Public awareness of the association between human papillomavirus and oropharyngeal cancer.

BACKGROUND: Early diagnosis of human papillomavirus (HPV) associated oropharyngeal cancer (OPC) is associated with improved survival. To achieve early diagnosis, it might be beneficial to increase awareness of the link between HPV and OPC. This increase of awareness could also be an important way to increase vaccination rates. The aim of our study was to explore the current public knowledge in the Netherlands regarding the association of HPV with OPC. METHODS: An online cross-sectional survey was used and sent by the company Flycatcher Internet Research to 1539 of their panel members. Data were analyzed statistically by gender, age, educational level and the participants' use of alcohol and tobacco. RESULTS: The response rate was 68% (1044 participants). Our data revealed that 30.6% of the participants had heard of HPV. There was a knowledge gap regarding HPV in males (P < 0.001), people older than 65 years (P < 0.001), people with low education level (P < 0.001) and current smokers (P < 0.001). Of the respondents who had heard of HPV, only 29.2% knew of the association between HPV and OPC. We also found that only 49.7% of the population knew of the existence of an HPV vaccine. CONCLUSIONS: The results of this survey indicate that the public awareness of HPV and the association of HPV with OPC is lacking. Interventions to increase awareness of HPV and its association with non-cervical cancer should be considered. This might help to increase the HPV vaccine uptake both for girls and boys and earlier diagnosis of this disease leading to improved survival.

Upregulation of AKR1C1 and AKR1C3 expression in OPSCC with integrated HPV16 and HPV-negative tumors is an indicator of poor prognosis.

Different studies have shown that HPV16-positive OPSCC can be subdivided based on integration status (integrated, episomal and mixed forms). Because we showed that integration neither affects the levels of viral genes, nor those of virally disrupted human genes, a genome-wide screen was performed to identify human genes which expression is influenced by viral integration and have clinical relevance. Thirty-three fresh-frozen HPV-16 positive OPSCC samples with known integration status were analyzed by mRNA expression profiling. Among the genes of interest, Aldo-keto-reductases 1C1 and 1C3 (AKR1C1, AKR1C3) were upregulated in tumors with viral integration. Additionally, 141 OPSCC, including 48 HPV-positive cases, were used to validate protein expression by immunohistochemistry. Results were correlated with clinical and histopathological data. Non-hierarchical clustering resulted in two main groups differing in mRNA expression patterns, which interestingly corresponded with viral integration status. In OPSCC with integrated viral DNA, often metabolic pathways were deregulated with frequent upregulation of AKR1C1 and AKR1C3 transcripts. Survival analysis of 141 additionally immunostained OPSCC showed unfavorable survival rates for tumors with upregulation of AKR1C1 or AKR1C3 (both p <0.0001), both in HPV-positive (p ≤0.001) and -negative (p ≤0.017) tumors. OPSCC with integrated HPV16 show upregulation of AKR1C1 and AKR1C3 expression, which strongly correlates with poor survival rates. Also in HPV-negative tumors, upregulation of these proteins correlates with unfavorable outcome. Deregulated AKR1C expression has also been observed in other tumors, making these genes promising candidates to indicate prognosis. In addition, the availability of inhibitors of these gene products may be utilized for drug treatment.

Awareness of HPV-associated oropharyngeal cancers among GPs in The Netherlands: a cross-sectional study.

BACKGROUND: The incidence of human papillomavirus (HPV)-associated oropharyngeal cancer (OPC) is increasing in high income countries. HPV-associated OPC generally presents as an invasive disease, often with lymph node involvement, in relatively young patients with minimal or no history of smoking and alcohol consumption. Knowledge on HPV-associated OPC among primary care professionals is essential for disease recognition and early start of treatment. AIM: To examine the knowledge on HPV-associated OPC among GPs in the Netherlands. DESIGN & SETTING: A cross-sectional postal survey among GPs in the Netherlands. METHOD: A 12-item questionnaire was sent to 900 randomly selected general practices. Outcome measures included awareness of the link between HPV and OPC, epidemiological trends, and patient characteristics. Data were statistically analysed for sex, years after graduation, and self-rated knowledge of OPC. RESULTS: A total of 207 GPs participated in this study. Seventy-two per cent recognised HPV as a risk factor for OPC and 76.3% were aware of the increasing incidence rate of HPV-associated OPC. In contrast, 35.7% of participants knew that patients with HPV-associated OPC are more often male, and just over half (53.6%) of the participants were aware of the younger age of these patients. CONCLUSION: More than one-quarter of GPs in the Netherlands are unaware of HPV as a causative factor for OPC. Furthermore, there is a gap in knowledge on characteristics of patients with HPV-associated OPC . Further training on these topics could improve disease recognition and, ultimately, patient survival.

EAT-10 Scores and Fiberoptic Endoscopic Evaluation of Swallowing in Head and Neck Cancer Patients.

