Head And Neck Squamous Cell Carcinoma Recurrence Research Articles

Does 18fluoro‐fluorodeoxyglucose positron emission tomography improve recurrence detection in patients treated for head and neck squamous cell carcinoma with negative clinical follow‐up?

The aim of this study was to determine the benefits of 18fluoro-fluorodeoxyglucose positron emission tomography (18F-FDG PET) in the detection of head and neck squamous cell carcinoma (HNSCC) recurrence in patients with negative clinical follow-up. Whole-body 18FDG-PET was performed in 30 patients treated for HNSCC without any clinical element for recurrence. Twenty-one negative PET and 9 positive results were seen. One patient with abnormal 18F-FDG uptake in the laryngeal area did not have recurrent HNSCC (false positive). Eight had proven recurrence. The sensitivity and specificity of 18F-FDG PET for the diagnosis of HNSCC recurrence were 100% (8/8) and 95% (21/22), respectively. The positive predictive value was 89% (8/9). The negative predictive value was 100% (21/21). The overall accuracy was 97% (29/30). The results of our study confirm the high effectiveness of 18F-FDG PET in assessment of HNSCC recurrence and suggest that it is more accurate than conventional physical examination follow-up alone.

Serum hepatocyte growth factor as a marker of tumor activity in head and neck squamous cell carcinoma

Hepatocyte growth factor (HGF) has previously been reported to be elevated in the serum of patients with malignancy, including breast, colorectal and gastric cancers. Here, we evaluated the correlation between serum HGF and the progression of head and neck squamous cell carcinoma (HNSCC). The mean serum HGF levels in 71 healthy control subjects, 78 patients with primary HNSCC, and eight patients with recurrent HNSCC were 0.538+/-0.163, 0.701+/-0.252, and 0.925+/-0.349ng/ml, respectively. The increase in the HGF level was significantly correlated with tumor stage progression. The HGF level had decreased to normal at 1 month after curative resection of the tumors. During follow-up for several months, the HGF level significantly increased in recurrent HNSCC patients, whereas there was no increase in nonrecurrent patients. Our data suggest that serum HGF is significantly corrected with tumor progression and may be a strong predictor of recurrence in HNSCC.

Frequent alterations of Smad signaling in human head and neck squamous cell carcinomas: a tissue microarray analysis.

Head and neck squamous cell carcinoma (HNSCC) ranks as the sixth most frequent cancer worldwide. HNSCC cell lines are typically refractory to transforming growth factor-beta (TGF-beta)-mediated cell cycle arrest. A number of these cell lines carry inactivating mutations of the TGF-beta type II (TbetaR-II) receptor, and fail to phosphorylate receptor-associated Smads, Smad2 and Smad3. In addition, we identified several intragenic mutations of the TbetaR-I gene in a small series of metastatic HNSCC specimens, suggesting that disruptions of TGF-beta signaling might contribute to the development and progression of HNSCC. To test this idea, we have now embarked on a larger scale analysis of the patterns of expression and activation of Smads in 170 HNSCC specimens assembled in tissue microarrays. Smad2 protein was expressed by 99% (95% CI: 96-100%) of tumors. The activated form of Smad2, pSmad2, was expressed in 86% (95% CI: 80-91%) of HNSCC, indicating their ability to survive and proliferate in spite of the presence of bioactive TGF-beta within the tissue microenvironment. In the 24 remaining cases (14%; 95% CI: 9-20%), pSmad2 was not detected in the tumor cells, although it was expressed by surrounding stromal cells and capillaries. In addition, 38 tumors (22%; 95% CI: 16-29%) failed to express Smad4 protein. Thus, we found evidence of loss of TGF-beta/Smad signaling in approximately 15-20% of HNSCC specimens, which is consistent with the phenotype of established human SCC lines. Moreover, we found that these Smad signaling defects were associated with a greater tendency for metastatic spread and regional or distant recurrence of HNSCC. These results indicate that inactivation of TGF-beta/Smad signaling occurs frequently in HNSCC and might have an adverse effect on patient outcome.

Soluble Tie-2 receptor levels independently predict locoregional recurrence in head and neck squamous cell carcinoma.

This study assessed two circulating angiogenic receptors as tumor markers in patients with head and neck squamous cell carcinoma (HNSCC): soluble vascular endothelial factor growth receptor-1 (sVEGFR1) and soluble Tie-2 receptor (sTie2R). Sera from 79 newly presenting patients with HNSCC and from 22 controls were assayed using sandwich ELISA. Median follow-up was 35 months after curative treatment. Analysis was carried out to compare levels between HNSCC patients and controls and to ascertain relationships with clinicopathologic and outcome variables. Soluble VEGFR1 was not elevated in the HNSCC group and was not related to any of the clinicopathologic or outcome variables. Soluble Tie2R was also not elevated in HNSCC patients or related to the clinicopathologic variables but was associated with locoregional recurrence (p =.009). Raised sTie2R (>64 ng/mL) independently predicted recurrence (p =.007) with a relative risk of 3.0 (95% CI, 1.7-5.0). Soluble Tie2R is an independent predictor of locoregional recurrence in HNSCC.

9p21 deletion correlates with recurrence in head and neck cancer.

Deletion of 9p21 is a common event in many human tumors, including head and neck squamous cell carcinoma (HNSCC). The gene CDKN2, which encodes the protein p16, a cyclin-dependent kinase-4 inhibitor, maps to 9p21. The role of CDKN2 as the tumor suppressor gene in these neoplasms is unclear. The role of loss of heterozygosity (LOH) as a prognostic tool has not been described in HNSCC. We performed deletion mapping using Southern and PCR-based LOH analysis and prospective survival analysis. We demonstrate that LOH of 9p and, specifically, the interferon (IFN) gene cluster correlates with recurrence of HNSCC. We also demonstrate two separate areas of deletion on 9p, one centromeric to IFNbeta and telomeric to CDKN2 and the other centromeric to CDKN2 and telomeric to the polymorphic marker D9S19. All the deletions involve either the markers IFNalpha and/or D9S171 and D9S126 but not necessarily CDKN2. These results suggest another tumor suppressor gene (TSG) may be involved in HNSCC carcinogenesis and may play a role in aggressive disease as manifest by local, regional, or distant recurrence.