MicroRNA-125b Interacts with Foxp3 to Induce Autophagy in Thyroid Cancer.

Thyroid cancer is rapidly increasing in incidence worldwide. Although most thyroid cancer can be cured with surgery, radioactive iodine, and/or chemotherapy, thyroid cancers still recur and may become chemoresistant. Autophagy is a complex self-degradative process that plays a dual role in cancer development and progression. In this study, we found that miR-125b was downregulated in tissue samples of thyroid cancer as well as in thyroid cancer cell lines, and the expression of Foxp3 was upregulated. Further, we demonstrated that miR-125b could directly act on Foxp3 by binding to its 3' UTR and inhibit the expression of Foxp3. A negative relationship between miR-125b and Foxp3 was thus revealed. Overexpression of miR-125b markedly sensitized thyroid cancer cells to cisplatin treatment by inducing autophagy through an Atg7 pathway in vitro and in vivo. Taken together, our findings demonstrate a novel mechanism by which miR-125b has the potential to negatively regulate Foxp3 to promote autophagy and enhance the efficacy of cisplatin in thyroid cancer. miR-125 may be of therapeutic significance in thyroid cancer.

The role of human papillomavirus in laryngeal cancer in Southern China.

To delineate the role of human papillomavirus (HPV) in laryngeal cancer in Southern Chinese, a retrospective cross-sectional study was conducted in a major otorhinolaryngology referral center in Hong Kong. Eighty-five Chinese patients with histology-confirmed laryngeal squamous cell carcinoma (LSCC) diagnosed between 2005 and 2010 were examined for the status of HPV by PCR, and the expression of p16 and p53 by immunohistochemistry. The HPV, p16 and p53 findings were correlated with clinicopathological features, recurrence and 5-year survival. HPV DNA was detected in one patient (1.2%, 95%CI: 0.2-6.4%) who had glottic cancer and harbored HPV-6. Overexpression of p16 and p53 were detected in 11 (12.9%) and 47 (55.3%) cases, respectively. Recurrence occurred in 22.4% of patients at a median of 13 months. The 5-year overall survival and disease-specific survival were 55.7% and 72.4%, respectively. Overexpression of p16 or p53 was not associated with clinicopathological features, recurrence or overall survival. HPV plays a limited role in laryngeal cancer in Hong Kong Southern Chinese. In contrast to oropharyngeal cancer, p16 cannot be used as a surrogate marker for oncogenic involvement of HPV and cannot predict survival in laryngeal cancer.

Expression of Antioxidant Molecules and Heat Shock Protein 27 in Thyroid Tumors.

Oxidative stress-induced DNA damage is a known causing factor for many types of tumors, but information on the role of oxidants and antioxidants in thyroid tumors is limited. The aim of this study was to determine antioxidant levels in thyroid tumors. In this study, tumor and its matched non-tumor thyroid tissue samples were obtained from 53 patients with thyroid tumors. The levels of manganese superoxide dismutase (MnSOD), thioredoxin reductase 2 (TXNRD2), glutathione (GSH), glutathione peroxidase (Gpx), catalase (CAT), and 27 kd heat-shock protein (hsp27) were determined in both thyroid tissue samples and cultured thyroid cells by immunohistochemical staining and western blot. Hydrogen peroxide (H2 O2 ) was used to generate oxidant stress in the cell culture experiments. We found that the levels of MnSOD, TXNRD2, GSH, Gpx, and Hsp27 were increased in both malignant and benign tumors, while the level of CAT was decreased. To verify the results of the tissue study, we treated cultured thyroid cells with H2 O2 and found the same pattern of antioxidant changes. Hsp27 was also increased after H2 O2 treatment. The expression of hsp27 was upregulated by 8.24-, 6.96-, and 3.09-fold in thyroid cancer, follicular adenoma, multinodular goiter, respectively. Collectively, our study demonstrated that the levels of hsp27 together with MnSOD, TXNRD2, GSH, and Gpx were significantly upregulated by H2 O2 in thyroid tumors. The increase of these antioxidants is observed in both malignant and benign tumors, particularly in the former. The upregulation of antioxidants is likely a protective mechanism of tumor cells to maintain their survival and growth. J. Cell. Biochem. 117: 2473-2481, 2016. © 2016 Wiley Periodicals, Inc.

