(602) Adult-Onset Head and Neck Cancer in Germline TP53 Carriers: A Retrospective Cohort Analysis

Introduction: Acquired TP53 mutations play a central role in sporadic head and neck squamous cell carcinoma (HNSCC). Li Fraumeni Syndrome (LFS), an inherited cancer predisposition syndrome, is caused by TP53 pathogenic germline variants (PGV). While the theoretical risk of HNSCC in LFS patients has been discussed, HNSCC in adult LFS patients is not well described in the literature. We report on prevalence, incidence, and characteristics of all non-thyroid head and neck cancers in an adult LFS cohort.

Methods: We conducted a retrospective cohort study of head and neck cancer in 241 adult patients with LFS at Penn Medicine. Cancers were identified by chart review; tumor site, histopathology, risk factors, and outcomes abstracted. HNSCC incidence was estimated using person-time from age 18 until first HNSCC diagnosis, death, or last follow-up.

Results: Among 241 adult LFS patients, head and neck cancer occurred in six patients (2.49%) at a median age of 54.5 years (IQR 39-66). Patients with H&N cancer were all Caucasian, 50% female, and with evenly distributed TP53 PGV subtypes. HNSCC occurred in three patients (1.2%), with tumors in the tonsil, lateral tongue, and tongue base. All HNSCC occurred in the absence of prior head and neck radiation or tobacco use. One tumor was p16 positive. Estimated incidence of oral cavity and pharynx cancer in our LFS cohort (0.05%) is higher than SEER age-adjusted incidence rates for males (0.016-0.018%) and females (0.006-0.007%) from 2000-2022. The remaining three H&N tumors identified were sarcomas – a cervical soft tissue spindle cell sarcoma in the radiation field of a prior breast cancer, a primary mandibular osteosarcoma, and a primary mandibular chondrosarcoma.

Conclusions: HNSCC remains rare in LFS, but our findings suggest a possible increased risk independent of several traditional risk factors. Although this cohort is small, these observations add to the limited evidence base exploring a potential relationship between TP53 germline mutations and HNSCC. Ongoing expansion of this cohort will enable more reliable standardized incidence ratio estimates to further clarify this association