Introduction: Histopathologic assessment of surgical specimens imparts crucial information that is essential for diagnosis, treatment planning and prognostication for patients with Oropharyngeal Squamous Cell Carcinoma (OPSCC). This review explores the range of diagnostic techniques utilized to assess the HPV (Human Papilloma Virus) status in OPSCC. It covers both traditional methods—such as p16 immunohistochemistry, HPV in situ hybridization, and DNA polymerase chain reaction (PCR)—and newer, evolving strategies including circulating HPV tumor DNA analysis and oral HPV DNA/mRNA PCR testing. Discussion: There are currently several histopathologic techniques for the diagnosis of HPV-associated OPSCC. This complexity of care has led to guidelines from numerous authorities (NCCN, ASCO, CAP), which this paper discusses and summarizes for head and neck oncology specialists. Conclusion: The ability to detect HPV in HPV-associated OPSCC is imperative for diagnosis, prognostication, staging, and management of the disease. Advances including liquid biopsy (TTMV-HPV DNA) may be utilized as an adjunct to diagnosis, treatment, and cancer surveillance in the future.

MRE11, a breast tumor suppressor and component of the MRE11-RAD50-NBS1 (MRN) complex, plays a critical role in DNA end resection and initiation of ATM-dependent DNA damage signaling. However, the precise mechanisms governing MRE11 function in the DNA damage response (DDR) remain incompletely understood. Here, we found that MRE11 is deacetylated by the SIRT2 sirtuin deacetylase and breast tumor suppressor, which promotes DNA binding to facilitate DNA end resection and ATM-dependent signaling. SIRT2 deacetylase activity promoted DNA end resection. SIRT2 further complexed with and deacetylated MRE11 at conserved lysine (K) 393 in response to DNA double-strand breaks (DSBs), which promoted MRE11 localization and DNA binding at DSBs but not interaction with RAD50, NBS1, or CtIP. Moreover, MRE11 K393 deacetylation by SIRT2 promoted ATM-dependent signaling. Our findings define a mechanism regulating MRE11 binding to DNA through SIRT2 deacetylation, elucidating a critical upstream signaling event directing MRE11 function in the DDR and providing insight into how SIRT2 dysregulation leads to genomic instability and tumorigenesis.