The significance of p16 protein expression in oral squamous cell carcinoma.

INTRODUCTION: Human papillomavirus (HPV) infection plays an important role in the etiopathogenesis of oropharyngeal squamous cell carcinomas. HPV detection in these tumours is a positive prognostic marker. The p16 protein expression, which is detected immunohistochemically, is an indirect marker of active HPV infection. Unlike in oropharyngeal carcinoma, in oral carcinoma, the prognostic significance of HPV/p16 positivity is unclear. Some studies even show a worse prognosis in patients with HPV/p16 positive oral carcinoma. The aim of our study is to consider the significance of p16 protein expression in relation to clinicopathological parameters and prognosis in patients with oral squamous cell carcinomas.  Methods: One hundred and twenty patients treated surgically for oral carcinoma were enrolled in the study. The most common anatomical sites of oral carcinoma were the tongue body (54; 45% of cases) and floor of mouth (35; 29.2% of cases). All tumours were analysed immunohistochemically for p16 protein expression. The results were correlated with the clinicopathological parameters and analysed statistically. RESULTS: Ten patients (8.3%) tested positive for p16 expression. In the study cohort, p16 expression was identified as the most significant factor with a negative effect on survival (p=0.019). Based on the Cox proportional hazard model, the p16-positive patients had four times worse survival than the p16-negative ones. Other factors with a statistically significant effect on survival were T status, N status, and recurrence. CONCLUSION: The significance of p16 expression differs between oral and oropharyngeal carcinomas. The p16 positivity seems to be a negative prognostic factor in oral carcinomas. Nevertheless, the significance of HPV presence in tumours outside the oropharyngeal area remains unclear.

Mucosal and skin HPV types in tumour-free tonsils and tonsillar tumours.

Human papillomavirus (HPV) infection is associated with tonsillar cancer (TC) whose incidence in humans is increasing. Tonsillar tumours are not ordinarily preceded by clinically apparent precancerous lesions, and no markers of the early stage disease are available. Therefore, we evaluated the presence of an active HPV infection also in tumour-free tonsillar tissue. Formalin-fixed paraffin-embedded (FFPE) tonsillar specimens from 114 patients with TC and 114 age and gender matched controls were screened for the presence of HPV DNA, expression of HR-HPV E6 mRNA, and p16 overexpression. HPV DNA was identified in 3.5% of tumour-free tissues, HR-HPV16 and 58 and LR-HPV111 and 17 were each detected in a single sample. No HR HPV E6 mRNA and p16 overexpression was found. The prevalence of HPV DNA in TC was 69.3%, with HPV16 being the most common (94.9%). Eighty-four percent of HPV16-positive tumours expressed HR HPV E6 mRNA, while no E6 mRNA was present in samples positive for HPV52 and 58. The overexpression of p16 correlated well with HPV DNA in TC, but in tumour-free tonsils no overexpression of p16 was detected.Our data provide further evidence of the etiological role of HPV16 in TC. In tumour-free tissue, the presence of HR-HPVs was rare and silent, as shown by direct and indirect markers.

The prevalence of oral HPV infection in healthy populations: A systematic review with a focus on European populations.

BACKGROUND: Human papillomaviruses (HPV), a group of small, tumorigenic DNA viruses, are causally linked to cervical cancer and various other anogenital, oral, and oropharyngeal malignancies in both males and females. The purpose of this systematic review is to summarize the most recent data on the prevalence of oral HPV in healthy populations in Europe. METHODS: A systematic review of the European studies on the prevalence of oral HPV infections published from January 2011 to September 2017. RESULTS: The overall prevalence rates of oral HPV in healthy populations vary between 1.2% and 11.6%, with high-risk types of HPV (HR HPV) detected in 2.2% to 7.2% of individuals and HPV16 in 0.2% to 2.9% of individuals. The overall prevalence rate of oral HPV infections was considerably higher in men having sex with men as compared to heterosexual men and women. CONCLUSION: The prevalence rates of oral HPV infection in European populations are comparable to the results of the studies conducted in the USA and Asia. However, the European studies did not focus on the risk factors for oral HPV infection in healthy populations. A statistically significant relationship between oral sex, smoking, and HPV infection as observed in extensive studies from the USA was confirmed by a single European study.

