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To compare the efficacy of different treatments for posterior semicircular canal benign paroxysmal positional vertigo (PC-BPPV) by using direct and indirect evidence from existing randomized data.Randomized case-control studies that compared the efficacy of various nonsurgical treatments in PC-BPPV patients at 1 week and 1 month of follow-up were comprehensively screened. Bayesian network meta-analysis was performed to evaluate direct and indirect treatment comparisons. We further conducted subgroup pairwise meta-analysis to explore the inconsistency between comparisons of the Epley versus a sham maneuver and the Epley versus the Semont maneuver.A total of 41 parallel, randomized controlled studies were included. The Epley with vestibular rehabilitation (EVR), Epley, Semont and Hybrid maneuvers were effective in eliminating nystagmus during a Dix-Hallpike test at 1 week of follow-up (odds ratios [ORs]: 11.41-23.8, 95% credible interval [CrI]: excluding null), among which EVR showed the best efficacy (the surface area under the cumulative ranking curves [SUCRA] = 77.5%). However, at 1 month of follow-up, only the Semont (rank first, SUCRA = 76.1%) and Epley maneuvers (rank second, SUCRA = 65.3%) were effective in eliminating nystagmus during a Dix-Hallpike test. In the pairwise subgroup meta-analysis, for patients younger than 55 years of age, the efficacy of the Epley maneuver was comparable to that of the Semont maneuver [rate ratio (RR): 0.99, 95% confidence interval (CI): 0.93-1.05]; for patients with a longer duration before treatment, the effect of the Epley maneuver was equivalent to that of a sham maneuver (RR: 1.07, 95% CI: 0.90-1.29).Among the 12 types of PC-BPPV treatments, the Epley, Semont, EVR, and Hybrid maneuvers were effective in eliminating nystagmus during a Dix-Hallpike test for PC-BPPV at 1 week of follow-up, whereas only the Epley and Semont maneuvers were effective at 1 month of follow-up. The duration before treatments and the age of patients might contribute to the efficacy of treatments.

The survival prognosis of human papillomavirus (HPV)-positive and HPV-negative head and neck squamous cell carcinoma (HNSCC) is largely different, and little is known about the anti-tumor mechanism of tumor-infiltrated exhausted CD8+ T cells (Tex) in HNSCC. We performed cell-level multi-omics sequencing on human HNSCC samples to decipher the multi-dimensional characteristics of Tex cells. A proliferative exhausted CD8+ T cell cluster (P-Tex) which was beneficial to survival outcomes of patients with HPV-positive HNSCC was identified. Interestingly, P-Tex cells expressed CDK4 genes as high as cancer cells, which could be simultaneously inhibited by CDK4 inhibitors and might be a potential reason for the ineffectiveness of CDK4 inhibitors in treating HPV-positive HNSCC. P-Tex cells could aggregate in the antigen-presenting cell niches and activate certain signaling pathways. Together, our findings suggest a promising role for P-Tex cells in the prognosis of patients with HPV-positive HNSCC by providing modest but persistent anti-tumor effects.

The survival prognosis of human papillomavirus (HPV)-positive and HPV-negative head and neck squamous cell carcinoma (HNSCC) is largely different, and little is known about the anti-tumor mechanism of tumor-infiltrated CD8+exhausted T cells (Tex) in HNSCC. We performed cell level multi-omics sequencing on human HNSCC samples to decipher the multi-dimensional characteristics of Tex cells. A proliferative exhausted CD8+T cell cluster (P-Tex) which was beneficial to survival outcomes of patients with HPV-positive HNSCC was identified. Interestingly, P-Tex cells expressed CDK4 genes as high as cancer cells, which could be simultaneously inhibited by CDK4 inhibitors and might be a potential reason for the ineffectiveness of CDK4 inhibitors in treating HPV-positive HNSCC. P-Tex cells could aggregate in the antigen presenting cell niches and activate certain signaling pathways. Together, our findings suggest a promising role for P-Tex cells in the prognosis of patients with HPV-positive HNSCC by providing modest but persistent anti-tumor effects.Graphic abstract