Possible role of ALDH1 and CD44 in lip carcinogenesis.

BACKGROUND: Lip squamous cell carcinoma (LSCC) accounts for 12% of all head and neck cancers. It is caused by chronic exposure to ultraviolet light solar radiation and related to previous actinic cheilitis (AC). This study aimed to investigate the immunostaining of the putative cancer stem cells (CSC) markers ALDH1 and CD44 in AC (n=30) and LSCC (n=20). ALDH1 positivity was found to be statistically higher in LSCC than in AC lesions (p=0.0045), whilst CD44 expression was statistically higher in AC than in LSCC lesions (p=0.0155). ALDH1+ cells in AC lesions were associated with specific clinical features: a younger age (<60 years old), the female gender, white skin, not smoking or consuming alcohol, and a fast evolution, and not associated with the chronic exposure to UV radiation (p<0.0001). CD44 positivity was associated with patients who were male, feoderm, smoked, consumed alcohol, underwent occupational exposure to UV-radiation, and demonstrated lesions with log-time evolution (p<0.0001). ALDH1 + cells were associated with mild dysplasia using a system from the World Health Organization (WHO), and with a low risk of malignant transformation, according to the binary system (p<0.0001). CD44+ cells were also associated with moderated dysplasia, according to the WHO system. In LSCC, ALDH1 + cells were positively associated with patients who were older (≥ 60 years old), smokers, and with those who consumed alcohol (p<0.0001). CD44 + cells in LSCC were associated with older (≥ 60 years old) patients as well, but also with female patients, white skin, non-smokers, and individuals who did not consume alcohol (p<0.0001), all of whom showed distinct patterns in pre- and malignant lesions of both markers. Additionally, in LSCC, both ALDH1 and CD44 staining were associated with smaller tumor sizes (T1/T2; p<0.0001). In summary, although both ALDH1 and CD44 were associated with the presence of dysplasia in AC lesions, the present findings suggest that ALDH1 and CD44 may be activated by different etiopathogenic pathways, predominantly in distinct steps of oral carcinogenesis. CD44 would thus be more significantly related to the potentially malignant lesion, while ALDH1 would be closely linked to malignancy.

Anti-PD-1 immunotherapy with dose-adjusted ultra-hypofractionated re-irradiation in patients with locoregionally recurrent head and neck cancer.

INTRODUCTION: Patients with recurrent inoperable squamous-cell head-neck cancer (HNSCC) after chemo-radiotherapy have an ominous prognosis. Re-irradiation can be applied with some efficacy and high toxicity rates. Anti-PD-1 immunotherapy is effective in 25% of patients. Immunogenic death produced by large radiotherapy (RT) fractions may enhance immune response. MATERIALS AND METHODS: We evaluated the efficacy and tolerance of ultra-hypofractionated immuno-radiotherapy (uhypo-IRT) in 17 patients with recurrent HNSCC and 1 with melanoma. Four of HNSCC patients also had oligometastatic disease. Using a dose/time/toxicity-based algorithm, 7, 7 and 4 patients received 1, 2 and 3 fractions of 8 Gy to the tumor, respectively. Nivolumab anti-PD-1 immunotherapy was administered concurrently with RT and continued for 24 cycles, or until disease progression or manifestation of immune-related adverse events (irAEs). RESULTS: Early and late RT toxicities were minimal. Three patients developed irAEs (16%). After the 12th cycle, 7/17 (41.2%) and 5/17 (29.4%) patients with HNSCC showed complete (CR) and partial response (PR), respectively. CR was also achieved in the melanoma patient. The objective response rates in HNSCC patients were 57%, 86% and 66%, after 1, 2 and 3 fractions, respectively (overall response rate 70.6%). Most responders experienced an increase in peripheral lymphocyte counts. The median time to progression was 10 months. The 3-year projected locoregional progression-free survival was 35%, while the 3-year disease-specific overall survival was 50%. CONCLUSIONS: Anti-PD1 uhypo-IRT is safe and effective in patients with recurrent HNSCC. The high objective response rates and the long survival without evidence of disease support further trials on uhypo-IRT.

Effect of low-level light therapy before radiotherapy in oral squamous cell carcinoma: An in vitro study.

