Sex-specific aspects in patients with oropharyngeal squamous cell carcinoma: a bicentric cohort study.

BACKGROUND: Oropharyngeal squamous cell carcinoma (OPSCC) is the only subgroup of head neck cancer that presents with an increased incidence. Gender-specific studies in other cancer entities have revealed differences in treatment response and prognosis. However, only limited data in OPSCC according to gender and human papillomavirus (HPV) status exist. Therefore, we aimed to investigate sex-specific differences in OPSCC and how these may be distributed in relation to HPV and other risk factors. METHODS: This retrospective, bicentric study included 1629 patients with OPSCC diagnosed between 1992 and 2020. We formed subgroups based on TNM status, American Joint Cancer Committee 8th edition (AJCC8), HPV status, treatment modality (surgery (± radio(chemo)therapy (RCT) vs. definitive RCT) and patient-related risk factors and investigated gender differences and their impact on patients survival via descriptive-,uni- and multivariate analysis. RESULTS: With the exception of alcohol abuse, no significant differences were found in risk factors between men and women. Females presented with better OS than males in the subgroup T1-2, N + , independent of risk factors (p = 0.008). Males demonstrated significant stratification through all AJCC8 stages (all p < 0.050). In contrast, women were lacking significance between stage II and III (p = 0.992). With regard to therapy (surgery (± R(C)T) - vs. definitive RCT) women treated with surgery had better OS than men in the whole cohort (p = 0.008). Similar results were detected in the HPV-negative OPSCC sub-cohort (p = 0.042) and in high-risk groups (AJCC8 stage III and IV with M0, p = 0.003). CONCLUSION: Sex-specific differences in OPSCC represent a health disparity, particularly according to staging and treatment, which need to be addressed in future studies.

Herbarium records indicate variation in bloom-time sensitivity to temperature across a geographically diverse region.

Anthropogenic warming's effects on phenology across environmental and temporal gradients are well recognized. Long-term phenological monitoring data are often limited in duration and geographic scope, but recent efforts to digitize herbaria collections make it possible to reliably reconstruct historic flowering phenology across broad geographic scales and multiple species, lending to an increased understanding of community response to climate change. In this study, we examined collection dates (1901 to 2015) of 8540 flowering specimens from 39 native species in the Pacific Northwest (PNW) region of North America. We hypothesized that flowering phenology would be sensitive to temperature but that sensitivity would vary depending on blooming season and geographic range position. As expected, we found that early-season bloomers are more sensitive to temperature than later-season bloomers. Sensitivity to temperature was significantly greater at low elevations and in the maritime (western) portion of the PNW than at higher elevations and in the eastern interior, respectively. The elevational and longitudinal effects on flowering sensitivity reflect spring "arriving" earlier at low elevations and in the maritime portion of the PNW. These results demonstrate that phenological responses to warming vary substantially across climatically diverse regions, warranting careful and nuanced consideration of climate warming's effects on plant phenology.

Fire sparks upslope range shifts of North Cascades plant species.

As ongoing climate change drives suitable habitats to higher elevations, species ranges are predicted to follow. However, observed range shifts have been surprisingly variable, with most species differing in rates of upward shift and others failing to shift at all. Disturbances such as fires could play an important role in accelerating range shifts by facilitating recruitment in newly suitable habitats (leading edges) and removing adults from areas no longer suited for regeneration (trailing edges). To date, empirical evidence that fires interact with climate change to mediate elevational range shifts is scarce. Resurveying historical plots in areas that experienced climate change and fire disturbance between surveys provides an exciting opportunity to fill this gap. To investigate whether species have tended to shift upslope and if shifts depend on fires, we resurveyed historical vegetation plots in North Cascades National Park, Washington, USA, an area that has experienced warming, drying, and multiple fires since the original surveys in 1983. We quantified range shifts by synthesizing across two lines of evidence: (1) displacement at range edges and the median elevation of species occurrences, and (2) support for the inclusion of interactions among time, fire and elevation in models of species presence with elevation. Among species that experienced fire since the original survey, a plurality expanded into new habitats at their upper edge. In contrast, a plurality of species not experiencing fire showed no evidence of shifts, with the remainder exhibiting responses that were variable in magnitude and direction. Our results suggest that fires can facilitate recruitment at leading edges, while species in areas free of disturbance are more likely to experience stasis.

Predicting HPV association using deep learning and regular H&E stains allows granular stratification of oropharyngeal cancer patients.