The role of human papillomavirus in head and neck squamous cell carcinoma: A case control study on a southern Chinese population.

HPV plays a role in the development of a portion of head and neck squamous cell carcinoma (HNSCC), but only limited information on its role in southern Chinese population is available. A multicenter case-control study was conducted. HPV type, viral integration, E6/7 mRNA expression status, and TP53 mutation were determined. A total of 228 HNSCC were recruited including 137 (60.1%) oral SCC, 34 (14.9%) oropharyngeal SCC, 31 (13.6%) laryngeal SCC, 21 (9.2%) hypopharyngeal SCC, and 5 (2.2%) lip and paranasal sinus SCC. High-risk HPV infection was found in 7.5% (17/228) of HNSCC, but only a small proportion of samples had evidence of viral integration (5.3%, 12/228) or E6/7 mRNA expression (4.4%, 10/228). HPV infection with oncogenic phenotype (integration and E6/7 mRNA expression) was significantly more common in oropharyngeal SCC than controls (9/34, 26.5% vs. 0/42, 0.0%, P < 0.001). Smoking showed a significant association with HNSCC, oropharyngeal SCC, and laryngeal SCC. TP53 mutation was associated with HNSCC (P < 0.001). Older age, TP53 mutation, and HPV16 infection with oncogenic phenotypes were independently associated factors for HNSCC with odds ratios of 1.03 (1.02-1.05), 3.38 (1.71-6.66), and 9.19 (1.13-74.68), respectively. High-risk HPV infection of head and neck mucosa is not uncommon in the Hong Kong population. This study found that 26-30% of oropharyngeal carcinoma was associated with HPV infection, mostly HPV16, and that smoking which predisposes to TP53 mutations was another important risk factor.

The cross-talk between estrogen receptor and peroxisome proliferator-activated receptor gamma in thyroid cancer.

BACKGROUND: Estrogen receptor (ER) and peroxisome proliferator-activated receptor gamma (PPARγ) are associated with thyroid tumorigenesis and treatment. However, the interaction between them has not been studied. METHODS: The impact of ER over-expression or down-expression by DNA/small interfering RNA (siRNA) transfection, ERα agonists, and the ERß agonist diarylpropiolnitrile (DPN) on PPARγ expression/activity was examined in papillary thyroid carcinoma (PTC) and anaplastic thyroid carcinoma (ATC) cells. The effects of PPARγ modulation by rosiglitazone (RTZ), a PPARγ ligand, and of PPARγ siRNA on ER expression were determined. Cellular functions reflected by cell proliferation and migration were assayed. Apoptosis was analyzed by terminal deoxynucleotidyl transferase dUTP nick-end labeling, and apoptotic-related proteins were evaluated by Western blot analysis. RESULTS: PPARγ protein and activity were reduced by the over-expression of either ERα or ERß, whereas repression of ERα or ERß increased PPARγ expression. The administration of RTZ counteracted the effects of ER and also reduced their expression, particularly in PTC cells. Moreover, knockdown of PPARγ increased ER expression and activity. Functionally, ERα activation offset the inhibitory effect of PPARγ on cellular functions, but ERß activation aggregated it and induced apoptosis, particularly in PTC cells. Finally, the interaction between ERß and PPARγ enhanced the expression of proapoptotic molecules, such as caspase-3 and apoptosis-inducing factor. CONCLUSIONS: This study provides evidence supporting a cross-talk between ER and PPARγ. The reciprocal interaction between PPARγ and ERß significantly inhibits the proliferation and migration of thyroid cancer cells, providing a new therapeutic strategy against thyroid cancer.

Prevalence and interpretation of AFF immunostain of DEK::AFF2 fusion-associated papillary squamous cell carcinoma in a retrospective cohort of recurrent sinonasal papillomas.

