Purpose: Current classification of head and neck squamous cell carcinomas (HNSCC) based on anatomic site and stage fails to capture biologic heterogeneity or adequately inform treatment.Experimental

Although xerostomia is a commonly reported complaint in patients with chronic graft versus host disease (cGVHD), criteria for evaluating the prevalence and characteristics of salivary gland involvement have not been well defined in this patient population. Prior studies also do not make distinction between salivary and mucosal oral cGVHD. We have systematically evaluated sicca symptoms and signs in a large cohort of patients with cGVHD (N=101) using instruments widely used to study Sjogren’s Syndrome. Xerostomia was reported by 77% of the patients and was associated with xerophthalmia in all cases but one. Twenty-seven percent had salivary flow rates of ≤0.2 ml/min, 16% had rates ≤0.1 ml/min. Histopathological changes consisting of mononuclear infiltration and/or fibrosis/atrophy, were present in all patients with salivary dysfunction. Importantly, there was no correlation of salivary and oral mucosal involvement in cGVHD. Patients with cGVHD-associated salivary gland involvement had lower oral cavity-specific quality of life and body mass index. In conclusion, salivary gland involvement is a common and clinically distinct manifestation of cGVHD. Formal evaluation of salivary function using standardized criteria is necessary and may be incorporated as outcome measure in clinical trials of cGVHD.

Although chronic graft-versus-host disease (cGVHD) is a major long-term complication of allogeneic hematopoietic stem cell transplantation, little is known of its pathogenesis. We have systematically examined oral mucosa among cGVHD patients and determined that the clinical severity of oral cGVHD was correlated with apoptotic epithelial cells, often found adjacent to infiltrating effector-memory T cells expressing markers of cytotoxicity and type I cytokine polarization. Accumulation of T-bet ؉ T-cell effectors was asso-