TY - JOUR
T1 - Human papillomavirus genotyping, human papillomavirus mRNA expression, and p16/Ki-67 cytology to detect anal cancer precursors in HIV-infected MSM
AU - Wentzensen, Nicolas
AU - Follansbee, Stephen
AU - Borgonovo, Sylvia
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.
PY - 2012/11/13
Y1 - 2012/11/13
N2 - 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.
AB - 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.
KW - HIV
KW - MSM
KW - anal cancer screening
KW - human papillomavirus
KW - human papillomavirus mRNA
KW - p16
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UR - http://www.scopus.com/inward/citedby.url?scp=84869505733&partnerID=8YFLogxK
U2 - 10.1097/QAD.0b013e328359f255
DO - 10.1097/QAD.0b013e328359f255
M3 - Article
C2 - 23018436
AN - SCOPUS:84869505733
SN - 0269-9370
VL - 26
SP - 2185
EP - 2192
JO - AIDS
JF - AIDS
IS - 17
ER -