DEK::AFF2 fusion-associated papillary squamous cell carcinoma is a novel entity characterized by its unique translocation and malignant clinical course. In this study, AFF immunohistochemistry (IHC) was performed in recurrent sinonasal papillomas for reviewing the prevalence of undiagnosed DEK::AFF2 carcinomas and to investigate the performance of AFF IHC in diagnosis of DEK::AFF2 carcinomas. Recurrent sinonasal papillomas after surgical excision in a two-decade period were retrieved. Histologic slides were reviewed for features of DEK::AFF2 carcinoma. AFF IHC was performed, and cases with any (> 1%) nuclear positivity were validated by DEK break apart fluorescence in situ hybridization. Totally 43 cases were included, comprising 28 inverted, 6 exophytic, one oncocytic, and 8 non-specified sinonasal papillomas. Five (11.6%) cases exhibited positivity to AFF IHC. Three cases exhibited patchy weak to moderate staining intensity predominantly in a granular cytoplasmic pattern. Two cases exhibited strong and diffuse (> 90%) nuclear staining. Cases showing weak staining were negative for DEK rearrangement, while those with strong staining were positive. Both cases of DEK::AFF2 carcinoma showed aggressive behavior with extensive local invasion and nodal metastasis. Background stromal plasma cells, when present, consistently showed strong and diffuse staining. AFF IHC was further performed in plasmacytoma samples as control and showed strong and diffuse immunoreactivity. A significant minority of recurrent sinonasal papillomas represent DEK::AFF2 carcinomas. Granular, cytoplasmic, or incomplete AFF staining should be considered as negative. In view of the rarity of DEK::AFF2 carcinomas, plasma cells and plasma cell neoplasms are potential for internal and surrogate external controls.

Changes in the Incidence and Human Papillomavirus-Positive Portion of Oropharyngeal Squamous Cell Carcinoma in Hong Kong.

The incidence of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) is rising in the West, but little is known in Asia. This study elucidated changes in the incidence and HPV-positive portion of OPSCC in Hong Kong. Data from population-based cancer registry were used to analyze the incidence of OPSCC in association with other head and neck cancers. Archived tumor tissues were tested for HPV. From 1986 to 2020, there was a marked decrease in the incidence of nasopharyngeal and laryngeal cancers, but a persistent increase in OPSCC from 36 cases in 1986 to 116 cases in 2020. The average positive rate for high-risk HPV was 36.1% (112/310) among OPSCC diagnosed in 2010-2020. The HPV-positive rate in recent years was significantly higher than earlier cases (tonsil SCC: 64.7% (55/85) in 2016-2020 vs. 40.4% (19/47) in 2010-2015, p = 0.007). Patients with HPV-positive tonsil cancers were significantly younger than those negative (mean [SD]: 58.9 [9.9] vs. 64.3 [13.3] years, p = 0.006), but no significant difference was observed between genders. A persistent increase in the incidence of oropharyngeal cancer over the last few decades was observed in Hong Kong, which can be explained by the remarkable increase in HPV-positive tonsil cancers.

The First Report of Cytology of DEK::AFF2 Fusion-Associated Papillary Squamous Cell Carcinoma on Fine-Needle Aspiration.

DEK::AFF2 fusion-associated papillary squamous cell carcinoma is a recently characterized sinonasal malignancy defined by its unique translocation. DEK::AFF2 carcinomas may be deceptively monotonous and lack keratinization, resembling transitional epithelium. The lack of traditional cytological atypia presents diagnostic challenges. Our case describes the first report of fine-needle aspiration cytology of a lymph node involved by DEK::AFF2 carcinoma in a patient with previously resected sinonasal inverted papilloma with carcinomatous transformation six years prior to presentation. This aspirate consisted of a lymphoid-rich background admixed with a moderate amount of epithelial cells arranged in cohesive structures of variable size, including large sheets. The tumor cells resembled those of the corresponding biopsy, featuring mildly hyperchromatic nuclei with fine to vesicular chromatin. Lesional cells lacked keratinization, mitoses, or hyperchromasia. Our finding suggests that in nodal aspirates of patients with a history of sinonasal-type papillomas, especially those with prior malignant transformation or atypia, there should be consideration for the possibility of DEK::AFF2-related primary. When in doubt, DEK FISH of AFF2 immunohistochemistry should be performed for confirmation.

Aspiration cytology of pleomorphic adenoma with squamous metaplasia: A case series and literature review illustrating diagnostic challenges.

