Intratumor heterogeneity may contribute to the ambiguous clinical results on PD-L1 status as a predictor for immunotherapy response in patients with HNSCC. This decreases the utility of PD-L1 ...expression from single tumour biopsies as a predictive biomarker. In this prospective study, intratumor heterogeneity of PD-L1 expression in HNSCC was investigated with both Tumour Proportion Score (TPS) and Combined Positive Score (CPS). Thirty-three whole surgical specimens from 28 patients with HNSCC were included. PD-L1 expression in six random core biopsies from each surgical specimen was used to assess the concordance between multiple biopsies and the negative predictive value of a single negative core biopsy. With 1% cut off, 36% of the specimens were concordant with TPS and 52% with CPS. With a 50% cut-off value the concordance was 70% with TPS and 55% with CPS. Defining a tumour as positive if just a single-one of the biopsies was positive, the negative predictive value (NPV) of a single negative core biopsy was 38.9 and 0% (1% cut off), and 79.9% and 62.8% (50% cut off) for TPS and CPS, respectively. In conclusion, PD-L1 positivity varies markedly within the tumour, both with TPS and CPS, challenging the utility of this biomarker.
Significant variation in human papillomavirus (HPV) prevalence in oropharyngeal squamous cell carcinoma (OPSCC) across countries ranging from 11% in Brazil to 74% in New Zealand has been reported ...earlier. The aim of this study was to systematically review the most recently published studies on the occurrence of HPV in OPSCC globally. PubMed and Embase were systematically searched for articles assessing the occurrence of HPV+ OPSCC published between January 2016 and May 2021. Studies with a study period including 2015 and the following years were included. Both HPV DNA and/or p16 were accepted as indicators of HPV+ OPSCC. 31 studies were enrolled comprising 49,564 patients with OPSCC (range 12–42,024 patients per study) from 26 different countries covering all continents. The lowest occurrences of HPV+ OPSCC were observed in India (0%) and Spain (10%) and the highest occurrences were observed in Lebanon (85%) and Sweden (70%). We observed great variation in HPV prevalence in OPSCC worldwide varying from 0% to 85%. The highest occurrences of HPV+ OPSCC were found in general in Northern European countries, USA, Lebanon, China, and South Korea. We observed a trend of increase in HPV-positivity, indicating a mounting burden of HPV+ OPSCC.
Background
It has long been suggested that angiotensin‐converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (AT2s) have some degree of ‘cross‐reactivity' in causing angioedema. ...Therefore, caution has been advised when switching patients with ACEi‐related angioedema to an AT2.
Objectives
To clarify whether AT2s can be used safely in patients with a history of angioedema during ACEi treatment and to estimate the incidence rate of angioedema in patients subsequently treated with other antihypertensive drugs (beta‐adrenergic blockers, calcium channel blockers, thiazides and analogues) or no antihypertensives.
Methods
This is a nationwide retrospective registry‐based cohort study of the Danish population during the period 1994 to 2016, and it uses Danish health registries. Propensity score adjusted and conventional proportional hazards regression models have been employed.
Results
A total of 1 106 024 ACEi users were identified. In total, 5 507 (0.5%) of these patients had experienced angioedema during ACEi treatment and were included in the study. The highest risk of angioedema recurrence was associated with continued ACEi use at an adjusted hazard ratio of 1.45 (95% CI, 1.19 to 1.78). An inverse association was found between AT2s and angioedema (adjusted hazard ratio, 0.39; 95% CI, 0.30 to 0.51) compared with other antihypertensives (adjusted hazard ratios, 0.77 to 0.97).
Conclusions
Compared with other antihypertensive drugs, AT2s do not increase the incidence of angioedema in patients with previous ACEi‐related angioedema.
Click here to view the Editorial Comment by N. Javaud et al.
Background
The eighth international symposium for sentinel node biopsy (SNB) in head and neck cancer was held in 2018. This consensus conference aimed to deliver current multidisciplinary guidelines. ...This document focuses on the surgical aspects of SNB for oral cancer.
Method
Invited expert faculty selected topics requiring guidelines. Topics were reviewed and evidence evaluated where available. Data were presented at the consensus meeting, with live debate from panels comprising expert, nonexpert, and patient representatives followed by voting to assess the level of support for proposed recommendations. Evidence review, debate, and voting results were all considered in constructing these guidelines.
Results/Conclusion
A range of topics were considered, from patient selection to surgical technique and follow‐up schedule. Consensus was not achieved in all areas, highlighting potential issues that would benefit from prospective studies. Nevertheless these guidelines represent an up‐to‐date pragmatic recommendation based on current evidence and expert opinion.
