Prevalence of novel gamma HPV types 223 and 225 in oral cavity and skin of Indian normal and neoplastic participants.

Gamma-papillomaviruses, though traditionally classified as cutaneotropic, actual tissue tropism is largely unexplored. This study aimed to evaluate the tissue-specific prevalence of two novel-HPV 223 and 225 in samples of oral mucosa and keratinized epithelium of varied skin parts from 226 female and male subjects, with or without neoplastic/dysplastic lesions in oral cavity or cervix. The gamma-human papillomavirus (gamma-HPV) 223 and 225 DNA presences were determined by polymerase chain reaction (PCR) ursing the HPV type-specific primers and confirmed by Sanger sequencing. Viral load in the HPV 223 and HPV 225 positive samples were determined by absolute real-time quantification method. Alpha-HPV DNA prevalence was also checked in oral mucosa to ascertain coinfection status. Novel HPV 223 was present in 4.4% (10/226) oral mucosal samples of the study population; interestingly all were females with no prevalence in their corresponding skin swab samples. Whereas, the prevalence of HPV 225 was found both in the skin and oral mucosa of 28.2% (N = 37/131) female and 17.9% (N = 17/95) male participants. Alongside, HPV 223 viral load was found to be significantly higher (p = 0.02 < 0.05) in the oral mucosa of diseased participants, whereas, HPV 225 viral load was higher in the oral mucosa of normal participants. Our results suggest that gamma-HPV 223 has its prevalence only in the oral mucosal epithelium, whereas, HPV 225 has its prevalence on both mucosal and keratinized skin epithelium, indicating its dual tropism nature.

Cannabis smoke can be a major risk factor for early-age laryngeal cancer--a molecular signaling-based approach.

Epidermal growth factor receptor (EGFR) and its downstream elements are overexpressed in most cases of the head and neck squamous cell carcinoma. This study investigated the expression pattern of key proteins linked to the EGFR pathway in laryngeal carcinoma patients with a history of cannabis smoking. We selected 83 male glottic cancer patients, aged between 45 to 75 years with three distinct populations-nonsmoker, cigarette smoker, and cannabis smoker. Immunohistochemical staining was performed for EGFR, protein kinase B (PKB or Akt), nuclear factor kappa B p50 (NF-КB), and cyclooxygenase-2 (COX-2) followed by boolean scoring for statistical analysis. Experimental data showed upregulation of the selected EGFR cascade in tumor cells, stromal expression of EGFR, and nuclear localization of COX-2 in metaplastic gland cells of laryngeal cancer tissue sample. Statistical analyses indicated that overexpression of the EGFR cascade is significantly correlated to cannabis smoking. Cannabis smokers had higher expression (p < 0.01) of these onco-proteins with respect to both nonsmokers as well as cigarette smokers. Risk factor analysis showed high risk of these proteins expression in age <60 years (odds ratio (OR) > 1.5) as the lower age group had relatively higher number of cannabis smokers. This study provides evidence for a direct association between cannabis smoking and increased risk of laryngeal cancer. Higher expression of the EGFR cascade in cannabis smokers revealed that cannabis smoking may be a major cause for the early onset of aggressive laryngeal cancer.

Outcomes of 3-year follow up with induction vs first line chemotherapy in oral cancer patients: An observational hospital-based study.

OBJECTIVE: Our study aims to analyse and compare the efficacy, adverse effect profile and survival among the Paclitaxel/Cisplatin/5-Flurouracil (TPF) induction chemotherapy and Paclitaxel/carboplatin (PC) first line or cisplatin chemotherapy in a high-volume tertiary care cancer centre. MATERIALS AND METHODS: 215 patients with oral cavity cancer were recruited in this study. Patients with stages I-IIc underwent surgical resection or radiation therapy 66-74 GY/fraction. Patients of Stages III-IV were administered with either induction chemotherapy TPF or PC or cisplatin regimen. Treatment responses were assessed by CT and MRI. Response rates, survival and adverse effects data were tabulated and analysed. RESULTS: The mean age was 49.2 ± 11.68 years. Symptoms were ulceration (33.5%), growth (20.5%), pain (13%), ulcer-proliferative growth (8.4%) and swelling (13, 6%). The tumour site was found at the base of the tongue, C01 (42.2%) followed by C06 (35.8%), C08 (6.5%), C07 (5.2%) and C05 (4.6%). There were no significant differences ( P > 0.05) in efficacy and survival outcomes between the different groups of treatment. Median survival was achieved within 36 months. The major side effect observed were anaemia (15.81%), diarrhoea (36.2%), dyspepsia (28.8%), fever (33.95%), mucositis (28.85%), myalgia (33.95%) and nausea (7.9%). Survival among the responder categories (CR, PR and NR) was significantly different as per Log-rank analysis ( P = 0.015). CONCLUSIONS: TPF induction therapy and PC first line chemotherapy showed similar efficacy, safety profile and survival whereas cisplatin shows poor efficacy and safety and survival in Indian oral cancer patients.

