HPV Status Improves Classification of Head and Neck Gray Zone Cancers.

In epidemiologic studies, patients with head and neck squamous cell carcinoma (HNSCC) are classified mainly by the International Classification of Diseases (ICD) codes. However, some patients are of an unclear subsite, the "gray zone" cases, which could reflect ICD coding error, absence of primary subsite, or extensive primary tumors that cross over multiple subsites of the oral cavity and oropharynx. Patients with gray zone squamous cell carcinomas were compared with patients with oral cavity squamous cell carcinoma (OSCC) or oropharyngeal squamous cell carcinoma (OPSCC) and stratified by human papillomavirus (HPV) status that was determined by p16 immunostaining or HPV serology. Comparisons consisted of clinicodemographic features and prognostic outcomes presented by Kaplan-Meier curves and Cox proportional hazards regression models, reported as hazard ratios. There were 158 consecutive patients with gray zone HNSCC diagnosed at the Princess Margaret Cancer Center between 2006 and 2017: 66 had subsite coding discrepancies against the clinician's documentation ("discrepant" cases; e.g., the diagnosis by the clinician was OSCC, while the classification by ICD coding was OPSCC), while 92 were squamous cell carcinoma of unknown primary of the head and neck (SCCUPHN) after complete diagnostic workup. Comparators included 721 consecutive OSCC and 938 OPSCC adult cases. All HPV-positive cohorts (OPSCC, discrepant, and SCCUPHN) had similar clinicodemographic characteristics and better 3- and 5-y overall survival and disease-free survival than their HPV-negative counterparts. In contrast, HPV-negative discrepant cases had prognostic outcomes most similar to HPV-negative OPSCC cases, while HPV-negative SCCUPHN had survival outcomes most similar to those of patients with OSCC in this study. HPV-positive status can improve the classification of patients with unclear or discrepant oral/oropharyngeal subsite, an improvement over classification systems that are solely clinician defined or conducted through ICD coding. However, due to clinical practice, we could not make definitive reclassification for patients with HPV-negative gray zone HNSCC.

Socioeconomic status, human papillomavirus, and overall survival in head and neck squamous cell carcinomas in Toronto, Canada.

BACKGROUND: Despite universal healthcare in some countries, lower socioeconomic status (SES) has been associated with worse cancer survival. The influence of SES on head and neck cancer (HNC) survival is of immense interest, since SES is associated with the risk and prognostic factors associated with this disease. PATIENTS AND METHODS: Newly diagnosed HNC patients from 2003 to 2010 (n=2124) were identified at Toronto's Princess Margaret Cancer Centre. Principal component analysis was used to calculate a composite score using neighbourhood-level SES variables obtained from the 2006 Canada Census. Associations of SES with overall survival were evaluated in HNC subsets and by p16 status (surrogate for human papillomavirus). RESULTS: SES score was higher for oral cavity (n=423) and p16-positive oropharyngeal cancer (OPC, n=404) patients compared with other disease sites. Lower SES was associated with worse survival [HR 1.14 (1.06-1.22), p=0.0002], larger tumor staging (p<0.001), current smoking (p<0.0001), heavier alcohol consumption (p<0.0001), and greater comorbidity (p<0.0002), but not with treatment regimen (p>0.20). After adjusting for age, sex, and stage, the lowest SES quintile was associated with the worst survival only for OPC patients [HR 1.66 (1.09-2.53), n=832], primarily in the p16-negative subset [HR 1.63 (0.96-2.79)]. The predictive ability of the prognostic models improved when smoking/alcohol was added to the model (c-index 0.71 vs. 0.69), but addition of SES did not (c-index 0.69). CONCLUSION: SES was associated with survival, but this effect was lost after accounting for other factors (age, sex, TNM stage, smoking/alcohol). Lower SES was associated with greater smoking, alcohol consumption, comorbidity, and stage.

Two novel BRM insertion promoter sequence variants are associated with loss of BRM expression and lung cancer risk.