OBJECTIVE: Squamous metaplasia is not uncommonly observed in salivary gland neoplasms, including pleomorphic adenomas (PAs). It poses as a diagnostic pitfall with cytomorphologic features overlapping with low-grade epithelial malignances and carcinoma ex-PA. We report series of aspirates of PAs with squamous metaplasia and review the literature for the clinicopathological and cytologic features of this diagnostically challenging entity. METHODS: Three cases including index aspiration cytology, post-aspiration specimen cytology, cell block immunohistochemistry (IHC), histologic correlation, and clinical data were reviewed. Literature search was performed for cases of PAs with squamous metaplasia, yielding 22 case reports including 11 with aspiration cytology performed. RESULTS: Metaplastic squamous components were seen in all index aspirations, but foreign body reaction and cystic changes were observed only after aspiration or in irritated lesions. PLAG1 IHC demonstrated reliable immunoreactivity in cell block preparations. Summarizing cases in this series and in the literature, cytologic features reported were variable and no consistent diagnostic feature was identified. Most reported cases were initially diagnosed as suspicious or malignant, but all ran a benign clinical course. Significant morbidity was reported only in one case due extensive surgery based on a malignant diagnosis. CONCLUSIONS: Squamous metaplasia in PAs is not associated with adverse outcomes, but may induce reactive changes upon aspiration/irritation, resulting in worrisome cytologic features. PLAG1 IHC is a useful adjunct when characteristic cytologic features for PAs are absent or obscured. Prudent use of the diagnostic category salivary gland neoplasm of uncertain malignant potential (SUMP) in the Milan system can avoid overtreatment.

SMARCB1 (INI1)-Deficient Sinonasal Carcinoma with Yolk Sac differentiation Showing Co-loss of SMARCA4 Immunostaining - A Case Report and Literature Review.

SMARCB1 (INI1)-deficient carcinoma of the sinonasal tract is a rare and distinct entity characterized by the loss of INI1 immunostain expression. These tumors are morphologically diverse, with isolated cases of yolk sac differentiation reported. We report the first case of SMARCB1-deficient sinonasal carcinoma that demonstrated co-loss of SMARCA4 immunostain, and reduced SMARCA2 and ARID1A staining, with the entire tumor showing histological and immunohistochemical evidence of yolk sac differentiation. The clinical, histological, immunohistochemical and molecular features were discussed and compared against SMARCB1-deficient sinonasal carcinomas with yolk sac differentiation and SMARCA4-deficeint sinonasal carcinomas reported in the literature. With a highly aggressive clinical course leading to mortality two months after presentation, the behavior of this tumor appears to be more comparable to that of SMARCA4-deficient sinonasal carcinomas. A comprehensive immunopanel including SMARCB1, SMARCA4, SMARCA2 and ARID1A may be advisable for assessment and prognostication of SWI/SNF-deficient tumors.

The Role of Arginine Metabolism in Oral Tongue Squamous Cell Carcinoma.

Early diagnosis and treatment do not prevent the high morbidity and poor prognosis of oral tongue squamous cell carcinoma (TSCC). Earlier studies have shown that ARG1 signaling is deregulated in TSCC. Here, we investigated the complexity of ARG1 metabolism in this cancer subsite to appreciate the therapeutic potential of this potential biological vulnerability. Various functional studies show that ARG1 overexpression in oral cancer cells inhibits cell proliferation and invasion compared with controls. Further, RNA-sequencing revealed numerous differentially expressed genes (DEGs) and associated networks were dysregulated by ARG1 overexpression, including hypoxia-inducible factor (HIFα) signaling, the natural killer cell signaling pathway and interferon signaling. Our work provides a foundation for understanding the mechanism of action of disrupted arginine metabolism in oral tongue squamous cell carcinoma. This may impact the community for developing further therapeutic approaches.

Reversal of pale-to-dark nasopharyngeal follicle ratio on narrow-band imaging.

Normal nasopharyngeal mucosa contains varying amounts of lymphoid tissue, which in adults may be minimal or absent. Nasopharyngeal mucosa with minimal lymphoid tissue has a regular follicular pattern on narrow-band imaging; pale follicles have thin, dark borders and the ratio of the pale follicle to the dark border (pale-to-dark ratio) is roughly 90%. In some patients undergoing routine nasopharyngeal endoscopy, the pale-to-dark ratio is reversed on narrow-band imaging, with dark centres surrounded by pale borders and a pale-to-dark ratio of roughly 50%. These dark follicles may represent abnormal capillary loops, as they have the same appearance as microvascular changes seen on narrow-band imaging of the oesophageal mucosa which indicate dysplasia or malignancy. While this observed change in the follicular pattern may be an early event in the evolution of nasopharyngeal carcinoma, the significance of this finding remains to be confirmed by a larger-scale study.

