The DNA deaminase AID initiates somatic hypermutation (SHM) and class switch recombination (CSR) by deaminating cytidines to uridines at variable region (V) genes and switch (S) regions. The mechanism by which AID is recruited to V genes and S region DNA is poorly understood. Here we have employed the CH12 B lymphoma line to demonstrate that while S regions can efficiently recruit AID and undergo mutations and deletions, AID neither binds to nor mutates the V gene, thus clearly demonstrating intra-immunoglobulin locus specificity. Depletion of the RNA-binding protein Ptpb2, previously shown to promote recruitment of AID to S regions, enables stable association of AID with the V gene. Surprisingly, AID binding to the V gene does not induce SHM. These results unmask a striking lack of correlation between AID binding and its mutator activity, providing evidence for the presence of factors required downstream of AID binding to effect SHM. Furthermore, our findings suggest that S regions are preferred targets for AID and, aided by Ptbp2, act as “sinks” to sequester AID activity from other genomic regions.

Background Human papilloma virus testing for oropharyngeal squamous‐cell carcinoma has been recommended by the National Comprehensive Cancer Network since 2012. We examine disparities, reported rates of human papillomavirus (HPV) testing, and the impact on these findings of limitations with the variable in database registries. Methods The HPV variable was queried for patients with oropharyngeal squamous carcinoma (OPSCC) from 2013 to 2016 in National Cancer Data Base (NCDB) and Surveillance, Epidemiology, and End Results (SEER). Multivariable regression was used to identify disparities based on sociodemographic variables. Sensitivity analyses were used to investigate limitations of the variable. Results Despite limitations in the HPV variable in the databases, there was less than 100% adherence to recommended testing, and there were significant disparities in multiple sociodemographic variables. For example, in NCDB 70% of white versus 60.4% of black patients were tested (odds ratio [OR] 0.75, confidence interval [CI] 0.66–0.85, p ≤ 0.0001); in SEER 59.8% of white and 47.6% of black patients were tested (OR 0.73, CI 0.67–0.81; p ≤ 0.0001). Conclusions Disparities exist among patients undergoing testing for HPV‐associated OPSCC and adherence to guideline recommended HPV testing has been suboptimal. In addition, the HPV variable definition, especially as it relates to p16 positivity, and use in these two registries should be improved.