Radiation therapy for head and neck squamous cell carcinoma (HNSCC) is associated with several complications. Although photobiomodulation (PBM) has radioprotective effects in normal tissue, it could also enhance the growth of neoplastic cells. Thus, the present study aimed to investigate the cellular response of oral squamous cell carcinoma with pre-exposure to low-level phototherapy before radiotherapy. SCC9, Cal-27, A431, and HaCaT cell lines were subjected to low-level light therapy and radiotherapy. The cells were treated with a single energy density (300 J/cm2) of a light-emitting diode (660 nm) prior to ionizing radiation at different doses (0, 2, 4, and 6 Gy). After 24 h, wound scratch, proliferation, clonogenic cell survival, cell death, and reactive oxygen species (ROS) analyses were performed to evaluate cell response. The cell lines pre-exposed to PBM at the analyzed dosage were radiosensitive. The treatment significantly reduced cell proliferation and clonogenic cell survival. Migration and cell death assays also revealed positive results, with the treatment group showing lower rate of migration and higher cell death than did the control group. Moreover, PBM effectively increased the intracellular levels of ROS. PBM at 300 J/cm2 is a promising radiosensitizing modality to reduce the radiation dose and avoid the intolerable side effects of radiotherapy for HNSCC, thus increasing the probability of successful treatment. However, further studies are needed to support and confirm the results.

Photodynamic therapy for squamous cell carcinoma of the head and neck: narrative review focusing on photosensitizers.

This narrative review aimed to evaluate the effectiveness of PDT in early or advanced squamous cell carcinoma of the head and neck (SCCHN). Scopus, MEDLINE/PubMed, and Embase were searched electronically following the PRISMA protocol. Quality assessment was performed according to JBI, NIH, and AMSTAR protocols. The main outcomes evaluated were treatment response, recurrence, survival, and adverse effects. A total of 49 articles met the search criteria: 43 case series, two cohort studies, two prospective before-after clinical trials, one systematic review, and one meta-analysis. Data from 2121 SCCHN patients were included. The response to PDT was variable according to the type of photosensitizer, tumor location, and tumor stage. In general, higher complete responses rated were observed in T1/T2 SCCHN, mainly with mTHPC-mediated PDT. With regard to T3/T4 or advanced SCCHN tumors, there is no compelling evidence suggesting the effectiveness of PDT. Any adverse effects reported were well tolerated by patients. The present review suggests that PDT is a promising treatment modality for early-stage SCCHN. Although there are limitations due to the low level of evidence of the included studies, we believe that the present review could help to design robust clinical trials to determine the efficacy of PDT in SCCHN.

Head and neck cancer risk factors in the French West Indies.

OBJECTIVES: The incidence of head and neck squamous cell carcinoma (HNSCC) in the French West Indies (FWI) is relatively high, despite a low prevalence of tobacco smoking and alcohol drinking. Little is known about other risk factors in the FWI. We assessed associations between several factors and HNSCC risk, their population attributable fractions (PAF) in the FWI, and compared these PAFs by subsite, sex and age. MATERIALS AND METHODS: We conducted a population-based case-control study (145 cases and 405 controls). We used logistic regression models to estimate adjusted odds-ratios (OR), PAFs and their 95% confidence intervals (CI). RESULTS: Tobacco smoking, alcohol drinking, high-risk HPV, family history of HNC, low BMI and several occupations and industries were significantly associated to the occurrence of HNSCC. The majority of HNSCC cases were attributable to tobacco smoking (65.7%) and alcohol (44.3%). The PAF for the combined consumption of tobacco and/or alcohol was 78.2% and was considerably larger in men (85%) than in women (33%). The PAFs for the remaining risk factors were 9% for family history of HNSCC, 9% for low BMI, 15% for high-risk HPV, and 25% for occupations. The overall PAF for all risk factors combined was 89.0% (95% CI = 82.0-93.2). The combined PAFs by sex were significantly greater in men (93.4%, 95% CI = 87.5-96.5) than in women (56.4%, 95% CI = 18.7-76.6). CONCLUSION: Tobacco and alcohol appeared to have the greatest impact on HNSCC incidence among the studied risk factors, especially among men. Prevention programs for HNSCC in the FWI should target tobacco and alcohol cessation, particularly in men. Future research should emphasise on the role of occupational factors to better understand this disease.

Expression levels of SCCA and CYFRA 21-1 in serum of patients with laryngeal squamous cell carcinoma and their correlation with tumorigenesis and progression.