High level of Tregs is a positive prognostic marker in patients with HPV-positive oral and oropharyngeal squamous cell carcinomas.

BACKGROUND: Human papillomaviruses (HPVs) have been proved as one of the etiological factors of oropharyngeal squamous cell carcinoma (OPSCC). Patients with tumors of viral etiology have a lower recurrence rate and better prognosis. OPSCC is linked to an alteration in the immune system. Only a limited number of studies have correlated both the immunological parameters and HPV status with patient prognosis. The aim of this study was to determine whether HPV infection and the immunological status influence patient prognosis individually or in concurrence. MATERIAL AND METHODS: Sixty patients with oral and oropharyngeal carcinomas were enrolled. They were divided into HPV-positive and HPV-negative groups based on the expression of HPV 16 E6 mRNA. Basic lymphocyte subpopulations were determined in the peripheral blood by means of flow cytometry. RESULTS: Significantly better disease-specific survival (DSS) was observed in patients with HPV-positive tumors. Nodal status, tumor grade, recurrence, and CD8+/Tregs ratio were identified as factors influencing DSS. A higher level of Tregs and a lower ratio of CD8/Tregs influenced overall survival (OS) independently of HPV status and age. Patients with HPV-positive tumors and high levels of Tregs survived significantly better than patients from the other groups. CONCLUSION: Better survival is associated with HPV positivity and elevated Tregs levels. Our data suggest that HPV infection and Tregs do not influence patient prognosis in concurrence.

Epidermal growth factor receptor (EGFR) expression and mutations in the EGFR signaling pathway in correlation with anti-EGFR therapy in head and neck squamous cell carcinomas.

UNLABELLED: Epidermal growth factor receptor (EGFR) is an important therapeutic target and a poor prognosis factor in head and neck squamous cell carcinoma (HNSCC). The aim of the study was to analyze EGFR expression and KRAS and EGFR mutational status and to correlate it with treatment response to anti-EGFR therapy combined with radiotherapy in 29 patients with advanced head and neck squamous cell carcinomas (HNSCC).EGFR gene expression normalized to GAPDH and EGFR variant type III (EGFRvIII) was detected in tumor tissue using real time reverse transcription -PCR. The mutational status of the EGFR and KRAS genes was investigated by real time PCR with sequence specific primers.Gene expression median values were 3.1x10(8) GAPDH gene copies per µg of RNA, and 8x10(6) EGFR gene copies per µg of RNA. The median EGFR/GADPH ratio reached 0.14. Patients, who achieved complete response after Cetuximab combined with radiotherapy, had significantly higher expression of the EGFR gene in tumors than patients with partial remission or patient without treatment response. An EGFRvIII mutation was found in 20.7 % of patients and no association was found between this mutation and treatment response. 27 patients (93.1 %) had an EGFR gene wild type tumor, and deletion in exon 19 was found in two patients with a poor clinical outcome. Most of the patients (82.8%) had a KRAS wild type tumor; a p.Gly12Cys was found in three patients and a p.Gly12Val mutation in one. Presence of a p.Gly12Val mutation in the KRAS gene was associated with an absence of response to treatment. CONCLUSION: Our data suggest that KRAS mutation (p.Gly12Val) and somatic EGFR mutation located in exon 19 may contribute to the limited clinical response to therapy with cetuximab + radiotherapy. Higher EGFR gene expression serves as an independent indicator of good clinical response to EGFR-targeted therapy + radiotherapy.

Postoperative radiochemotherapy with weekly cisplatin in patients with head and neck cancer single-institution outcome analysis.

