Search

The prognosis after primary (chemo-)radiotherapy for oropharyngeal squamous cell carcinoma (OPSCC) is affected by Human Papillomavirus (HPV) status, with a better prognosis in HPV-positive OPSCC. HPV-status is routinely assessed by p16 immunohistochemistry (IHC), but additional HPV DNA testing is debated. Also, there are numerous HPV genotypes, which prognostic role may need clarification. The purpose of this study was: (1) to test a custom-made targeted HPV next generation sequencing (NGS) panel in OPSCC, (2) to determine correlation with p16 IHC, and (3) to assess the impact of HPV DNA testing on outcome in the prospectively randomized clinical trial DAHANCA 19. We included 271 patients with OPSCC treated with primary (chemo-)radiotherapy in the DAHANCA 19 trial. Of these, 199 (73%) were p16-positive. HPV-status was determined by targeted HPV next generation sequencing (NGS), using a custom-made HPV genotyping panel. HPV was detected in 194 tumor samples. p16 IHC and NGS HPV status were concordant in 265 (98%) of 271 patients, whereas we did not detect HPV DNA in 5 p16-positive tumors. HPV16 accounted for 169 of 194 HPV-positive cases (87%). HPV genotypes 18, 31, 33, 35, and 59 were also detected. Loco-regional failure and overall survival were similar whether patients were separated by p16 IHC, or HPV DNA status (p < 0.0001 for all) and did not depend on HPV genotype (p = 0.9 and p = 0.7). In the present study, HPV DNA testing or typing in a Danish OPSCC cohort did not add additional information to p16 IHC, the most widely used and accepted prognostic indicator. [ABSTRACT FROM AUTHOR]

We compare outcomes in two large‐scale contemporaneously treated HPV‐positive (HPV+) oropharynx cancer (OPC) cohorts treated with definitive radiotherapy/chemoradiotherapy (RT/CRT). p16‐confirmed HPV+ OPC treated between 2007 and 2015 at PMH and DAHANCA were identified. Locoregional failure (LRF), distant metastasis (DM), and overall survival (OS) were compared. Multivariable analysis (MVA) calculated adjusted‐hazard‐ratio (aHR) with 95% confidence interval (95% CI), adjusting for cohort, age, gender, performance status, smoking pack‐years, T‐category and N‐category and chemotherapy. Compared to PMH (n = 701), DAHANCA (n = 1174) contained lower TNM‐8T‐categories (T1‐T2: 77% vs 56%), N‐categories (N0‐N1: 77% vs 67%) and stages (stage I: 63% vs 44% (all P <.001). PMH used standard‐fractionation CRT in 69% (481) while 31% (220) received hypofractionated or moderately accelerated RT‐alone. All DAHANCA patients were treated with moderately accelerated RT; 96% (1129) received nimorazole (NIM) and 73% (856) concurrent weekly cisplatin. DAHANCA had shorter overall‐treatment‐time (P <.001), lower gross tumor (66‐68 vs 70 Gy) and elective neck (50 vs 56 Gy) doses. Median follow‐up was 4.8 years. DAHANCA had higher 5‐year LRF (13% vs 7%, aHR = 0.47 [0.34‐0.67]), comparable DM (7% vs 12%, aHR = 1.32 [0.95‐1.82]), but better OS (85% vs 80%, aHR = 1.30 [1.01‐1.68]). CRT patients had a lower risk of LRF (aHR 0.56 [0.39‐0.82]), DM (aHR 0.70 [0.50‐1.00]) and death (aHR 0.39 [0.29‐0.52]) vs RT‐alone. We observed exemplary outcomes for two large‐scale trans‐Atlantic HPV+ OPC cohorts treated in a similar manner. Concurrent chemotherapy was a strong, independent prognostic factor for all endpoints. Our findings underscore the need for a very careful approach to de‐intensification of treatment for this disease. [ABSTRACT FROM AUTHOR]

A unique case of fetal goiter accompanied by bilateral ovarian cysts in a mother treated with methimazole for Graves'disease is reported. The abnormal findings were detected by ultrasound at 31 weeks of gestation. Umbilical fetal blood sampling revealed elevated serum TSH, normal concentrations of free T 4 , normal FSH and LH and high concentrations of E 2 . A series of weekly amniocenteses and intra-amniotic injections of levothyroxine was initiated, along with a reduction of the mother's methimazole dosage. The level of TSH in amniotic fluid was initially high, but was considerably reduced by each injection and followed by a gradual reduction of fetal goiter as well as the left ovarian cyst. The right cyst ruptured spontaneously. At 36 weeks + 4 days, the patient underwent elective caesarean section and gave birth to a female, weighing 2,880 g with 1- and 5-min Apgar scores of 10. The thyroid gland appeared normal in size, and cord blood TSH and free T 4 were both within normal limits. At ultrasound control 6 days later, the right ovarian cyst was not visible, while the left cyst was still present. Thus, our report supports previous findings that fetal goiter can be treated successfully with intra-amniotic injection of levothyroxine.More importantly, it shows that fetal hypothyroidism with elevated levels of TSH can be accompanied by ovarian cysts,suggesting interference between thyreotropic and gonadotropic hormones. [ABSTRACT FROM AUTHOR]