PURPOSE: To explore the concentration of squamous cell carcinoma antigen (SCCA), cytokeratin fragment antigen 21-1 (CYFRA21-1) in patients with laryngeal squamous cell carcinoma (LSCC) and its correlation with tumorigenesis and progression. METHODS: A total of 78 patients with LSCC admitted to our hospital from February 2010 to January 2016 were enrolled as the research group (RG), and another 41 healthy volunteers from the same period were selected as the control group (CG). The serum concentrations of SCCA and CYFRA21-1 in patients with LSCC were detected by ELISA, whose diagnostic value in LSCC were further analyzed by ROC curve. The prognosis and survival curves of patients with LSCC were observed according to the median value of serum SCCA and CYFRA21-1 concentrations. RESULTS: The concentration of CYFRA21-1 and SCCA in the RG was significantly higher than that in the CG (p < 0.050). The SCCA and CYFRA21-1 identified a significant difference in smoking, lymphatic metastasis, TNM staging, and differentiation degree (p < 0.050). The survival rate of the SCCA low-concentration group was significantly better than that of the high-concentration group, p < 0.050. The survival rate of the CYFRA21-1 low-concentration group was markedly better than that of the high-concentration group, p < 0.050. CONCLUSIONS: SCCA and CYFRA21-1 are highly concentrated in LSCC patients, which have good diagnostic efficacy for LSCC. In addition, they play some certain role in the occurrence and development of LSCC, and are expected to be markers for early diagnosis and prognosis of this disease.

Consumption of minimally processed foods as protective factors in the genesis of squamous cell carcinoma of the head and neck in Brazil.

BACKGROUND: Head and neck cancer (HNC) is the sixth most common cancer, and two-fifths of cases could be avoided by changing lifestyle and eating habits. METHODS: This multicenter case-control study was conducted under the International Consortium on Head and Neck Cancer and Genetic Epidemiology, coordinated by the International Agency for Research on Cancer. This consortium evaluated associations between minimally processed food consumption and the risk of HNC in three Brazilian states. RESULTS: We evaluated 1740 subjects (847 cases and 893 controls). In multiple analyses including recognized risk factors for HNC, the consumption of apples and pears was associated with reduced risks of oral cavity and laryngeal cancers; the consumption of citrus fruits and fresh tomatoes was associated with a reduced risk of oral cavity cancer; the consumption of bananas was associated with a reduced risk of oropharynx cancer; the consumption of broccoli, cabbage, and collard greens was associated with reduced risks of laryngeal and hypopharyngeal cancers; and the consumption of carrots and fresh fruits was associated with a reduced risk of hypopharyngeal cancer. CONCLUSIONS: The consumption of a heathy diet rich in fruits and vegetables was associated with a reduced risk of HNC. Public policies, including government subsidies, are essential to facilitate logistical and financial access to minimally processed foods, thereby strengthening environments that promote healthy behavior.

Prevalence of hepatitis C virus infection and its impact on the prognosis of head and neck cancer patients.

OBJECTIVE: Several studies have shown a higher prevalence of hepatitis C virus (HCV) infection among patients with head and neck cancer (HNC) compared to the general population. In Brazil, the prevalence of HCV infection is considered low (1.38%). The aim of this study was to determine HCV prevalence and how this can modify outcomes of patients with HNC. STUDY DESIGN: Retrospective cohort. METHODS: Patients with a diagnosis of malignant neoplasm in the head and neck (HN) region and who had serology performed for HCV were included. Patients were classified into two groups: head and neck squamous cell carcinoma (HNSCC) and other head and neck malignant neoplasms (OHNMN). Descriptive statistics were performed for all variables of interest. Means were compared using ANOVA and proportions using chi-square tests. Survival data were compared by Kaplan-Meier curves and log-rank test. RESULTS: Global HCV prevalence in patients with HNC was 7.8%, reaching 12.8% in HNSCC and 3.4% in OHNMN (p = 0.003). There was a higher risk of developing a second primary neoplasm in HNSCC compared to OHNMN patients (20.6% versus 4.6%; p = 0.001). The mean survival was not different between HCV-positive and HCV-negative patients (6.0 years versus 6.6 years, respectively, p = 0.516). CONCLUSION: The prevalence of HCV infection was higher in HNC patients compared to the general Brazilian population. It seems reasonable to consider that HCV infection is associated with an increased risk of HNC, but HCV infection does not worsens the prognosis of HNC patients.