The Intersection between Oral Microbiota, Host Gene Methylation and Patient Outcomes in Head and Neck Squamous Cell Carcinoma.

The role of oral microbiota in head and neck squamous cell carcinoma (HNSCC) is poorly understood. Here we sought to evaluate the association of the bacterial microbiome with host gene methylation and patient outcomes, and to explore its potential as a biomarker for early detection or intervention. Here we performed 16S rRNA gene amplicon sequencing in sixty-eight HNSCC patients across both tissue and oral rinse samples to identify oral bacteria with differential abundance between HNSCC and controls. A subset of thirty-one pairs of HNSCC tumor tissues and the adjacent normal tissues were characterized for host gene methylation profile using bisulfite capture sequencing. We observed significant enrichments of Fusobacterium and Peptostreptococcus in HNSCC tumor tissues when compared to the adjacent normal tissues, and in HNSCC oral rinses when compared to healthy subjects, while ten other bacterial genera were largely depleted. These HNSCC-related bacteria were discriminative for HNSCC and controls with area under the receiver operating curves (AUCs) of 0.84 and 0.86 in tissue and oral rinse samples, respectively. Moreover, Fusobacterium nucleatum abundance in HNSCC cases was strongly associated with non-smokers, lower tumor stage, lower rate of recurrence, and improved disease-specific survival. An integrative analysis identified that enrichment of F. nucleatum was associated with host gene promoter methylation, including hypermethylation of tumor suppressor genes LXN and SMARCA2, for which gene expressions were downregulated in the HNSCC cohort from The Cancer Genome Atlas. In conclusion, we identified a taxonomically defined microbial consortium associated with HNSCC that may have clinical potential regarding biomarkers for early detection or intervention. Host-microbe interactions between F. nucleatum enrichment and clinical outcomes or host gene methylation imply a potential role of F. nucleatum as a pro-inflammatory driver in initiating HNSCC without traditional risk factors, which warrants further investigation for the underlying mechanisms.

Clinicopathological features of melanotic and non-melanotic oncocytic lesions of the nasopharynx.

Oncocytic metaplastic lesions of the nasopharynx are rare benign entities which are divided into melanotic and non-melanotic forms. Less than 40 non-melanotic and 30 melanotic cases have been reported in the literature. We present the largest known case series to date of melanotic oncocytic metaplasia and more than 20 cases of non-melanotic oncocytic metaplasia. Clinical, endoscopic, histological and immunohistochemical features were reviewed. Most cases presented in males starting from their late adulthood. Compared to its non-melanotic counterpart, all cases of melanotic oncocytic metaplasia had a smoking history (p=0.041). All cases of melanotic oncocytic metaplasia were negative to melanocytic markers (S100, HMB-45, Melan-A and MiTF). Although no disease-related mortality was recorded, concurrent melanoma and nasopharyngeal carcinoma were seen in two cases.

Analysis of bone marrow fatty acid composition using high-resolution proton NMR spectroscopy.

High-resolution 1H NMR spectroscopy as a complementary method in the analysis of human bone marrow fatty acid (FA) composition was examined. Marrow FA composition in 10 bone samples measured by NMR and gas chromatography (GC) were compared. NMR T1 relaxation time of FA was determined and reproducibility tests were performed to assess the variability. Good correlations were obtained between the NMR and GC results for omega-6 polyunsaturated fatty acid (PUFA) (Spearman r, 0.878), omega-3 PUFA (0.895), monounsaturated FA (0.964) and saturated FA (0.939). The NMR method tended to overestimate saturated FA and underestimate omega-3/omega-6 ratio compared to GC results. T1 relaxation time of marrow FA was 0.56-3.65s. Coefficient of variation of the NMR method was 0.6-8.2% in intra-experimental and 0.2-8.4% in inter-experimental measurements. This study demonstrates a complementary role for 1H NMR spectroscopy as an additional analytical tool in human lipid research.

Case Report: Exome sequencing reveals recurrent RETSAT mutations and a loss-of-function POLDIP2 mutation in a rare undifferentiated tongue sarcoma.

