Eighty patients affected by supraglottic cancer were treated by transoral carbon dioxide laser surgery between 1989 and 2006 in two Italian institutions. Patient staging was as follows: 2 pTis, 20 ...pT1, 38 pT2, and 20 pT3. Simultaneous or 1-month delayed neck dissection (ND) was performed on 27 (34%) patients, unilaterally in 10 and bilaterally in 17. The pN category was as follows: 9 pN0, 6 pN1, 8 pN2b, and 4 pN2c. A total of 16 (20%) patients received complementary radiotherapy (RT) and 5 (6%) were subjected to chemo-RT for persistent tumor after re-excision due to positive margins, multiple lymph nodes, and/or extracapsular spread after ND. The last follow-up was in December 2008. The 5-year overall, disease-specific and disease-free survivals, local control with laser alone, and organ preservation rates calculated by Kaplan–Meier analysis were 84.4, 97.4, 88.3, 96, and 97.2%, respectively. Univariate analysis showed a statistically significant impact on disease-free survival, local control with laser alone, and organ preservation of pT category (
p
= 0.009,
p
= 0.01, and
p
= 0.03, respectively), while pN category and tumor stage negatively influenced disease-free survival (
p
= 0.007 and
p
= 0.01, respectively). This series confirms the good overall oncologic outcomes obtained by transoral laser surgery for Tis, T1, T2, and selected T3 supraglottic cancer with minimal pre-epiglottic space involvement.
Medullary thyroid carcinoma (MTC) can assume various cytomorphological and architectural forms, mimicking other thyroid and extra-thyroid tumors and rendering the cytological and histological ...diagnosis challenging. Consequently, measurement of calcitonin (CT) levels is generally considered to be more accurate than cytology in diagnosing MTC. Here, we report on a patient with a multinodular goiter and significantly elevated basal CT levels; based on cytology examination and CT immunocytostains, neither MTC nor C-cell hyperplasia was detected upon final histopathological examination. CT testing has a high false-positive rate and low positive predictive value for detecting clinically relevant MTC. Judicious integration of cytological examination with immunocytochemical stains (when needed) may be useful for selecting the most appropriate therapy and avoiding overtreatment (i.e., central neck lymph node dissection in the present case). This case demonstrates that cytological examination with ancillary techniques is still valuable in patients with thyroid nodules and suspicious MTC.
The main risk factors for head and neck cancer (HNC) are tobacco and alcohol use. However, an important fraction of oropharyngeal cancer (OPC) is caused by human papillomaviruses (HPV), a subgroup ...with increasing incidence in several western countries.
As part of the HPV-AHEAD study, we assessed the role of HPV infection in 772 archived tissue specimens of Belgian HNC patients: 455 laryngeal (LC), 106 oral cavity (OCC), 99 OPC, 76 hypopharyngeal (HC), and 36 unspecified parts of the head and neck. All specimens were tested for HPV DNA (21 genotypes); whereof all HPV DNA-positives, all HPV DNA-negative OPCs and a random subset of HPV DNA-negatives of the other HNC-sites were tested for the presence of type-specific HPV RNA and p16
over-expression.
The highest HPV DNA prevalence was observed in OPC (36.4 %), and was significantly lower (p < 0.001) in the other HNCs (OCC:7.5 %, LC:6.6 %). HPV16 was the most common HPV-genotype in all HNCs. Approximately 83.0 % of the HPV DNA-positive OPCs tested HPV RNA or p16-positive, compared to about 37.5 % and 44.0 % in OCC and LC, respectively. Estimation of the attributable fraction of an HPV infection in HNC was very similar for HPV RNA or p16 in addition to DNA-positivity; with 30 % for OPC, and 3 % for OCC and LC.
Our study confirms the heterogeneity of HPV DNA prevalence across anatomical sites in HNC, with a predominance of HPV16 in all sites. The estimated proportion of HPV-driven HNC in Belgium, during the period 1980-2014, was 10 times higher in OPC compared to OCC and LC.