Clinical utility and prospective comparison of ultrasonography and computed tomography imaging in staging of neck metastases in head and neck squamous cell cancer in an Indian setup.

BACKGROUND: Preoperative lymph node screening of all neck compartments is favored by clinicians for the management of the neck. The presence of a metastatic node on one side of the neck reduces the 5-year survival rate to 50%, and the presence of a metastatic node on both sides of the neck reduces the 5-year survival rate to 25%. MATERIALS AND METHODS: This study compared the evaluation of lymph node metastases by ultrasonography (USG) and computed tomography (CT) in patients with squamous cell cancer of the head and neck region. RESULTS: Five hundred and eighty-four patients with squamous cell cancer of the head and neck were prospectively evaluated for the presence of cervical lymph node metastases. All patients underwent clinical examination (palpation), USG and CT imaging. Neck dissection was performed in all the patients, and the results of the preoperative evaluation were correlated with the surgical and histopathological findings. Metastases in neck nodes were identified in 148 patients by histopathological examination. Doppler USG correctly identified 136 node-positive patients (n = 148; sensitivity 91.8%, specificity 97%). CT imaging correctly identified 122 patients with metastatic lymph nodes (n = 148; sensitivity 83%, specificity 93%). Positive predictive values of USG and CT imaging were 95.6% and 91.3%, respectively, whereas the negative predictive values of these two imaging studies were 95.4% and 89.6%, respectively. CONCLUSIONS: The accuracy and sensitivity of USG in detection of cervical lymph node metastases make it a potentially promising and cheap preoperative tool for staging neck node metastases and optimizing the treatment plan for surgeons, especially in countries such as India.

Contrast CT Scan Evaluation of Incidence and Pattern of Thyroid Gland Involvement in Locally Advanced Ca Larynx Modifying the Need of Routine Thyroidectomy with Total Laryngectomy.

In locally advanced cases of carcinoma larynx, which are being treated with total laryngectomy, routine excision of the thyroid gland (either total or hemi section) is carried out. This study was carried out to evaluate the requirement of routine thyroidectomise with total laryngectomy. An analysis of the final histology of 83 patients, who underwent the traditional treatment, together with the preoperative contrast enhanced CT scan was carried out. Among 58 cases of T3 carcinoma larynx 2 revealed thyroid involvement by metastasis (3.45%), 1 of them was suspected in preoperative CT and confirmed by FNAC. Among 25 cases of T4a carcinoma larynx 6 revealed thyroid involvement by direct extension (24%) with evidence of same in preoperative CT. Risk of thyroid involvement is low in T3 cases (3.45%) and is by metastasis. Risk of thyroid involvement is higher in T4a cases (24%) and is by direct extension. Preoperative CECT is a good tool to predict thyroid gland involvement either by metastasis or by direct spread. This study thus raises doubts about the requirement of routine thyroidectomise in association with total laryngectomies in advanced carcinoma larynx. We thus believe that further investigations, on a larger scale and multi-institutional, is warranted.

CDKN2A-p53 mediated antitumor effect of Lupeol in head and neck cancer.