Human Papilloma Virus (HPV)-associated oropharyngeal squamous cell cancer (OPSCC) represents an OPSCC subgroup with an overall good prognosis with a rising incidence in Western countries. Multiple lines of evidence suggest that HPV-associated tumors are not a homogeneous tumor entity, underlining the need for accurate prognostic biomarkers. In this retrospective, multi-institutional study involving 906 patients from four centers and one database, we developed a deep learning algorithm (OPSCCnet), to analyze standard H&E stains for the calculation of a patient-level score associated with prognosis, comparing it to combined HPV-DNA and p16-status. When comparing OPSCCnet to HPV-status, the algorithm showed a good overall performance with a mean area under the receiver operator curve (AUROC) = 0.83 (95% CI = 0.77-0.9) for the test cohort (n = 639), which could be increased to AUROC = 0.88 by filtering cases using a fixed threshold on the variance of the probability of the HPV-positive class - a potential surrogate marker of HPV-heterogeneity. OPSCCnet could be used as a screening tool, outperforming gold standard HPV testing (OPSCCnet: five-year survival rate: 96% [95% CI = 90-100%]; HPV testing: five-year survival rate: 80% [95% CI = 71-90%]). This could be confirmed using a multivariate analysis of a three-tier threshold (OPSCCnet: high HR = 0.15 [95% CI = 0.05-0.44], intermediate HR = 0.58 [95% CI = 0.34-0.98] p = 0.043, Cox proportional hazards model, n = 211; HPV testing: HR = 0.29 [95% CI = 0.15-0.54] p < 0.001, Cox proportional hazards model, n = 211). Collectively, our findings indicate that by analyzing standard gigapixel hematoxylin and eosin (H&E) histological whole-slide images, OPSCCnet demonstrated superior performance over p16/HPV-DNA testing in various clinical scenarios, particularly in accurately stratifying these patients.

Experimental warming differentially affects vegetative and reproductive phenology of tundra plants.

Rapid climate warming is altering Arctic and alpine tundra ecosystem structure and function, including shifts in plant phenology. While the advancement of green up and flowering are well-documented, it remains unclear whether all phenophases, particularly those later in the season, will shift in unison or respond divergently to warming. Here, we present the largest synthesis to our knowledge of experimental warming effects on tundra plant phenology from the International Tundra Experiment. We examine the effect of warming on a suite of season-wide plant phenophases. Results challenge the expectation that all phenophases will advance in unison to warming. Instead, we find that experimental warming caused: (1) larger phenological shifts in reproductive versus vegetative phenophases and (2) advanced reproductive phenophases and green up but delayed leaf senescence which translated to a lengthening of the growing season by approximately 3%. Patterns were consistent across sites, plant species and over time. The advancement of reproductive seasons and lengthening of growing seasons may have significant consequences for trophic interactions and ecosystem function across the tundra.

Author Correction: Warming shortens flowering seasons of tundra plant communities.

In the version of this Article originally published, the following sentence was missing from the Acknowledgements: "This work was supported by the Norwegian Research Council SnoEco project, grant number 230970". This text has now been added.

Warming shortens flowering seasons of tundra plant communities.

Advancing phenology is one of the most visible effects of climate change on plant communities, and has been especially pronounced in temperature-limited tundra ecosystems. However, phenological responses have been shown to differ greatly between species, with some species shifting phenology more than others. We analysed a database of 42,689 tundra plant phenological observations to show that warmer temperatures are leading to a contraction of community-level flowering seasons in tundra ecosystems due to a greater advancement in the flowering times of late-flowering species than early-flowering species. Shorter flowering seasons with a changing climate have the potential to alter trophic interactions in tundra ecosystems. Interestingly, these findings differ from those of warmer ecosystems, where early-flowering species have been found to be more sensitive to temperature change, suggesting that community-level phenological responses to warming can vary greatly between biomes.

A novel treatment approach prolonging survival in an uncommon metastatic primary bladder adenocarcinoma.

Primary bladder adenocarcinoma (PBA) is an epithelial malignancy with pure glandular differentiation, without evidence of typical urothelial (transitional cell) carcinoma. PBA is rare, accounting for 0.5%-2% of all malignant bladder neoplasms, and it is seen more frequently in men than in women and is commonly diagnosed in the sixth decade of life.¹â»³ Clinical presentation includes hematuria and symptoms of bladder irritation.² PBA is common in schistosomiasis-endemic regions and among patients with congenital bladder exstrophy (ectopia vesicae); it mostly arises in the trigone and posterior bladder wall.4 In contrast, urachal adenocarcinomas arise within urachal remnants (residual tissues from the embryonic allantoic stalk connecting the umbilicus and bladder), close to the dome and anterior wall of the bladder. Morphologically, PBA is classifed into enteric and nonenteric types, which includes mucinous, signetring cell variant, clear-cell type, hepatoid, and mixed forms.² Currently, there is no standard of care in the management of PBA. We present the case of a patient with metastatic PBA with intestinal differentiation and wild-type KRAS, who was treated with colorectal cancer regimens.

A Range-Expanding Shrub Species Alters Plant Phenological Response to Experimental Warming.

Shifts in plant species phenology (the timing of life-history events such as flowering) have been observed worldwide in concert with rising global temperatures. While most species display earlier phenology with warming, there is large variation among, and even within, species in phenological sensitivity to rising temperatures. Other indirect effects of climate change, such as shifting species composition and altered species interactions, may also be contributing to shifting plant phenology. Here, we describe how experimental warming and the presence of a range-expanding species, sagebrush (Artemisia rothrockii), interact to influence the flowering phenology (day of first and peak flowering) and production (number of flowers) of an alpine cushion plant, Trifolium andersonii, in California's White Mountains. Both first flowering and peak flowering were strongly accelerated by warming, but not when sagebrush was present. Warming significantly increased flower production of T. andersonii, but less so in the presence of sagebrush. A shading treatment delayed phenology and lowered flower production, suggesting that shading may be the mechanism by which sagebrush presence delayed flowering of the understory species. This study demonstrates that species interactions can modify phenological responses to climate change, and suggests that indirect effects of rising temperatures arising from shifting species ranges and altered species interactions may even exceed the direct effects of rising temperatures on phenology.