/18 genotyping. The highest Youden's index was observed for HPVE6/E7 mRNA testing, followed by HPV16/18 genotyping, p16/Ki-67 cytology, and HPV DNA testing. Increasing the threshold for positivity of p16/Ki-67 to five or more positive cells led to significantly higher specificity, but unchanged sensitivity for detecting AIN3. CONCLUSION: Molecular features of anal disease categories are similar to those of corresponding cervical lesions. Biomarkers evaluated for cervical cancer screening may be used for primary anal cancer screening or to decide who should require immediate treatment vs. expectant management.

Original languageEnglish (US)
Pages (from-to)2185-2192
Number of pages8
JournalAIDS
Volume26
Issue number17
DOIs
StatePublished - Nov 13 2012
Externally publishedYes

Fingerprint

Anus Neoplasms
Cell Biology
HIV
Messenger RNA
Biomarkers
Neoplasms
Early Detection of Cancer
Biopsy
DNA
Uterine Cervical Neoplasms
Acquired Immunodeficiency Syndrome
Cross-Sectional Studies
Sensitivity and Specificity
Incidence
Population

Keywords

  • anal cancer screening
  • HIV
  • human papillomavirus
  • human papillomavirus mRNA
  • MSM
  • p16

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

Human papillomavirus genotyping, human papillomavirus mRNA expression, and p16/Ki-67 cytology to detect anal cancer precursors in HIV-infected MSM. / Wentzensen, Nicolas; Follansbee, Stephen; Borgonovo, Sylvia; Tokugawa, Diane; Schwartz, Lauren; Lorey, Thomas S.; Sahasrabuddhe, Vikrant V.; Lamere, Brandon; Gage, Julia C.; Fetterman, Barbara; Darragh, Teresa M.; Castle, Philip E.

In: AIDS, Vol. 26, No. 17, 13.11.2012, p. 2185-2192.

Research output: Contribution to journalArticle

Wentzensen, N, Follansbee, S, Borgonovo, S, Tokugawa, D, Schwartz, L, Lorey, TS, Sahasrabuddhe, VV, Lamere, B, Gage, JC, Fetterman, B, Darragh, TM & Castle, PE 2012, 'Human papillomavirus genotyping, human papillomavirus mRNA expression, and p16/Ki-67 cytology to detect anal cancer precursors in HIV-infected MSM', AIDS, vol. 26, no. 17, pp. 2185-2192. https://doi.org/10.1097/QAD.0b013e328359f255
Wentzensen, Nicolas ; Follansbee, Stephen ; Borgonovo, Sylvia ; Tokugawa, Diane ; Schwartz, Lauren ; Lorey, Thomas S. ; Sahasrabuddhe, Vikrant V. ; Lamere, Brandon ; Gage, Julia C. ; Fetterman, Barbara ; Darragh, Teresa M. ; Castle, Philip E. / Human papillomavirus genotyping, human papillomavirus mRNA expression, and p16/Ki-67 cytology to detect anal cancer precursors in HIV-infected MSM. In: AIDS. 2012 ; Vol. 26, No. 17. pp. 2185-2192.
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abstract = "OBJECTIVE: Anal cancer incidence is high in HIV-infected MSM. Screening for anal intraepithelial lesions and cancers is performed at specialized clinics and relies on high-resolution anoscopy (HRA) and anal cytology. Both approaches have limited reproducibility and sensitivity for detecting anal cancer precursors. We evaluated biomarkers for human papillomavirus (HPV)-related disease in a population of HIV-infected MSM. METHODS: A cross-sectional screening study with passive follow-up included 363 MSM followed at a HIV/AIDS clinic. All men had anal cytology samples taken and were evaluated using HRA and anal biopsies. Using a composite endpoint of biopsy results and cytology, we compared the performance of HPV16/18 genotyping, HPVE6/E7 mRNA expression, and p16/Ki-67 cytology to detect high-grade anal intraepithelial neoplasias (AINs). RESULTS: For all biomarkers analyzed, there was a significant trend of increasing percentage of men testing positive with increasing severity of disease (P<0.001). HPV DNA testing had the highest sensitivity for anal intraepithelial neoplasia grade 2 and anal intraepithelial neoplasia grade 3 (AIN3), followed by p16/Ki-67, HPVE6/E7 mRNA testing, and HPV16/18 genotyping. The highest Youden's index was observed for HPVE6/E7 mRNA testing, followed by HPV16/18 genotyping, p16/Ki-67 cytology, and HPV DNA testing. Increasing the threshold for positivity of p16/Ki-67 to five or more positive cells led to significantly higher specificity, but unchanged sensitivity for detecting AIN3. CONCLUSION: Molecular features of anal disease categories are similar to those of corresponding cervical lesions. Biomarkers evaluated for cervical cancer screening may be used for primary anal cancer screening or to decide who should require immediate treatment vs. expectant management.",
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AU - Tokugawa, Diane

AU - Schwartz, Lauren

AU - Lorey, Thomas S.

AU - Sahasrabuddhe, Vikrant V.

AU - Lamere, Brandon

AU - Gage, Julia C.

AU - Fetterman, Barbara

AU - Darragh, Teresa M.

AU - Castle, Philip E.

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