Soft tissue sarcoma of the tongue represents a very rare head and neck cancer with connective tissue features, and the genetics underlying this rare cancer are largely unknown. There are less than 20 cases reported in the literature thus far. Here, we reported the first whole-exome characterization (>×200 depth) of an undifferentiated sarcoma of the tongue in a 31-year-old male. Even with a very good sequencing depth, only 19 nonsynonymous mutations were found, indicating a relatively low mutation rate of this rare cancer (lower than that of human papillomavirus (HPV)-positive head and neck cancer). Yet, among the few genes that are somatically mutated in this HPV-negative undifferentiated tongue sarcoma, a noticeable deleterious frameshift mutation (with a very high allele frequency of >93%) of a gene for DNA replication and repair, namely POLDIP2 (DNA polymerase delta interacting protein 2), and two recurrent mutations of the adipogenesis and adipocyte differentiation gene RETSAT (retinol saturase), were identified. Thus, somatic events likely affecting adipogenesis and differentiation, as well as potential stem mutations to POLDIP2, may be implicated in the formation of this rare cancer. This identified somatic whole-exome sequencing profile appears to be distinct from that of other reported adult sarcomas from The Cancer Genome Atlas, suggesting a potential unique genetic profile for this rare sarcoma of the tongue. Interestingly, this low somatic mutation rate is unexpectedly found to be accompanied by multiple tumor protein p53 and NOTCH1 germline mutations of the patient's blood DNA. This may explain the very early age of onset of head and neck cancer, with likely hereditary predisposition. Our findings are, to our knowledge, the first to reveal a unique genetic profile of this very rare undifferentiated sarcoma of the tongue.

Strong immunohistochemical expression of vascular endothelial growth factor predicts overall survival in head and neck squamous cell carcinoma.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) has high morbidity and mortality, and its relationship with tumor angiogenesis as measured by microvessel density (MVD) or vascular endothelial growth factor (VEGF) expression has shown mixed results, with some, but not others, reporting correlation with outcome. METHODS: A retrospective study of 186 patients with HNSCC was performed. Patients were evaluated for MVD and VEGF and to correlate the levels with clinical parameters, including age at diagnosis, sex, site of tumor, stage, survival (disease free and overall), pathological tumor grade, and the presence of lymph node metastases. RESULTS: The 186 cancers included the following sites: oral tongue (n = 69), palate (n = 9), maxillary sinus (n = 8), floor of mouth (n = 13), oropharynx (n = 27), hypopharynx (n = 26) and larynx (n = 34). Over three-quarters of patients had advanced tumor (stage III/IV) and 58.6% had lymph node metastases. MVD and VEGF were assessed in 166 and 164 cases, respectively, but these were not correlated with site and grade. The 3-year overall and disease-free survival rates were 55.4% and 53.2%, respectively. Both univariate and multivariate survival analysis showed that advanced T stage, nodal metastasis, and strong VEGF intensity were independent adverse predictors for overall and disease-free survival. In stage IV disease, strong VEGF immunoreactivity was found to be the single adverse factor affecting the overall survival and a contributory factor for disease-free survival. CONCLUSIONS: VEGF immunoreactivity is a strong predictor of adverse outcome, particularly in locoregionally advanced disease.

Prevalence, Clinicopathological Characteristics, and Outcome of Human Papillomavirus-Associated Oropharyngeal Cancer in Southern Chinese Patients.

BACKGROUND: Although the global incidence of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) is increasing, there is little information on southern Chinese population available. METHODS: We analyzed 207 patients which constituted 63.5% of all newly diagnosed OPSCC in Hong Kong during a 5-year period from 2005 to 2009. RESULTS: We used E6/7 mRNA as a marker of oncogenic involvement and found 20.8% (43/207) of OPSCC and 29.0% (36/124) of tonsillar SCC was associated with HPV. HPV-16 was identified in all cases except one (HPV-18). Patients with HPV-associated OPSCCs were significantly younger than HPV-negative patients (mean age: 59.8 vs. 63.9 years, P = 0.05). Multivariate analysis showed that HPV-associated OPSCC was more likely to occur in nonsmokers (39.5% vs. 15.1%, OR: 2.89, P = 0.05), nondrinkers (52.5% vs. 25.6%, OR: 2.72, P = 0.04), originate from the palatine tonsils (83.7% vs. 53.7%, OR: 3.88, P = 0.01), present with an early primary tumor (T1/2; 79.1% vs. 47.6%, OR: 3.81, P = 0.004), and exhibit basaloid differentiation (33.3% vs. 7.3%, OR: 19.74, P = 0.006). HPV positivity was an independent predictor for better prognosis for both 5-year overall and 5-year disease-specific survivals (DSS; 63.0% vs. 29.7%, HR: 0.33, P < 0.001, and 87.8% vs. 42.6%, HR: 0.16, P < 0.001, respectively). CONCLUSION: The estimated age-standardized incidence of OPSCC in Hong Kong during the period 2005-2009 was 0.12/100,000/year. IMPACT: This study has provided the most comprehensive clinical and pathologic information to date about this newly recognized disease in southern Chinese. In view of the global trend, we should anticipate and prepare for an increase in HPV-related OPSCC in southern China.

