Double positivity for HPV DNA/p16 in tonsillar and base of tongue cancer improves prognostication: Insights from a large population-based study.

The aim was to explore the overall survival (OS) for palatine tonsillar squamous cell carcinoma (TSCC), subdivided, according to certainty of tonsillar tumour origin, into specified tonsillar squamous cell carcinomas (STSCCs) and nonspecified tonsillar squamous cell carcinomas (NSTSCCs), and base of tongue squamous cell carcinoma (BSCC) when stratifying for HPV DNA status, p16 expression and combined HPV/p16 status. We included all patients (n = 797) diagnosed with TSCCs and BSCCs in Eastern Denmark as registered in the Danish Head and Neck Cancer Group (DAHANCA) database and the Danish Pathology Databank, 2000-2010. Patients were treated according to national guidelines (radiotherapy +/- concomitant cisplatin). All specimens were analysed using HPV DNA PCR and p16 immunohistochemistry. Clinical information was retrieved from the DAHANCA database and the Danish National Patient Registry. Information on vital status was obtained from the Danish Civil Registration System. We observed improved OS for HPV+/p16+ BSCCs compared to HPV-/p16- (hazard ratio for death [HR], 0.15; 95% CI, 0.09-0.24). Among STSCCs, HPV+/p16+ showed the lowest HR (0.19, 95% CI, 0.13-0.29); whereas, HPV-/p16+ showed an intermediate HR (0.39; 95% CI, 0.22-0.70). For NSTSCCs, HPV+/p16+ and HPV-/p16+ showed similar OS (HRs, 0.39; 95% CI, 0.26-0.59; and 0.48; 95% CI, 0.24-0.95, respectively). Combined HPV+/p16+ was a significantly better prognostic marker in BSCCs and STSCCs than HPV DNA and p16, alone (all p-values < 0.05). Whereas, combined testing in NSTSCC was not better than p16 (p = 0.53), alone. In conclusion, double positivity for HPV/p16 in conjunction with the certainty of tumour site improved prognosis.

A high and increasing HPV prevalence in tonsillar cancers in Eastern Denmark, 2000-2010: the largest registry-based study to date.

The aim was to explore whether the incidence of tonsillar squamous cell carcinomas (TSCCs) increased in Eastern Denmark, 2000-2010, and whether human papillomavirus (HPV) could explain the increase, and to assess the association of HPV prevalence with gender, age, and origin (i.e., the certainty of tonsillar tumor origin). We applied HPV DNA PCR and p16 immunohistochemistry to all TSCCs registered in the Danish Head and Neck Cancer Group (DAHANCA) and in the Danish Pathology Data Bank (n = 632). Pathologists reviewed and subdivided the tumors into two groups: specified and nonspecified TSCCs. Approximately 10% of HPV-positive tumors was genotyped by amplicon next-generation sequencing. The overall crude incidence of TSCCs increased significantly (2.7% per year) and was explained by an increasing incidence of HPV-positive TSCCs (4.9% per year). The overall HPV prevalence was 58%, with HPV16 being the predominant HPV type. In multivariate analysis, the HPV prevalence was associated with age (<55 vs. >60 years) (OR, 1.72; 95% CI 1.13-2.63) and origin (nonspecified vs. specified TSCCs) (OR, 0.15; 95% CI 0.11-0.22). The association of HPV prevalence with origin increased over time in specified TSCCs (OR per year, 1.10; 95% CI 1.01-1.19), whereas no change over time was observed among nonspecified TSCCs (OR per year, 0.99; 95% CI 0.90-1.08). In conclusion, the observed increase in the number of HPV-positive TSCCs can explain the increasing number of TSCCs in Eastern Denmark, 2000-2010. HPV prevalence was associated with younger age (<55 years) and a high certainty of tonsillar tumor origin.

Three fatal cases of PMA and PMMA poisoning in Denmark.

Paramethoxyamphetamine (PMA) and paramethoxymetamphetamine (PMMA) are methoxylated phenylethylamine derivatives with effects similar to methylenedioxymetamphetamine (MDMA) and sold as such. However, PMA and PMMA are more potent than MDMA, but have a slower onset of action, which encourages users to take more. Three fatal cases involving PMA and PMMA in Denmark in year 2000 are investigated including history, pathological, and toxicological findings. The methods used for extraction, identification, and quantitation of PMA and PMMA are described. In two of the cases, lethal postmortem blood concentrations of PMA and PMMA were determined at 3.4 and 3.3 mg/kg (case 1) and 0.78 and 0.68 mg/kg (case 3), respectively. In addition, other drugs such as MDMA, tetrahydrocannabinol, cocaine, and alcohol were involved in these cases. In the third case, death occurred four days after the ingestion of tablets containing PMA and PMMA, and therefore only low postmortem concentrations of PMA and amphetamine were detected. However, in a serum sample taken at admission to the hospital, PMA and PMMA were found, but not quantitated. It is believed that the cause of death in case 2, multiple-organ failure, was caused by overdoses of PMA and PMMA.