A high prevalence of hr and lr HPV infections was detected in the OSCC patients included in the study. Moreover, hr HPV positivity was correlated with a decreased 5-year disease-free survival rate compared with HPV- and lr HPV+.

PurposeWe examined p16, p21 and p53 expression in combination with the presence of human papillomavirus (HPV) DNA as molecular markers to predict survival in patients with stage IV hypopharyngeal squamous cell carcinoma (HSCC).MethodsParaffin-embedded tumours from HSCC patients (n = 75) were evaluated for p16, p21 and p53 expression by immunohistochemistry. HPV DNA was detected by GP5+/6+ consensus PCR and subsequent genotyping by E6/E7 type-specific PCR for HPV types 6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66 and 68.ResultsAmong the 61 specimens that tested positive for the β-globin, HPV typing identified 50 patients with high-risk (hr) HPV types. HPV 16E7 DNA was detected in 74% (37 cases) of these specimens. Twelve patients were found to be infected with multiple HPV types. However, the presence of hrHPV DNA was not found to correlate with the proportion of disease-free patients. The 5-year disease-free survival rate was 73% in p53− tumours versus 48% in p53+ tumours (P = 0.008).ConclusionIn our series of patients with stage IV HSCC, the hrHPV+ subgroup had a similar prognosis (in terms of recurrence risk) as the HPV− subgroup. p53 overexpression was associated with a worse prognosis.

In TFTs, oncogenic and nononcogenic HPVs were present at a relatively high frequency in children and adults. The presence of high-risk HPV DNA in young children supports the horizontal transmission hypothesis and argues in favor of HPV vaccination at birth.

We investigated the prevalence of human papillomavirus (HPV) in a clinical series of 72 patients with head and neck squamous cell carcinoma (HNSCC) using a retrospective and prospective study design. The majority of patients were smokers and/or drinkers and were treated with concomitant chemoradiotherapy (CCR). Furthermore, we assessed the impact of HPV positivity on the response to CCR. Paraffin-embedded samples from HNSCC patients (n=72) were evaluated for the presence of HPV DNA using both GP5+/GP6+ consensus PCR and type-specific E6/E7 PCR to detect HPV types 6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 67 and 68. The type-specific E6/E7 PCR demonstrated that 20 out of 69 HNSCC patients (29%) presented with high-risk (HR) HPV types and that 5 of the 69 HNSCC patients (7%) presented with low-risk (LR) HPV types. Using the GP5+/GP6+ PCR, we observed that the rate of response was statistically lower in the HPV+ group (P=0.02). Concerning patient outcomes in terms of recurrence and survival, we observed that the prognosis was poorer for HPV+ patients. We showed for the first time that patients with HPV+ HNSCC present with a worse prognosis after CCR. This observation highlights the need for prospective studies with large numbers of patients and a detailed history of tobacco and alcohol consumption before validating HPV as a marker of prognosis following CCR.

BACKGROUND: C-X-C ligand (CXCL) chemokines exert major roles in the biologic aggressiveness of esophageal cancer. In the current study, the authors investigated temozolomide (TMZ)-induced effects on activity of the CXCL chemokine network in human esophageal cancer cells. To the authors' knowledge, TMZ has not been investigated previously in experimental or clinical esophageal cancers. METHODS: A complete mapping of CXCL chemokines and their receptor messenger RNA was performed in 2 established human esophageal cancer cell lines (OE21 and OE33) and in 4 surgical samples from patients with esophageal carcinoma. The analyses pointed out the potential importance of CXCL2, and monitoring CXCL2 with quantitative videomicroscopy indicated that its biologic activity was silenced in OE21 esophageal cancer cells. TMZ-mediated antitumor activity was determined in vivo in an OE21 metastatic nude mice xenograft model. RESULTS: The messenger RNA levels of CXC chemokines and their receptors were similar in both cell lines and in the 4 surgical specimens. CXCL2 depletion by small interfering RNA (siRNA) displayed marked effects on the proliferation of transfected OE21 cells. Chronic in vitro TMZ treatment of OE21 and OE33 cells markedly decreased CXCL2 and CXCL3 secretion. In vivo, TMZ induced significant delays in OE21 xenograft tumor development and improved the survival of OE21 xenograft-bearing mice, whereas cisplatin did not. Analyses performed on tissue samples from in vivo experiments revealed that TMZ also impaired tumor angiogenesis. CONCLUSIONS: The current study emphasized the role of proangiogenic chemokines in esophageal cancer biology and indicated the possibility of using TMZ as a clinically compatible drug to impair the actions of the CXCL chemokine network in esophageal cancers.