HPV+ OPC has a different biology compared with HPV- OPC; 5-year OS, PFS, and local-regional control are unprecedented. These results support the possibility of selectively reducing therapy and long-term morbidity in HPV+ OPC while preserving survival and approaching HPV- disease with more aggressive treatment.

The burden of squamous cell carcinoma of the head and neck (SCCHN) is greater for blacks than for whites, especially in oropharyngeal cases. We previously showed retrospectively that disease-free survival was significantly greater in white than in black SCCHN patients treated with chemoradiation, the greatest difference occurring in the oropharyngeal subgroup. Oropharyngeal cancer is increasing in incidence and in its association with human papillomavirus (HPV) infection; HPV-positive oropharyngeal cancer patients have significantly better outcomes (versus HPV-negative). These collective data led to the present analyses of overall survival (OS) in our retrospective cohort and of OS and HPV status (tested prospectively in pretreatment biopsy specimens) in the phase 3, multicenter TAX 324 trial of induction chemotherapy followed by concurrent chemoradiation in SCCHN patients. Median OS in the retrospective cohort of 106 white and 95 black SCCHN patients was 52.1 months (white) versus only 23.7 months (black; P = 0.009), due entirely to OS in the subgroup of patients with oropharyngeal cancer—69.4 months (whites) versus 25.2 months (blacks; P = 0.0006); no significant difference by race occurred in survival of non-oropharyngeal SCCHN (P = 0.58). In TAX 324, 196 white patients and 28 black patients could be assessed for HPV status. Median OS was significantly worse for black patients (20.9 months) than for white patients (70.6 months; P = 0.03) and dramatically improved in HPV-positive (not reached) versus HPV-negative (26.6 months, 5.1 hazard ratio) oropharyngeal patients (P < 0.0001), 49% of whom were HPV-16 positive. Overall, HPV positivity was 34% in white versus 4% in black patients (P = 0.0004). Survival was similar for black and white HPV-negative patients (P = 0.56). This is the first prospective assessment of confirmed HPV status in black versus white SCCHN patients. Worse OS for black SCCHN patients was driven by oropharyngeal cancer outcomes, and that for black oropharyngeal cancer patients by a lower prevalence of HPV infection. These findings have important implications for the etiology, prevention, prognosis, and treatment of SCCHN.

Purpose: Cisplatin adducts to nuclear DNA (nDNA) are felt to be the molecular lesions that trigger apoptosis, but the mechanism linking nDNA adduct formation and cell death is unclear. Some literature in the last decade has suggested a possible direct effect of cisplatin on mitochondria independent of nDNA interaction. In this study, we define separately the sequelae of cisplatin interactions with nDNA and with mitochondria in head and neck squamous cell carcinoma (HNSCC) cell lines. Experimental Design: Cisplatin binding to mitochondrial DNA (mtDNA) and proteins was analyzed by atomic absorption spectroscopy and other methods.

Background Racial outcome disparities have been observed in HNSCC with diminished survival for black patients compared to whites. Methods We retrospectively analyzed 1318 patients with primary HNSCC treated at the UMGCC from 2000 to 2010. Results 65.9% were white, 30.7% were black and 3.3% were of other races. Blacks were less likely to present with oral cavity cancer (OC), and more likely to present with laryngeal or hypopharyngeal cancers. Whites were more likely to have early stage disease, especially in the OC. Black race was independently associated with worse OS in the entire cohort. Blacks had a significantly worse OS amongst OC and oropharyngeal cancers (OPC), with the largest disparity in OPC. However in multivariate analysis race was only still significant in OPC. Conclusion We observed differences by race in distribution of disease site, stage, and OS. Survival disparity in the entire cohort was driven mostly by differences amongst OPC.

1,25-(OH)2-Vitamin D3, the active metabolite of vitamin D, is a secosteroid hormone with known differentiating activity in leukemic cells. Studies have demonstrated the presence of vitamin D receptors (VDR) in a wide range of tissues and cell types. Antiproliferative activity of 1,25-(OH)2-vitamin D3 has been documented in osteosarcoma, melanoma, colon carcinoma, and breast carcinoma cells. This study was designed to analyze vitamin D receptor level in breast cancer cells as a marker of differentiation and as a predictor of growth inhibition by 1,25-(OH)2-vitamin D3. VDR messenger RNA was found to be present in relatively high levels in well-differentiated cells and in low levels in poorly differentiated cells. All cell lines had detectable VDR mRNA. Radiolabeled ligand binding assay showed a similar pattern. MCF-7 and T47D cells, which express VDR at moderate levels, showed significant growth inhibition by 10(-9) M1,25-(OH)2-vitamin D3 (p < 0.05). MDA-MB-231 cells, which have very low levels of VDR, demonstrated no growth inhibition by 1,25-(OH)2-vitamin D3 at concentrations up to 10(-6) M. Based on these results it can be stated that VDR expression is lost with de-differentiation and that receptor is essential for the antiproliferative response to 1,25-(OH)2-vitamin D3.

Loss of heterozygosity (LOH) at the mannose 6-phosphate/insulin-like growth factor 2 receptor gene locus (M6P/IGF2R) on 6q26-27 has recently been demonstrated in approximately 30% of both invasive and in situ breast cancers. LOH was coupled with somatic point mutations in the remaining allele in several instances, leading to the proposition that M6P/IGF2R is a tumor suppressor gene. Somatic mutations in M6P/IGF2R have also been described in hepatoma and gastrointestinal cancers with the replication error positive (RER+) phenotype. These data indicate that M6P/IGF2R loss of function mutations may be involved in the pathogenesis of a wide spectrum of malignancies. Extensive data on the normal function of the M6P/IGF2R suggest that loss of M6P/IGF2R activity may contribute to multiple aspects of tumor pathophysiology, including deregulated growth, apoptosis, angiogenesis and invasion.

No abstract

While we previously reported a striking racial difference in the prevalence of human papillomavirus (HPV) positive oropharyngeal cancer (OPSCC), less is known about differences in outcomes and trends over time in OPSCC by HPV status and race. We conducted a retrospective analysis of 467 OPSCC patients treated at the University of Maryland Greenebaum Cancer Center between 1992 and 2007, of which 200 had tissue available for HPV16 testing. HPV16 positive patients were significantly more likely to be white, with 45.5% of whites and 15.5% of blacks testing positive for HPV16. There was a significant increase in HPV16 positive OPSCC for all patients over time from 15.6% in 1992-1995 to 43.3% in 2004-2007 (p=.01). From 1992-1995, 33% of white patients were HPV16 positive with no black patients positive. From 2004-2007, 17.7% of black patients and 54% of white patients were HPV16 positive. White and black patients with HPV16 positive tumors had an identical and favorable overall survival (OS)(median 8.1 and 8.1 years, respectively ). However among HPV16 negative patients, whites had an improved OS compared to blacks (median 2.3 vs. 0.9 years, respectively, p = .02) including when analyzed in a multivariable Cox regression model. From 1992 to 2007 the percentage of HPV16 positive OPSCCs increased for white patients and was seen for the first time in black patients. While survival for HPV positive black and white patients was similar and favorable, outcomes for HPV negative patients were poor, with blacks having worse survival even after controlling for baseline characteristics.