Age at menopause and hormone replacement therapy as risk factors for head and neck and oesophageal cancer (Review).

There were ~986,000 cases of head and neck cancer (HNC) and oesophageal cancer diagnosed worldwide in 2012. The incidence of these types of cancer is much higher in males than females, although this disparity decreases in the elderly population, suggesting a role for hormones as a risk factor. This systematic review investigates the potential role of female hormones [age at menopause and use of hormone replacement therapy (HRT)] as risk factors for HNC/oesophageal squamous cell carcinoma (SCC). The electronic databases MEDLINE, Web of Science, EMBASE and Cochrane were searched. Only studies with at least 50 cases of HNC/oesophageal SCC, with data on age at menopause, smoking, alcohol, age and socioeconomic status or educational attainment, were included. The Newcastle Ottawa Scale was used for assessing risk of bias. Eight studies met the inclusion criteria (5 oesophageal SCC, 2 HNC and 1 combined oesophageal SCC and HNC). HRT was shown to reduce the risk of HNC (HR, 0.78; 95% CI, 0.61-0.99) in one study. Our results showed that earlier age at menopause is a risk factor for oesophageal SCC, with women entering menopause at <45 years having double the risk of those entering menopause at age >50 years. Similar, but less striking, results were observed for HNC. HRT was found to reduce the risk of HNC/oesophageal SCC, but the evidence is inconclusive. We, therefore, recommend that consideration should be given to collecting data on reproductive factors and exposure to HRT, as routine practice, in future epidemiological and clinical studies of these cancers. The concept of oestrogen deficiency as a risk for HNC/oesophageal SCC deserves further exploration in future laboratory and clinical studies.

Management of proliferative verrucous leukoplakia: Justification for a conservative approach.

BACKGROUND: Proliferative verrucous leukoplakia (PVL) is a progressive, multifocal, exophytic form of leukoplakia with high rates of malignant transformation. The purpose of this study was to evaluate a cohort of patients with PVL in a single tertiary referral clinic. METHOD: Cases meeting accepted diagnostic criteria were reviewed with regard to their pathology, demographic characteristics, management, and outcomes. Human papillomavirus (HPV) testing was undertaken on a subset. RESULTS: Almost half of the 48 patients with PVL (48%; n = 23) underwent malignant transformation after a median 23.4 months. The characteristics of this cohort were similar to those previously described, but management was notably more conservative. Conservative management of PVL was used in 92% of our patients, but the clinical outcomes seem comparable with previously described cohorts in which PVL was predominantly treated by surgical excision. All HPV testing was negative. CONCLUSION: Aggressive surgical intervention in the premalignant phase of PVL may not influence the rate of malignant transformation.

DNA damage marker phosphorylated histone H2AX is a potential predictive marker for progression of epithelial dysplasia of the oral cavity.

AIMS: To evaluate the relationships between immunohistochemical markers related to cellular senescence, cell proliferation and histological grade of epithelial dysplasia (OD) of the oral cavity. In addition, the predictive value of these markers for progression of OD was assessed. METHODS AND RESULTS: Retrospective immunohistochemical analyses were performed on 86 formalin-fixed paraffin-embedded specimens of OD and oral squamous cell carcinoma (OSCC) for Ki67, phosphorylated histone H2AX (γH2AX), p53, p16, trimethyl-histone H3 (Lys9) (H3K9me3) and cyclin D1 (CycD1). Three separate areas representing the highest severity of OD on each slide were annotated digitally by two independent pathologists. Mean automated histoscores of the selected markers were generated and compared to that of age-matched healthy controls (n = 24). Follow-up data of OD were retrieved and anonymized by a clinical team member and linked using unique participant identifiers. The median follow-up was 10.9 years (interquartile range: 10.1-11.5). Ki67 (P < 0.0001), γH2AX (P = 0.03) and p53 (P = 0.04) were increased significantly with higher histological grade of OD. γH2AX (P = 0.03), but not histological grade of OD (P = 0.73), was associated prospectively with disease progression. Using the median histoscore for γH2AX (median histoscore = 17) as a cut-off, histoscore ≥17 was associated with an increased risk of disease progression [hazard ratio (HR) = 3.15, 95% confidence interval (CI): 1.41-7.39, P = 0.0064]. CONCLUSIONS: Although proliferation marker Ki67, DNA damage/checkpoint markers γH2AX and p53 were increased in higher grade of OD, only γH2AX was predictive of disease progression. These observations may reflect the role of DNA replicative stress in the transformation from OD to OSCC. Larger studies should evaluate whether γH2AX can be used as a predictive marker of OD.

Trends and regional variation in the incidence of head and neck cancers in England: 2002 to 2011.

Recent studies show an increased incidence of head and neck cancers worldwide. The present study evaluated the trend in the incidence of head and neck cancers in England during 2002-2011. Data were extracted from the database of Office for National Statistics. The study population was categorised according to age, residential area, gender and cancer sub-types. Overall trend in incidence of head and neck cancer and some subtypes were examined using Poisson regression models. In total, 71,457 head and neck cancers were registered in England between 2002 and 2011 and 68% of patients were males. Statistically significant increases in incidence of 27.0 and 32.4% were documented in males and females, respectively (p<0.001) with the largest increase in the 60+ age category. Potentially HPV-associated cancers, oral cavity cancers and laryngeal cancers increased by 47.1, 24.1 and 1.7% in males and 37.5, 25.5 and 7.7% in females, respectively (p<0.001). Regional differences were also noted with the highest incidence (18.0 and 17.0 per 100,000, respectively) in the North East and North West of England. Our results for England showed an increase in the incidence of both oral cavity and oropharyngeal cancer in both genders, whilst laryngeal cancer incidence remained stable.