Analytic and Clinical Performance of cobas HPV Testing in Anal Specimens from HIV-Positive Men Who Have Sex with Men

Abstract

f Anal human papillomavirus (HPV) infections are common, and the incidence of anal cancer is high in HIV-infected men who have sex with men (MSM). To evaluate the performance of HPV assays in anal samples, we compared the cobas HPV test (cobas) to the Roche Linear Array HPV genotyping assay (LA) and cytology in HIV-infected MSM. Cytology and cobas and LA HPV testing were conducted for 342 subjects. We calculated agreement between the HPV assays and the clinical performance of HPV testing and HPV genotyping alone and in combination with anal cytology. We observed high agreement between cobas and LA, with cobas more likely than LA to show positive results for HPV16, HPV18, and other carcinogenic types. Specimens testing positive in cobas but not in LA were more likely to be positive for other markers of HPV-related disease compared to those testing negative in both assays, suggesting that at least some of these were true positives for HPV. cobas and LA showed high sensitivities but low specificities for the detection of anal intraepithelial neoplasia grade 2/3 (AIN2/3) in this population (100% sensitivity and 26% specificity for cobas versus 98.4% sensitivity and 28.9% specificity for LA). A combination of anal cytology and HPV genotyping provided the highest accuracy for detecting anal precancer. A higher HPV load was associated with a higher risk of AIN2/3 with HPV16 (P trend < 0.001), HPV18 (P trend ‫؍‬ 0.07), and other carcinogenic types (P trend < 0.001). We demonstrate that cobas can be used for HPV detection in anal cytology specimens. Additional tests are necessary to identify men at the highest risk of anal cancer among those infected with high-risk HPV.T he incidence of anal cancer is low in the general population but high among well-defined populations, such as women with a history of cervical precancer and men who have sex with men (MSM), particularly HIV-infected MSM, in whom the incidence is up to 80-fold higher than that in the general population (1, 2). A large proportion of anal cancer is caused by anal infections with carcinogenic human papillomavirus (HPV) (3), with approximately 80% to 85% caused by HPV16 or HPV18 (4, 5). Recent studies suggest that the epidemiology and biology of anal precancer are similar to those of cervical precancers. For example, a history of multiple anal sex partners is associated with a higher risk of anal HPV infection, and smoking is associated with an increased risk of anal precancer (6). Likewise, several well-characterized biomarkers for cervical cancer, such as HPV genotyping, HPV mRNA detection, and p16INK4a /Ki-67 immunocytochemistry, show similar clinical performance characteristics for the detection of anal precancer compared to those for cervical precancer (7).The high prevalence of anal cancer in high-risk populations, particularly HIV-infected MSM, and the similarity in natural histories between anal and cervical disease suggest that, similar to the successful cervical cancer screening model, the detection and treatment of anal precancer may prevent progre...

The Role of Human Papillomavirus Genotyping in Cervical Cancer Screening: A Large-Scale Evaluation of the cobas HPV Test

“…As expected from previous work (17), we observed that agreement between cobas and LA (at the level of HPV16, else HPV18, else 12 other HR types, else negative) was at least good in all subgroups, but tended to be stronger when viral load was higher (as indicated by HC2 positivity, abnormal cytology, or diagnosis of CIN3+ compared with controls). Also, cobas positivity for HPV16 or HPV18 was slightly higher when LA indicated the presence of a single HPV type rather than multiple HR infections.…”

Human papillomavirus status, anal cytology and histopathological outcome in HIV‐positive patients

“…Since some of our patients with normal cytology, ASCUS and LSIL had high‐grade AIN, a combination of HPV typing and cytology might be useful in detecting those patients that should be examined by HRA. In a study with 342 HIV‐positive MSM, a Californian study recently showed that a combination of anal cytology and HPV genotyping provided the highest accuracy in detecting high‐grade AIN . It may help to distinguish between those patients who are adequately screened with annual anal cytology accompanied by annual routine check‐ups and those who should be screened more closely or examined by HRA.…”

HPV infection-associated anogenital cyto-colpo-histological findings and molecular typing in HIV-positive women

“…In an analytic and clinical study, Wentzensen et al (2014) emphasized that a combination of anal cytology and HPV genotyping provided the highest accuracy for detecting anal precancer, and Cobas ® 4800 can be used for HPV detection in anal cytology specimens. In the same way, Cui et al (2014) and Agorastos et al (2015) demonstrated that HPV testing usually has a higher degree of sensitivity and specificity in detecting HR-HPV compared with cytology.…”