A comparison of human papillomavirus genotype-specific DNA and E6/E7 mRNA detection to identify anal precancer among HIV-infected men who have sex with men

Philip E. Castle, Stephen Follansbee, Sylvia Borgonovo, Diane Tokugawa, Lauren M. Schwartz, Thomas S. Lorey, Brandon LaMere, Julia C. Gage, Barbara Fetterman, Teresa M. Darragh, Ana Cecilia Rodriguez, Nicolas Wentzensen

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Abstract

Background: Human papillomavirus (HPV) RNA detection is reportedly more specific for the detection of anogenital precancer than HPV DNA but it is unknown whether this is due to detection of RNA or due to HPV genotype restriction. Methods: A total of 363 human immunodeficiency virus (HIV)-positive men who have sex with men had two anal cytology samples taken and were evaluated using high-resolution anoscopy and biopsies of visible lesions. Anal specimens were tested for E6/E7 RNA for five carcinogenic HPV genotypes (HPV16, 18, 31, 33, and 45) and tested for the DNA of 13 carcinogenic HPV genotypes. Results: DNA testing was more likely to be positive than RNA testing (53% vs. 48%; P = 0.02) for the same five HPV genotypes in aggregate. When restricted to five HPV genotypes targeted by the RNA test, the sensitivity to detect anal precancer was the same for DNA and RNA (81%), whereas RNA was more specific than DNA (65% vs. 58%; P = 0.007). In comparison, DNA detection of all 13 carcinogenic HPV genotypes was more sensitive (96% vs. 81%; P = 0.001) but much less specific (65% vs. 33%; P < 0.001) as compared with RNA detection of the five HPV genotypes. Conclusion: After controlling for HPV genotypes, RNA was only slightly more specific than DNA detection for anal precancer. Impact: DNA or RNA testing for a subset of the most carcinogenic HPV genotypes may be useful for distinguishing between those HPV-positive men at higher and lower risk of anal precancer and cancer.

Original languageEnglish (US)
Pages (from-to)42-49
Number of pages8
JournalCancer Epidemiology Biomarkers and Prevention
Volume22
Issue number1
DOIs
StatePublished - Jan 2013

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Genotype
HIV
Messenger RNA
RNA
DNA
Anus Neoplasms
Cell Biology
Biopsy

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

Cite this

A comparison of human papillomavirus genotype-specific DNA and E6/E7 mRNA detection to identify anal precancer among HIV-infected men who have sex with men. / Castle, Philip E.; Follansbee, Stephen; Borgonovo, Sylvia; Tokugawa, Diane; Schwartz, Lauren M.; Lorey, Thomas S.; LaMere, Brandon; Gage, Julia C.; Fetterman, Barbara; Darragh, Teresa M.; Rodriguez, Ana Cecilia; Wentzensen, Nicolas.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 22, No. 1, 01.2013, p. 42-49.

Research output: Contribution to journalArticle

Castle, PE, Follansbee, S, Borgonovo, S, Tokugawa, D, Schwartz, LM, Lorey, TS, LaMere, B, Gage, JC, Fetterman, B, Darragh, TM, Rodriguez, AC & Wentzensen, N 2013, 'A comparison of human papillomavirus genotype-specific DNA and E6/E7 mRNA detection to identify anal precancer among HIV-infected men who have sex with men', Cancer Epidemiology Biomarkers and Prevention, vol. 22, no. 1, pp. 42-49. https://doi.org/10.1158/1055-9965.EPI-12-0984
Castle, Philip E. ; Follansbee, Stephen ; Borgonovo, Sylvia ; Tokugawa, Diane ; Schwartz, Lauren M. ; Lorey, Thomas S. ; LaMere, Brandon ; Gage, Julia C. ; Fetterman, Barbara ; Darragh, Teresa M. ; Rodriguez, Ana Cecilia ; Wentzensen, Nicolas. / A comparison of human papillomavirus genotype-specific DNA and E6/E7 mRNA detection to identify anal precancer among HIV-infected men who have sex with men. In: Cancer Epidemiology Biomarkers and Prevention. 2013 ; Vol. 22, No. 1. pp. 42-49.
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abstract = "Background: Human papillomavirus (HPV) RNA detection is reportedly more specific for the detection of anogenital precancer than HPV DNA but it is unknown whether this is due to detection of RNA or due to HPV genotype restriction. Methods: A total of 363 human immunodeficiency virus (HIV)-positive men who have sex with men had two anal cytology samples taken and were evaluated using high-resolution anoscopy and biopsies of visible lesions. Anal specimens were tested for E6/E7 RNA for five carcinogenic HPV genotypes (HPV16, 18, 31, 33, and 45) and tested for the DNA of 13 carcinogenic HPV genotypes. Results: DNA testing was more likely to be positive than RNA testing (53{\%} vs. 48{\%}; P = 0.02) for the same five HPV genotypes in aggregate. When restricted to five HPV genotypes targeted by the RNA test, the sensitivity to detect anal precancer was the same for DNA and RNA (81{\%}), whereas RNA was more specific than DNA (65{\%} vs. 58{\%}; P = 0.007). In comparison, DNA detection of all 13 carcinogenic HPV genotypes was more sensitive (96{\%} vs. 81{\%}; P = 0.001) but much less specific (65{\%} vs. 33{\%}; P < 0.001) as compared with RNA detection of the five HPV genotypes. Conclusion: After controlling for HPV genotypes, RNA was only slightly more specific than DNA detection for anal precancer. Impact: DNA or RNA testing for a subset of the most carcinogenic HPV genotypes may be useful for distinguishing between those HPV-positive men at higher and lower risk of anal precancer and cancer.",
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AU - Tokugawa, Diane

