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



Baseline analysis of a 3-year cohort study.



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 p16/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.



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).



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.
aThe Kirby Institute, University of New South Wales bDouglass Hanly Moir Pathology, Sydney, New South Wales cRoyal Women's Hospital, University of Melbourne, Murdoch Childrens Research Institute, Melbourne, Victoria dWestern Sydney Sexual Health Centre, University of Sydney eSt Vincent's Hospital, Sydney, New South Wales fRPA Sexual Health, Sydney Local Health District and Central Clinical School, University of Sydney, Sydney, New South Wales gMelbourne Sexual Health Centre, Melbourne, Victoria, Australia.
Fengyi
F
Jin
Jennifer M
JM
Roberts
Andrew E
AE
Grulich
Isobel M
IM
Poynten
Dorothy A
DA
Machalek
Alyssa
A
Cornall
Samuel
S
Phillips
Deborah
D
Ekman
Ross L
RL
McDonald
Richard J
RJ
Hillman
David J
DJ
Templeton
Annabelle
A
Farnsworth
Suzanne M
SM
Garland
Christopher K
CK
Fairley
Sepehr N
SN
Tabrizi
D000328:Adult; D000368:Aged; D001005:Anus Neoplasms / Q000175:diagnosis*; D001315:Australia; D014408:Biomarkers, Tumor / Q000032:analysis*; D015331:Cohort Studies; D004279:DNA, Viral / Q000032:analysis*; D003955:Diagnostic Tests, Routine / Q000379:methods; D005260:Female; D005838:Genotype; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D027383:Papillomaviridae / Q000235:genetics / Q000302:isolation & purification*; D012367:RNA, Viral / Q000032:analysis*; D012680:Sensitivity and Specificity; D000072339:Sexual and Gender Minorities; D065310:Squamous Intraepithelial Lesions of the Cervix / Q000175:diagnosis*; D019562:Viral Load
D014408:Biomarkers, Tumor; D004279:DNA, Viral; D012367:RNA, Viral