Quantitative analysis of cell-free Epstein-Barr virus DNA in plasma of patients with nonnasopharyngeal head and neck carcinomas.

PURPOSE: We investigated the detectability of EBV DNA in the plasma of patients with non-nasopharyngeal head and neck carcinomas (NNHNC). Previous studies have shown that EBV is present in the tumor tissue of some NNHNC. EXPERIMENTAL DESIGN: We recruited 101 patients with NNHNC and 48 healthy controls. Blood samples were taken from controls and patients before treatment. Tumor tissue samples were tested for the presence of EBV in the first 69 patients by in situ hybridization for small EBV-encoded RNA (EBER). Plasma EBV DNA was measured by real-time quantitative PCR in patients and controls. RESULTS: Squamous cell carcinoma (SCC) was the commonest histology (78 patients) followed by lymphoepithelial carcinoma (8 patients). EBER was detected in tumor cells in 7 of 69 patients tested. All of the EBER-positive tumors were lymphoepithelial carcinoma. Two controls (2 of 48; 4.2%) had detectable plasma EBV DNA. Plasma EBV DNA was detected in all of the patients with EBER-positive tumors, and in 23 of 94 (24.5%) patients with tumors of EBER-negative or unknown status. The proportion of plasma EBV DNA-positive cases in either group was significantly higher than that in the control group (P < 0.0027). Plasma EBV DNA concentrations in patients with EBER-positive tumors (median, 3827 copies/ml) were significantly higher than those in the controls (median, 0 copy/ml; P = 0.0001). Of patients with SCC, 21 (26.9%) had detectable plasma EBV DNA (median concentration, 34 copies/ml). Plasma EBV DNA concentrations in the whole group of patients with SCC (median, 0 copy/ml; interquartile range, 0-4 copies/ml) were also significantly higher than those in the controls (P = 0.001). CONCLUSIONS: Our data indicate that plasma EBV DNA reflects tumoral EBER status, and it may be of use as a tumor marker for EBER-positive NNHNC. The biological and clinical significance of low levels of circulating EBV DNA in the minority of patients with EBER-negative tumors remain to be elucidated.

In vivo 1H MR spectroscopy of thyroid carcinoma.

To determine if proton magnetic resonance spectroscopy (1H MRS) of thyroid carcinoma is feasible and to determine if 1H MRS spectra of malignant tumors differ from that of normal thyroid tissue. We performed 1H MRS at 1.5 T at echo-times (TE) 136 and 272 ms to examine eight patients with thyroid cancer (primary tumour or nodal metastasis) larger than 1 cm3 in size and five volunteers with normal thyroids. Spectra acquired from six primary tumors (three anaplastic carcinomas, two papillary carcinomas and one follicular carcinoma) and two nodes (two papillary carcinoma metastases) were analyzed in the time-domain using a non-linear least squares fitting algorithm with incorporation of prior knowledge. Choline (3.2 ppm) was identified in all solid carcinomas with a mean choline/creatine of 4.3 at TE 136 ms and 5.4 at TE 272 ms. Ratios for malignant tumors at TE 136 ms ranged from 1.6 in well differentiated follicular carcinoma to 9.4 in anaplastic carcinoma. No choline was detected in normal thyroid tissues. Our results showed that 1H MRS is a feasible technique for the evaluation of malignant thyroid tumors larger than 1 cm3 and that proton spectra of malignant tumors differ from that of normal thyroid tissue.