AU - Schwartz, Lauren M.

AU - Lorey, Thomas S.

AU - LaMere, Brandon

AU - Gage, Julia C.

AU - Fetterman, Barbara

AU - Darragh, Teresa M.

AU - Rodriguez, Ana Cecilia

AU - Wentzensen, Nicolas

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N2 - Background: Human papillomavirus (HPV) RNA detection is reportedly more specific for the detection of anogenital precancer than HPV DNA but it is unknown whether this is due to detection of RNA or due to HPV genotype restriction. Methods: A total of 363 human immunodeficiency virus (HIV)-positive men who have sex with men had two anal cytology samples taken and were evaluated using high-resolution anoscopy and biopsies of visible lesions. Anal specimens were tested for E6/E7 RNA for five carcinogenic HPV genotypes (HPV16, 18, 31, 33, and 45) and tested for the DNA of 13 carcinogenic HPV genotypes. Results: DNA testing was more likely to be positive than RNA testing (53% vs. 48%; P = 0.02) for the same five HPV genotypes in aggregate. When restricted to five HPV genotypes targeted by the RNA test, the sensitivity to detect anal precancer was the same for DNA and RNA (81%), whereas RNA was more specific than DNA (65% vs. 58%; P = 0.007). In comparison, DNA detection of all 13 carcinogenic HPV genotypes was more sensitive (96% vs. 81%; P = 0.001) but much less specific (65% vs. 33%; P < 0.001) as compared with RNA detection of the five HPV genotypes. Conclusion: After controlling for HPV genotypes, RNA was only slightly more specific than DNA detection for anal precancer. Impact: DNA or RNA testing for a subset of the most carcinogenic HPV genotypes may be useful for distinguishing between those HPV-positive men at higher and lower risk of anal precancer and cancer.

AB - Background: Human papillomavirus (HPV) RNA detection is reportedly more specific for the detection of anogenital precancer than HPV DNA but it is unknown whether this is due to detection of RNA or due to HPV genotype restriction. Methods: A total of 363 human immunodeficiency virus (HIV)-positive men who have sex with men had two anal cytology samples taken and were evaluated using high-resolution anoscopy and biopsies of visible lesions. Anal specimens were tested for E6/E7 RNA for five carcinogenic HPV genotypes (HPV16, 18, 31, 33, and 45) and tested for the DNA of 13 carcinogenic HPV genotypes. Results: DNA testing was more likely to be positive than RNA testing (53% vs. 48%; P = 0.02) for the same five HPV genotypes in aggregate. When restricted to five HPV genotypes targeted by the RNA test, the sensitivity to detect anal precancer was the same for DNA and RNA (81%), whereas RNA was more specific than DNA (65% vs. 58%; P = 0.007). In comparison, DNA detection of all 13 carcinogenic HPV genotypes was more sensitive (96% vs. 81%; P = 0.001) but much less specific (65% vs. 33%; P < 0.001) as compared with RNA detection of the five HPV genotypes. Conclusion: After controlling for HPV genotypes, RNA was only slightly more specific than DNA detection for anal precancer. Impact: DNA or RNA testing for a subset of the most carcinogenic HPV genotypes may be useful for distinguishing between those HPV-positive men at higher and lower risk of anal precancer and cancer.

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