role of human papillomavirus in head and neck cancer LAJER, CHRISTEL BRAEMER; BUCHWALD, CHRISTIAN VON
APMIS : acta pathologica, microbiologica et immunologica Scandinavica,
June/July 2010, Volume:
118, Issue:
6-7
Journal Article
Peer reviewed
Open access
Lajer CB, von Buchwald C. The role of human papillomavirus in head and neck cancer. APMIS 2010; 118: 510-519. Over the last 20 years, there has been increasing awareness of a subset of squamous cell ...carcinomas of the head and neck (HNSCC), i.e. HPV-positive HNSCC. These cancers seem to differ somewhat from HPV-negative HNSCC. Patients with HPV-positive HNSCC tend to be younger and have a lower intake of tobacco and alcohol. Distinct molecular profiles separate them from HPV-negative cancers and show similarities with HPV-positive cervical SCC. There is evidence that HPV-positive HNSCC is a sexually transmitted disease. Patients with HPV-positive HNSCC are often diagnosed at a late stage with large cystic lymph nodes in the neck. HPV-positive HNSCC show an affinity for the oropharynx, especially the tonsils and the base of the tongue, and tend to show low differentiation histopathologically. There is a better prognosis regardless of the treatment regimen for HPV-positive HNSCC compared with HPV-negative HNSCC, and this seems to be related to the immune system. Whether the new vaccines for HPV will protect not only against cervical cancer but also against HPV-positive HNSCC remains unknown.
In risk assessment of recurrence, papillary thyroid cancer (PTC) and follicular thyroid cancer (FTC) are often grouped together as differentiated thyroid cancer (DTC). However, while risk factors ...affecting recurrence of PTC are well established, risk factors for recurrence of FTC are not. This systematic review examines risk factors for recurrence of FTC and evaluates their significance.
A systematic search on PubMed and Embase was performed in September 2020, including studies evaluating risk factors for recurrence of FTC. A quality assessment of the enrolled studies was performed.
Nine studies (
= 1544 patients) from eight countries were included. The average recurrence rate was 13.6%, and distant metastasis (DM) constituted 64.8% of the recurrent cases. The risk factors examined were sex, age at diagnosis, primary tumor size, degree of invasiveness, focality, positive resection margin, lymph node (LN) metastasis, and DM at diagnosis. Risk factors correlated with recurrence of FTC were age older than 45 years, primary tumor size above 40 mm, widespread invasion, multifocality, positive resection margin, LN metastasis, and DM at diagnosis. Sex was not a statistically significant risk factor.
We identified seven risk factors associated with recurrence of FTC. Age and multifocality were found to be of greater impact regarding recurrence risk of FTC compared with PTC. Future research needs to address the impact of different risk factors for recurrence of FTC particularly including age, primary tumor size, angioinvasion, and mutational status.
Single‐cell RNA sequencing (scRNA‐seq) is a novel method enabling genetic characterization of tumor tissue at a single‐cell level. This study systematically reviewed the literature on studies using ...scRNA‐seq to characterize head and neck squamous cell carcinomas (HNSCCs). Seven studies were included, of which two studies performed scRNA‐seq on 20 patients in total, and five studies used scRNA‐seq data in a subsequent clinical study. The former mentioned two studies found intra‐tumoral genetic heterogeneity among malignant cells but genetic uniformity among non‐malignant cells. The five latter studies used scRNA‐seq data in various ways. Three studies identified biomarkers related to predicting whether a patient would benefit from immunotherapeutic treatment. One study characterized genes related to the perineural invasion. One study identified genes to be used in diagnostics. Further studies performing scRNA‐seq on HNSCC are required to continue the ongoing development and use of scRNA‐seq.
Distant progression (DP) in oropharyngeal squamous cell carcinoma (OPSCC) has significant impact on morbidity and mortality. This study systematically reviewed the literature on studies reporting ...location and timing of DP after human papillomavirus (HPV)+ or HPV− OPSCCs. PubMed, EMBASE, and the Cochrane Library were systematically searched for studies reporting DP in patients treated with curative intend for an OPSCC. Outcome was site of and time to DP stratified on HPV‐status. Seven studies (n = 1564; 77% HPV+) were included in which 313 patients (20%) developed a DP (70% HPV+). The most common site of DP was the lungs (n = 232) regardless of HPV‐status. Patients with HPV+ tumors were more prone to dissemination involving multiple sites (risk ratio = 16.49). There was no difference in time to DP when stratified on HPV‐status (P = .10). The pattern of but not time to DP was significantly different in patients with OPSCC when stratified on HPV‐status.
The aim was to determine the accuracy of anterior nasal swab in rapid antigen (Ag) tests in a low SARS‐CoV‐2 prevalence and massive screened community. Individuals, aged 18 years or older, who ...self‐booked an appointment for real‐time reverse transcriptase‐polymerase chain reaction (RT‐PCR) test in March 2021 at a public test center in Copenhagen, Denmark were included. An oropharyngeal swab was collected for RT‐PCR testing, followed by a swab from the anterior parts of the nose examined by Ag test (SD Biosensor). Accuracy of the Ag test was calculated with RT‐PCR as reference. We included 7074 paired conclusive tests (n = 3461, female: 50.7%). The median age was 48 years (IQR: 36–57 years). The prevalence was 0.9%, that is, 66 tests were positive on RT‐PCR. Thirty‐two had a paired positive Ag test. The sensitivity was 48.5% and the specificity was 100%. This study conducted in a low prevalence setting in a massive screening set‐up showed that the Ag test had a sensitivity of 48.5% and a specificity of 100%, that is, no false positive tests. The lower sensitivity is a challenge especially if Ag testing is not repeated frequently allowing this scalable test to be a robust supplement to RT‐PCR testing in an ambitious public SARS‐CoV‐2 screening.
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