Comparison of clinical, radiological and morphological features including the distribution of HPV E6/E7 oncogenes in resection specimens of oropharyngeal squamous cell carcinoma.

BACKGROUND: Human papillomavirus (HPV)-driven oropharyngeal squamous cell carcinoma (OPSCC) represents a distinct tumour entity in comparison to HPV-negative OPSCC. The clinical, radiological, morphological features and distribution of HPV E6/E7 mRNA were investigated in resected specimens of OPSCC. METHODS: We retrieved formalin-fixed, paraffin-embedded whole section slides from 24 p16/HPV-DNA positive and 18 p16/HPV-DNA negative primary tumours and 16 corresponding metastases in patients with early-stage OPSCC who underwent planned curative or diagnostic primary transoral robotic surgery. A detailed clinicoradiological and histopathological investigation of the tumours was performed along with detection of HPV E6/E7 mRNA by in situ hybridisation. RESULTS: HPV-driven OPSCC was characterised by non-keratinising morphology and was dominated by a cohesive invasion pattern at the leading edge of the tumour. Dysplastic zones of the squamous epithelium were strictly located in the tonsillar crypts in contrast to HPV-negative OPSCC which predominantly arised from the dysplastic surface epithelium. Thirteen HPV-driven OPSCC invaded through the tonsillar lymphoid compartment and into soft tissue, causing a stromal desmoplastic reaction. HPV mRNA was consistently but inhomogenously expressed in the entire tumour area and in the dysplastic squamous epithelium. There was no HPV expression in the adjacent normal epithelium and in the non-neoplastic tissues. CONCLUSIONS: This study enhances the current understanding of HPV-driven OPSCC. Only tumours that invade through the lymphoid compartment induce a stromal desmoplastic reaction. A consistent but inhomogenous expression of E6 and E7 mRNA was found in tumour and dysplastic areas, emphasizing that the E6/E7 oncogenes are the driving factors in HPV-driven OPSCC.

Increased expression of TNF-alpha, IL-6, and IL-8 in HALS: implications for reduced adiponectin expression and plasma levels.

Human immunodeficiency virus (HIV)-associated lipodystrophy syndrome (HALS) is a side effect of highly active antiretroviral therapy of HIV-infected patients; however, the mechanism of the lipodystrophy and insulin resistance seen in this syndrome remains elusive. Adiponectin, an adipocyte-specific protein, is thought to play an important role in regulating insulin sensitivity. We investigated circulating levels and gene expression of adiponectin in subcutaneous abdominal adipose tissue (AT) from 18 HIV-infected patients with HALS compared with 18 HIV-infected patients without HALS. Implications of cytokines for adiponectin levels were investigated by determining circulating levels of TNF-alpha, IL-6, and IL-8 as well as gene expression of these cytokines in AT. HALS patients exhibited 40% reduced plasma adiponectin levels (P < 0.05) compared with non-HALS subjects. Correspondingly, adiponectin mRNA levels in AT were reduced by >50% (P = 0.06). HALS patients were insulin resistant, and a positive correlation was found between plasma adiponectin and insulin sensitivity (r = 0.55, P < 0.01) and percent limb fat (r = 0.61, P < 0.01). AT mRNA of TNF-alpha, IL-6, and IL-8 was increased in AT of HALS subjects (P < 0.05), and both AT TNF-alpha mRNA and plasma TNF-alpha were negatively correlated to plasma adiponectin (P < 0.05). Finally, TNF-alpha was found in vitro to inhibit human AT adiponectin mRNA by 80% (P < 0.05). In conclusion, HALS patients have reduced levels of plasma adiponectin and adiponectin mRNA in AT. Increased cytokine mRNA in AT is hypothesized to exert an inhibitory effect on adiponectin gene expression and, consequently, to play a role in the reduced plasma adiponectin levels found in HALS patients.