SWI/SNF (SWItch/sucrose non-fermentable) complexes are ATP-dependent chromatin remodeling enzymes critically involved in the regulation of multiple functions, including gene expression, differentiation, development, DNA repair, cell adhesion and cell cycle control. BRM, a key SWI/SNF complex subunit, is silenced in 15-20% of many solid tumors. As BRM-deficient mice develop 10-fold more tumors when exposed to carcinogens, BRM is a strong candidate for a cancer susceptibility gene. In this paper, we show that BRM is regulated by transcription, thus demonstrating that the promoter region is important for BRM expression. We sequenced the BRM promoter region, finding two novel promoter indel polymorphisms, BRM -741 and BRM -1321, that are in linkage disequilibrium (D'≥0.83). The variant insertion alleles of both polymorphisms produce sequence variants that are highly homologous to myocyte enhancer factor-2 (MEF2) transcription factor-binding sites; MEF2 is known to recruit histone deacetylases that silence BRM expression. Each polymorphic BRM insertion variant is found in ~20% of Caucasians, and each correlates strongly with the loss of protein expression of BRM, both in cancer cell lines (P=0.009) and in primary human lung tumor specimens (P=0.015). With such strong functional evidence, we conducted a case-control study of 1199 smokers. We found an increased risk of lung cancer when both BRM homozygous promoter insertion variants were present: adjusted odds ratio of 2.19 (95% confidence interval, 1.40-3.43). Thus, we here demonstrate a strong functional association between these polymorphisms and loss of BRM expression. These polymorphisms thus have the potential to identify a sub-population of smokers at greater lung cancer risk, wherein this risk could be driven by an aberrant SWI/SNF chromatin-remodeling pathway.

Cryotherapy in the treatment of pyogenic granuloma.

BACKGROUND: Pyogenic granuloma is a benign, acquired, proliferative vascular lesion of the skin and mucous membranes. Many different treatments have been used for pyogenic granuloma with variable success rates. OBJECTIVE: To evaluate the efficacy of cryotherapy in the treatment of pyogenic granuloma. METHODS: In a prospective observational study, 135 patients with pyogenic granuloma were treated with cryotherapy using liquid nitrogen. The patients were followed up every 3 weeks until 3 months after disappearance of the lesion. RESULTS: Complete resolution of the pyogenic granuloma was achieved in all patients after a mean of 1.58 treatments (range, 1-4 treatments). At the end of follow-up period, there was a flat imperceptible scar, smaller than the treated lesion, in 16 patients (11.8%). A hypertrophic scar, 3 mm in diameter, was observed in one patient. Hypopigmentation was observed in seven patients (5.1%). No other complication or side-effect was recorded in the study. CONCLUSIONS: We believe that pyogenic granuloma can be treated simply and effectively with cryotherapy.

Photodynamic therapy as a new treatment of cutaneous leishmaniasis.

We assessed the effectiveness of photodynamic therapy in the treatment of cutaneous leishmaniasis in 5 patients. Delta-aminolevulinic acid in a water-in-oil emulsion was applied to the lesions and irradiation was performed. The treatment was repeated once a week for a month. Each time, direct smears of the lesions were prepared and cultured in NNN media. In direct staining, smears showed no amastigotes after 1 or 2 sessions. Healing and cosmetic outcome after photodynamic therapy was excellent. Only mild local inflammatory reaction was noted with no scarring and 4 months after the last treatment session, there were no clinical signs of recurrence.

Photodynamic therapy as a new treatment of cutaneous leishmaniasis

We assessed the effectiveness of photodynamic therapy in the treatment of cutaneous leishmaniasis in 5 patients. Delta-aminolevulinic acid in a water- in-oil emulsion was applied to the lesions and irradiation was performed. The treatment was repeated once a week for a month. Each time, direct smears of the lesions were prepared and cultured in NNN media. In direct staining, smears showed no amastigotes after 1 or 2 sessions. Healing and cosmetic outcome after photodynamic therapy was excellent. Only mild local inflammatory reaction was noted with no scarring and 4 months after the last treatment session, there were no clinical signs of recurrence