PURPOSE: The tumor suppressor protein p53 is known to control cell cycle arrest and apoptosis. Lupeol is a phytochemical that has been found to induce apoptosis in different cancer types through the extrinsic pathway. As yet, however, its role in the induction of cell cycle arrest and apoptosis through the intrinsic pathway in head and neck cancer has not been investigated. Here, we aimed at understanding the mechanism underlying the antitumor effect of Lupeol in head and neck cancer. METHODS: The antitumor effect of Lupeol on oral and laryngeal carcinomas was assessed using two in vitro 2D cell line models (HEp-2, UPCI:SCC-131) and, subsequently, an ex vivo 3D tumor explant culture platform that maintains key features of the native tumor microenvironment. The mechanism underlying Lupeol-mediated antitumor responses was delineated using MTT, colony formation, flow cytometry, immunofluorescence, Western blotting and immunohistochemistry assays. RESULTS: We found that Lupeol induced an enhanced expression of p53 in both cell line models tested and, subsequently, cell cycle arrest at the G1 phase. In addition we found that, following Lupeol treatment, p53 induced Bax expression and activated the intrinsic apoptotic pathway (as measured by Caspase-3 cleavage). Interestingly, Lupeol was also found to trigger G1 cell cycle arrest through up-regulation of the expression of CDKN2A, but not p21, resulting in inhibition of CyclinD1. In an ex vivo platform Lupeol was found to impart a potent antitumor response as defined by inhibition of Ki67 expression, decreased cell viability and concomitant activation (cleavage) of Caspase-3. Finally, we found that Lupeol can re-sensitize primary head and neck squamous cell carcinoma (HNSCC) tumor samples that had clinically progressed under a Cisplatin treatment regimen. CONCLUSION: Together, our data indicate that Lupeol may orchestrate a bifurcated regulation of neoplastic growth and apoptosis in head and neck cancers and may serve as a promising agent for the management of tumors that have progressed on a platinum-based treatment regimen.

Supraglottic laryngeal tumor microenvironmental factors facilitate STAT3 dependent pro-tumorigenic switch in tumor associated macrophages to render utmost immune evasion.

Content of tumor microenvironment (TME) is varied greatly among different types of laryngeal tumors, namely, supraglottic, glottic and subglottic tumors. These three different TMEs shape infiltrating monocytes/macrophages toward M2 genotypes in variable degrees. Results obtained from in vitro studies demonstrated extent of expression of M2 phenotypic features on macrophages was maximum after their exposure to supraglottic laryngeal tumor cell lysates (SLTCL) than glottic or subglottic lysates. Moreover, M2 macrophages generated under influence of SLTCL show less nitric oxide production, greater IL-10: IL-12 ratio and poor antigen presentation. Co-culture of such M2 macrophages with T cells from healthy donors resulted decreased activation of T cells and T cell mediated tumor cell cytotoxicity, than, glottic or subglottic. SLTCL mediated macrophage polarization is STAT3 dependent and might be one of the major factors for severe immune paralysis leading to poor prognosis of supraglottic laryngeal tumor bearer following standard treatment.

Dysregulated CC receptor/ligand in monocytes/macrophages from tongue squamous cell carcinoma patients is partially rectified by interferon α-2b.

In an aim to rectify dysregulated CC chemokine receptor (CCR5)/ligand (RANTES, MIP-1α, MIP-1ß) status of monocytes/macrophages in tongue squamous cell carcinoma (TSCC; n = 12) patients, we have tested interferon α2b (IFNα2b), a novel immunomodulator with wide use in the management of several forms of cancer. IFNα2b can upregulate reduced CCR5 expression and increases the suppressed secretory status of its ligands, as evidenced from in vitro studies on monocytes/macrophages from the peripheral blood of TSCC patients as well as healthy individuals. Isolated monocytes of TSCC patients (n = 5) undergoing chemotherapeutic treatment along with IFNα2b immunotherapy demonstrated significant upregulation in CCR5 expression and secretion of corresponding ligands. These rectifications in receptor/ligand levels are reflected in improved CCR5-dependent migration of monocytes/macrophages after IFNα2b treatment. The rectified chemokine profile and cellular migration translate into better tumoricidal and antigen-presenting functions of these cells. Accordingly, enhanced T-cell-mediated tumor cell killing is demonstrated upon IFNα2b treatment. Translating dual benefits on monocyte/macrophage functions, IFNα2b may emerge as a potential form of immunotherapy for TSCC patients that may be combined with standard chemotherapy for better clinical outcome.