OBJECTIVE: The purpose of this study was to determine the relationship between patient-reported symptoms of oropharyngeal dysphagia (OD) using the Eating Assessment Tool (EAT)-10 and the swallowing function using a standardized fiberoptic endoscopic evaluation of swallowing (FEES) protocol in head and neck cancer (HNC) patients with confirmed OD. METHODS: Fifty-seven dysphagic HNC patients completed the EAT-10 and a FEES. Two blinded clinicians scored the randomized FEES examinations. Exclusion criteria consisted of presenting with a concurrent neurological disease, scoring below 23 on a Mini-Mental State Examination, being older than 85 years, having undergone a total laryngectomy, and being illiterate or blind. Descriptive statistics, linear regression, sensitivity, specificity, and predictive values were calculated. RESULTS: The majority of the dysphagic patients (N = 38; 66.7%) aspirated after swallowing thin liquid consistency. A large number of patients showed postswallow pharyngeal residue while swallowing thick liquid consistency. More specifically, 42 (73.0%) patients presented postswallow vallecular residue, and 39 (67.9%) patients presented postswallow pyriform sinus residue. All dysphagic patients had an EAT-10 score ≥ 3. Linear regression analyses showed significant differences in mean EAT-10 scores between the dichotomized categories (abnormal vs. normal) of postswallow vallecular (P = .037) and pyriform sinus residue (P = .013). No statistically significant difference in mean EAT-10 scores between the dichotomized categories of penetration or aspiration was found (P = .966). CONCLUSION: The EAT-10 questionnaire seems to have an indicative value for the presence of postswallow pharyngeal residue in dysphagic HNC patients, and a value of 19 points turned out to be useful as a cutoff point for the presence of pharyngeal residue in this study population. LEVEL OF EVIDENCE: 2B.

The Antiviral Agent Cidofovir Induces DNA Damage and Mitotic Catastrophe in HPV-Positive and -Negative Head and Neck Squamous Cell Carcinomas In Vitro.

Cidofovir (CDV) is an antiviral agent with antiproliferative properties. The aim of our study was to investigate the efficacy of CDV in HPV-positive and -negative head and neck squamous cell carcinoma (HNSCC) cell lines and whether it is caused by a difference in response to DNA damage. Upon CDV treatment of HNSCC and normal oral keratinocyte cell lines, we carried out MTT analysis (cell viability), flow cytometry (cell cycle analysis), (immuno) fluorescence and western blotting (DNA double strand breaks, DNA damage response, apoptosis and mitotic catastrophe). The growth of the cell lines was inhibited by CDV treatment and resulted in γ-H2AX accumulation and upregulation of DNA repair proteins. CDV did not activate apoptosis but induced S- and G2/M phase arrest. Phospho-Aurora Kinase immunostaining showed a decrease in the amount of mitoses but an increase in aberrant mitoses suggesting mitotic catastrophe. In conclusion, CDV inhibits cell growth in HPV-positive and -negative HNSCC cell lines and was more profound in the HPV-positive cell lines. CDV treated cells show accumulation of DNA DSBs and DNA damage response activation, but apoptosis does not seem to occur. Rather our data indicate the occurrence of mitotic catastrophe.

Relationship between swallow-specific quality of life and fiber-optic endoscopic evaluation of swallowing findings in patients with head and neck cancer.

BACKGROUND: The purpose of this study was to determine the relationship between swallow-specific quality of life (QOL) using the MD Anderson Dysphagia Inventory (MDADI) and the swallowing function using a standardized fiber-optic endoscopic evaluation of swallowing (FEES) protocol in patients with dysphagia with head and neck cancer. METHODS: Sixty-three patients with dysphagia and head and neck cancer were enrolled in the study. Patients completed the MDADI questionnaire and underwent a standardized FEES examination. Ordinal FEES variables were measured. Descriptive statistics and 1-way analysis of variance tests were carried out. RESULTS: For all FEES variables, the observer agreement level was sufficient (kappa ≥0.7).These preliminary results show statistically significant mean differences of MDADI subscales between the ordinal scale levels for several FEES variables. CONCLUSION: The MDADI questionnaire can be used to assess the impact of dysphagia on the patients' health-related QOL. Despite clear trends, it remains unclear if the MDADI questionnaire can be used as an indicator for the severity of oropharyngeal dysphagia. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1848-E1856, 2016.

Lexical frequency and voice assimilation.

Acoustic duration and degree of vowel reduction are known to correlate with a word's frequency of occurrence. The present study broadens the research on the role of frequency in speech production to voice assimilation. The test case was regressive voice assimilation in Dutch. Clusters from a corpus of read speech were more often perceived as unassimilated in lower-frequency words and as either completely voiced (regressive assimilation) or, unexpectedly, as completely voiceless (progressive assimilation) in higher-frequency words. Frequency did not predict the voice classifications over and above important acoustic cues to voicing, suggesting that the frequency effects on the classifications were carried exclusively by the acoustic signal. The duration of the cluster and the period of glottal vibration during the cluster decreased while the duration of the release noises increased with frequency. This indicates that speakers reduce articulatory effort for higher-frequency words, with some acoustic cues signaling more voicing and others less voicing. A higher frequency leads not only to acoustic reduction but also to more assimilation.