Objectives: To demonstrate the correlation between p16 overexpression and HPV in oropharyngeal carcinoma and to evaluate the prognostic impact of p16 status in a prospectively analyzed cohort of Danish oropharyngeal cancer patients. Materials and Methods: 32 tunsillar carcinomas were arranged in a Tissue Micro Array and evaluated by IHC for p16 overexpression. HPV-16 DNA detection was done by in situ hybridization. Between 1986 and 1999 The Danish Head and Neck Cancer group conducted the DAHANCA 5&7 randomized trials. In the present study 335 pre-treatment oropharyngeal tumour blocks from patients enrolled in these trials were evaluated by IHC for p16 status. Results: 20 of 32 (62.5%) tonsillar carcinomas were HPV-16 positive and 19 of these were p16 positive (sensitivity: 0.95). 12 turnouts were H PV-16 negative and 10 of these were p16 negative (specificity: 0.83). The two markers matched in 29 of 32 (90%) of the tumours. In total 135 of 335 (40%) oropharyngeal tumours were p16 positive. In univariate analysis, loco-regional turnout control was significantly improved for p16 positive tumours with 5-year actuarial values of 67% versus 36%, p < 0.0001. A similar beneficial outcome for p16 positive tumours was observed for cancer specific survival (69% versus 35%, p < 0.0001) and overall survival (54% versus 18%, p < 0.0001). In multivariate analysis p16 overexpression remained a very strong independent prognostic factor for loco-regional tumour control [OR: 0.35 (95% C.I. 0.24-0.51)], cancer specific death [OR: 0.28 (0.18-0.42)] and overall death [OR: 0.33 (0.24 0.46)] respectively. p16 was an even stronger prognostic factor related to these outcomes than T-stage and Nodal-status. Conclusions: p16 overexpression proved to be the strongest independent prognostic factor related to survival and loco-regional tumour control in our study and so we conclude that HPV infection is significantly correlated to improved prognosis and response to radiotherapy in oropharyngeal cancer patients. [ABSTRACT FROM AUTHOR]

Importance: The socioeconomic gap in survival after cancer is pronounced among patients with head and neck cancer. Understanding the mechanisms of this gap is crucial to target intervention strategies., Objective: To investigate socioeconomic differences in survival after oropharyngeal squamous cell carcinoma (OPSCC) according to human papillomavirus (HPV) status and the extent to which smoking, comorbidity, clinical stage, and treatment intent explain the survival gap., Design, Setting, and Participants: This nationwide, population-based cohort study was based on prospectively collected information on all patients with a diagnosis of OPSCC from the Danish Head and Neck Cancer Group database and administrative registries. The study included 4600 patients born in 1921 or later, aged 30 years or older, and residing in Denmark 1 year prior to OPSCC diagnosis. Patients with missing information (547 [12%]) were excluded. Patients were diagnosed between January 1, 2008, and December 31, 2019, and followed up until December 31, 2021. Data were analyzed from June 6 to October 4, 2022., Exposure: Socioeconomic position (educational level, disposable income, or cohabiting status)., Main Outcomes and Measures: Socioeconomic differences in 5-year overall survival were estimated in Cox proportional hazards regression models by HPV status. The indirect effect and proportion mediated by smoking, comorbidity, clinical stage, and treatment intent were estimated based on a counterfactual approach., Results: The analyzed cohort comprised 4053 patients (1045 women [26%] and 3008 men [74%]). The median age was 61 years (IQR, 55-68 years), and 2563 patients (63%) had HPV-positive OPSCC while 1490 patients (37%) had HPV-negative OPSCC. The 5-year standardized overall survival was 10% to 15% lower among patients with a lower educational level, with low disposable income, or who were living alone (patients with HPV-positive OPSCC, 68%-71%; patients with HPV-negative OPSCC, 31%-34%) than patients with a higher educational level, high disposable income, or a cohabiting partner (patients with HPV-positive OPSCC, 81%-86%; patients with HPV-negative OPSCC, 43%-46%). Among patients with HPV-positive OPSCC, a considerable part of this survival gap was estimated to be associated with differences in smoking (27%-48%), comorbidity (10%-19%), clinical stage (8%-19%), and treatment intent (16%-28%). Among those with HPV-negative OPSCC, comorbidity (12%-22%) and treatment intent (16%-42%) were the primary potential mediators., Conclusions and Relevance: This cohort study suggests that, regardless of HPV status, patients with low socioeconomic position had 10% to 15% lower 5-year overall survival than patients with high socioeconomic position. A substantial part of this survival gap was associated with differences in smoking, comorbidity, clinical stage, or treatment intent at diagnosis.

We describe the case of a woman, aged 41 years, who received a combination chemotherapy including vincristine, doxorubicine, ifosfamide and etoposide due to Ewings sarcoma. She was treated prophylactic with fluconazole to prevent oral candidosis. Unexpectedly, she developed severe neurotoxic side effects. Treatment with multiple substrates of cytochrome P450 3A4 combined with inhibition of the enzyme by fluconazole impairs metabolism and thereby increase plasma concentrations of vincristine, which is considered to be the main reason for the neurotoxic side effects.