The objective of this study was to evaluate the feasibility, toxicity and efficacy of postoperative radiochemotherapy with weekly cisplatin in locoregionally advanced or high risk head and neck cancer in a single institutional setting. Patients with head and neck cancer of stage III/IV or patients with insufficient margins of resection were included in the study. Radiotherapy consisted of 70 Gy/ 7 weeks/ 35 fraction after R1/2 resection and 60-64 Gy/ 6-6,5 weeks/ 30-32 fraction after R0 resection, respectively. All patients received concurrent cisplatin 40 mg/m2 weekly. Between 7/2002 and 12/2008, 100 consecutive patients [WHO ≤ 2, male to female ratio 84/16, median age 54 years] were treated. Tumors of the oropharynx were the most frequent (49%) and stage IV was predominant (86%). 96% patients received the full radiation treatment as planned, median total tumor dose was 66 Gy. Omission of weekly cisplatin had been occurring frequently, the most frequent reason for its early cessation were hematological toxicities (34%). Grade 3/4 mucosal toxicity developed in 32%. No death was observed during the treatment. The late toxicities were acceptable, predominantly subcutaneous fibrosis and xerostomia in most of the cases. We recorded six cases of osteonecrosis. Two and half year overall survival, locoregional control, time to progression and disease free survival were 64%, 88%, 79% and 59%, respectively. Postoperative radiochemotherapy with weekly cisplatin is toxic, but tolerable and highly effective in terms of locoregional control and survival. Multivariete analysis revealed that the only prognostic factor for survival was primary surgery at the University centre.

HPV and other risk factors of oral cavity/oropharyngeal cancer in the Czech Republic.

OBJECTIVE: An association between high-risk human papillomavirus (HR HPV) infection and a risk of development of a subgroup of head and neck cancers has been proposed recently. The main risk factors of oral and oropharyngal cancer observed in our population are smoking and alcohol consumption. The incidence of oral/oropharyngeal tumours in the Czech Republic is relatively high and there are no data available about the prevalence of HPV DNA presence in these tumours. MATERIALS AND METHODS: Eighty patients with a primary oropharyngeal cancer were enrolled. The presence of HPV DNA has been evaluated by polymerase chain reaction in 68 cases from which the tumour tissue and demographical and clinical data were available. The typing of HPV was performed by nucleotide DNA sequencing. RESULTS: The HPV DNA was detected in 51.5% of samples tested. Among the HPV DNA positive tumours, 80% contained HPV16. In the analysed group there were 54 men and 14 women. The prevalence of HPV DNA was lower in oral (25%) than in oropharyngeal (57%) tumours, and higher in never smokers (100%) and never drinkers (68.8%). HPV DNA presence was not related to gender, age, number of lifetime sexual partners or practice of oral-genital sex, size of tumour or presence of regional metastases. CONCLUSIONS: The difference in the prevalence of HPV DNA positive tumours between cases of oral cavity and oropharyngeal carcinoma exposed and not exposed to tobacco or alcohol support the theory that HPV DNA positive tumours form an aetiologically distinct subgroup of head and neck tumours.

Subjective functional results 1 year after surgery and postoperative radiation for oropharyngeal carcinoma.

This study was conducted to find out what factors most influenced functional results and patient satisfaction at 1 year after treatment in a homogeneous group of patients who had undergone surgery and postoperative radiotherapy for the treatment of oropharyngeal carcinoma. Further aims were to find out the relation between the overall and specific disease-related results and to compare the two questionnaires used. The study group consisted of 102 patients, 23 women and 79 men, with an age range of 41-77 years (mean 45.7 years). Two questionnaires were used for evaluation. The University of Washington head and neck quality of life questionnaire (UW-QOL) includes information about nine disease-specific domains and three questions on general quality of life. The second questionnaire used was the performance status scale for head and neck cancer patients (PSS), containing information about three disease-specific domains. Functional results were influenced by the size of tumor and by the surgical method used. Results worsened with increasing T stage. The best results were found after pharyngotomy without mandibulotomy, worse results, following temporary mandibulotomy with osteosynthesis, and the poorest results were found in the group of patients who had undergone composite resection. Neither age and sex of the patients nor the course of healing influenced the functional results. All results were significantly correlated to one another. The general parameters were also closely related to specific domains. An important correlation was found between the parameters in the two questionnaires.

