Significance of non16/non18 high-risk HPV in women with negative or atypical concomitant cervical cytology
Hogan K, Zhang Z, Schultz D, Gaba A, and Allo G. Significance of non16/non18 high-risk HPV in women with negative or atypical concomitant cervical cytology. Lab Invest 2018; 98:149.
Background: Human papilloma virus (HPV) testing on cervical samples is being introduced as a standalone screening test. Clinical algorithm focuses on management of patients with the most common HPV types, 16 and 18. We aim in this study to examine the clinical significance of finding other high-risk HPV types on cervical samples that are cytologically negative or show only atypical squamous cells of unknown significance (ASC-US). Design: We retrospectively analysed patients who underwent cervical cytology and HPV co-testing at our institution in 2013. HPV testing was conducted using FDA-approved Cobas HPV Test (Roche Diagnostics), classifying HPV into HPV16, HPV18, and pooled non16/non18 HPV (types 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68). Cases with no previous abnormal cytology or HPV were included, and were classified based on HPV test into negative, non16/non18 HPV, and HPV16/18. Results of subsequent pathology are recorded, specifically high grade squamous intraepithelial lesion (HSIL) or carcinoma, categorized in this study under HSIL. Descriptive analysis and Pearson Chi-square test were conducted. Results: A total of 4075 cases were analyzed, with mean age of 43yrs (17-95). These include 2166(53%) negative and 1637(40%) ASC-US cytology. Overall, non16/non18 HPV was detected in 309(8%) cases, and HPV16/18 in 105(3%) cases. Among patients with negative cytology, non16/non18 HPV and HPV16/18 were found in 64(3%) and 17(0.8%) cases, respectively. The risk of HSIL development in cases with non16/non18 HPV is not different from that of HPV16/18(p=0.6), but is higher than that of HPV negative cases(p<0.0001). These findings are similar in patients older than 29yrs. Among patients with ASC-US cytology, non16/non18 HPV was detected in 158(10%) cases while HPV16/18 in 56(3%) cases. The risk of HSIL in cases with non16/non18 HPV is higher than that of negative HPV cases(p<0.0001) but lower than that of HPV16/18(p=0.036). In patients older than 29yrs, HSIL development risk is not different between non16/non18 HPV and HPV16/18(p=0.37), but is higher than that of HPV negative cases (p<0.0001). Conclusions: For patients who developed HSIL after proceeding negative cytology, or in those >29yrs with ASC-US cytology, the prevalence of non16/non18 HPV is not different from HPV16/HPV18. This study argues against stratification of high-risk HPV into different types (HPV16/18 vs non16/non18 HPV).