Abstract Our aim was to analyse the overall and disease-free survival (DFS), time to recovery of oral feeding, and morbidity, in a consecutive series of patients who had total glossectomy with ...preservation of the larynx for advanced cancer of the tongue at the European institute of Oncology (Milan). From June 2002 to April 2011, 37 patients who were treated for advanced cancer of the tongue had total glossectomy, bilateral neck dissection, and preservation of the larynx. Various flaps were used for reconstruction. Overall and disease-free survival were assessed from the day of operation to the latest outpatient examination. Postoperative morbidity and rehabilitation of feeding were also assessed. Six patients had major complications, four of whom had a second operation for necrosis of the flap. Actuarial five-year overall survival (OS) and disease-free survival were 54% and 47%. Twenty-four patients (65%) were operated on as their first treatment, and had 79% five-year overall survival and 61% 5-year disease-free survival. Twenty-six patients were eventually able to feed orally postoperatively. Although this retrospective study include a limited number of patients, the results support the validity of total glossectomy as a safe procedure for advanced cancer of the tongue. Pretreated patient were previously treated with surgery, radiotherapy or chemoradiotherapy with curative purposes. Nevertheless, the long period required for recovery of oral feeding indicates that total glossectomy should be reserved for highly motivated patients.
The DOK1 gene is a putative tumour suppressor gene located on the human chromosome 2p13 which is frequently rearranged in leukaemia and other human tumours. We previously reported that the DOK1 gene ...can be mutated and its expression down‐regulated in human malignancies. However, the mechanism underlying DOK1 silencing remains largely unknown. We show here that unscheduled silencing of DOK1 expression through aberrant hypermethylation is a frequent event in a variety of human malignancies. DOK1 was found to be silenced in nine head and neck cancer (HNC) cell lines studied and DOK1 CpG hypermethylation correlated with loss of gene expression in these cells. DOK1 expression could be restored via demethylating treatment using 5‐aza‐2′deoxycytidine. In addition, transduction of cancer cell lines with DOK1 impaired their proliferation, consistent with the critical role of epigenetic silencing of DOK1 in the development and maintenance of malignant cells. We further observed that DOK1 hypermethylation occurs frequently in a variety of primary human neoplasm including solid tumours (93% in HNC, 81% in lung cancer) and haematopoietic malignancy (64% in Burkitt's lymphoma). Control blood samples and exfoliated mouth epithelial cells from healthy individuals showed a low level of DOK1 methylation, suggesting that DOK1 hypermethylation is a tumour specific event. Finally, an inverse correlation was observed between the level of DOK1 gene methylation and its expression in tumour and adjacent non tumour tissues. Thus, hypermethylation of DOK1 is a potentially critical event in human carcinogenesis, and may be a potential cancer biomarker and an attractive target for epigenetic‐based therapy.
Only limited data is available on the relationship between family history of laryngeal and other neoplasms and laryngeal cancer risk. We investigated the issue using data from a multicentre ...case‐control study conducted in Italy and Switzerland between 1992 and 2009 including 852 cases with histologically confirmed laryngeal cancer and 1970 controls admitted to hospital for acute, non neoplastic conditions. Unconditional logistic regression models adjusted for age, sex, study center, education, tobacco smoking, alcohol drinking and number of siblings were used to estimate the odds ratios (ORs) of laryngeal cancer. The multivariate OR was 2.8 (95% confidence interval CI, 1.5–5.3) in subjects reporting a first‐degree relative with laryngeal cancer, as compared to subjects with no family history. The OR was higher when the relative was diagnosed before 60 years of age (OR = 3.5, 95% CI 1.4–8.8). As compared to subjects without family history, non‐smokers, and moderate drinkers, the OR was 37.1 (95% CI 9.9–139.4) for current smokers, heavy drinkers, with family history of laryngeal cancer. Family history of colorectal (OR = 1.5, 95% CI 1.0–2.3) and kidney (OR = 3.8, 95% CI 1.2–12.1) cancer were also associated to an increased risk of laryngeal cancer, while no significant increase in risk was found for family history of cancer at all sites, excluding the larynx (OR = 1.1).
Abstract HNC is the 11th most frequent carcinoma with a world-wide yearly incidence exceeding over half a million cases 1 , a 10:1 male gender predilection and country specific variability 2 . The ...principal risk factors are tobacco and alcohol use and, in a growing population without these exposures, HPV infection. While much progress has been made in understanding the molecular basis of cancer, the 5-year mortality of head and neck cancer has remained approximately 50%. To this date we have not been able to translate as much of our basic science knowledge into significant disease altering therapeutic strategies in terms of local, loco-regional, functional and overall survival. Challenges remain in all aspects of head and neck cancer management: prevention, diagnosis, surgical and non-surgical treatment.