Prevalence of the sleep apnea syndrome in acromegaly population.

The prevalence of sleep apnea syndrome (SAS) in acromegaly is high. Consequences of SAS are serious and are associated with increased morbidity and mortality. The aim of this study was to assess the relative frequency and predictive factors for SAS in a group of patients with acromegaly (n=55). The presence of SAS was evaluated using the Polymesam device. Hormonal and clinical examination consisted of assessment of growth hormone, insulin-like growth factor I plasma levels, body mass index (BMI), neck circumference, age, sex, treatment modes of acromegaly and ear, nose and throat (ENT) examination. The relative frequency of SAS in our group of patients with acromegaly was 75%. Independent predictors of SAS were: increased activity of acromegaly, higher age and neck circumference. No association between SAS and BMI and ENT findings was observed. The role of gender was controversial.

Laryngeal papilloma--precancerous condition?

In a group of 179 patients treated for recurrent laryngeal papillomatosis 668 surgeries were performed in the years 1982-1995 in the Department of Otorhinolaryngology, Head and Neck Surgery in Prague. The group was divided into 77 patients with a juvenile form of papillomatosis and 102 patients with an adult form. The adult form was then divided into a multiple (65 patients) and solitary form (37 patients). Three patients with a juvenile form of papillomatosis were irradiated in advance. None of these patients developed a carcinoma. There were 3 cases (1.7%) of carcinoma in the whole group of patients with histologically verified papillomas during repeated previous surgeries. All 3 patients with malignancy had an adult form of papillomatosis, two with a multiple form and one with a solitary form. The intervals between the first treatment for papilloma and the diagnosis of carcinoma was 8, 3 and 2 years.The rates of malignant transformation of papillomas vary in the literature. We suppose, that because of the generally long interval between the diagnosis of papilloma and that of carcinoma, to make a final conclusion of a certain ratio is very difficult. We envisage that in our group of patients with papillomatosis new cases of carcinoma will occur in the future.

[The sleep apnea syndrome. Basic diagnostic and therapeutic possibilities]. / Syndrom spánkové apnoe. Základní diagnostické a terapeutické moznosti.

The sleep apnoea syndrome (SAS) involves impaired regular breathing during sleep. It causes poor quality sleep and thus subsequent somnolence in daytime, it leads to periodic oxygen desaturation and has serious cardiovascular consequences. The authors describe methods used for the diagnosis and quantification of the intensity of SAS which they used (all-night extended polysomnography, ambulatory equipment MESAM 4 and afternoon polysomnography) and they list also the main therapeutic procedures used in SAS.

[Complications of CO2 laser surgery in the head and neck]. / Komplikace CO2 laserové chirurgie v oblasti hlavy a krku.

The authors analyzed data in the literature on complications of laser surgery in otolaryngology. Subsequently they analyse and describe in detail the complications they observed and which they encountered after 611 laser operations. None of the described complications caused permanent damage of the patient or the attending staff. When the recommended safety provisions are respected, the authors consider laser surgery a safe surgical method.

[Inverted papillomas]. / Invertované papilomy.

Inverted papilloma is a relatively rare benign tumour of nasal mucosa and paranasal sinuses which approx. in 15% is connected with malignancy. The morphology, occurrence, etiology and biological behaviour of this tumour are dealt with. A group of 8 patients is presented. The significance of nasal polyps routine histologic investigation for early detection of these tumours is stressed. Various treatment possibilities are discussed and a therapeutic procedure based on radical surgery is suggested.

[Treatment of benign laryngeal diseases using a CO2 laser]. / Lécba benigních onemocnení hrtanu CO2 laserem.

CO2 laser surgery is becoming a part of larynx surgery. The authors inform about their experience in benign larynx tumours treatment. They present analysis of concrete therapeutic procedures in individual larynx affections. They conclude that laser surgery is an advantegous method for benign larynx tumours treatment.