Cancer journal最新文献

Human papillomavirus is associated with the development of malignancies in the head and neck region, particularly oropharyngeal carcinoma. In recent years, there has been a significant increase in these virally mediated cancers, largely due to HPV strains 16 and 18. Existing literature supports a reduction in oral HPV infection following vaccination, and the FDA recently expanded the indication for the nonvalent Gardasil vaccine for use in HPV-related head and neck cancers in both men and women. The objectives of this paper are to review the evidence supporting the use of HPV vaccination in head and neck cancer, introduce HPV vaccinations currently being investigated in clinical trials, and assess barriers to production and widespread use of these vaccinations.

Traditional surgical approaches to all oropharyngeal cancer included open surgery via mandibulotomy or mandibular swing procedures-extensive surgery that often led to tracheostomy, gastrostomy tube dependence, and prolonged hospital stay. As HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) began to increase in prevalence, it became clear that this new disease entity was associated with improved survival. There was therefore a strong desire from surgeons and oncologists to reduce the morbidity associated with its management. The paradigm shift to transoral robotic surgery and transoral laser microsurgery for selected patients with HPV oropharynx cancer has allowed for avoidance of tracheostomy, mandibulotomy, and feeding tube while preserving speech and swallow function. Current research focuses on de-escalating adjuvant treatment in appropriate cases to reduce morbidity without impacting oncologic outcome.

Standard of care for locoregionally advanced HPV-positive OPSCC is definitive chemoradiation with doses up to 70 Gy and concurrent cisplatin. Radiation techniques have evolved considerably from 3D conformal radiotherapy (3D CRT) to the now widely used intensity-modulated radiotherapy (IMRT) and volumetric modulated arc radiotherapy (VMAT). Many centers are also incorporating stereotactic body radiation therapy (SBRT) and proton therapy to deliver even more conformal treatments that can minimize dose to normal organs at risk, thereby improving the therapeutic ratio. We review here the advancements and current landscape of radiation therapy for HPV+ OPSCC.

HPV+ oropharyngeal cancer represents a unique disease entity in the realm of head and neck cancer with distinct incidence and prevalence, pathogenesis, and treatment outcome. Management of this disease needs to be personalized in consideration of a combination of factors of both patient and disease characteristics. Overall outcomes in this patient population are excellent. Therefore, late side effects of treatment are gaining increasing importance and attention. Here we present a brief overview of personalized approaches for this patient population, illustrated by a discussion of several cases.

This review highlights recent advances in systemic and immunotherapy for patients with HPV-mediated oropharynx cancer. Over the last 20 years, therapies have evolved from cytotoxic agents alone to those that target mechanisms of treatment resistance and/or activate the immune system. This article discusses therapies used in definitive and/or recurrence/metastatic treatment. For each setting, current standards of care and areas of active clinical investigation are discussed.

Human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) presents a favorable prognosis compared with its HPV-negative counterpart, prompting interest in treatment de-escalation to reduce toxicity. However, attempts using risk factors, stage, and HPV status alone have not proven sufficient. Circulating tumor DNA (ctDNA) has emerged as a promising biomarker to personalize treatment by detecting tumor burden, monitoring minimal residual disease (MRD), and guiding response-adaptive therapy. This review evaluates the role of ctDNA across the clinical course-from diagnosis to mid-treatment monitoring to post-treatment surveillance. It highlights ctDNA's potential to enhance diagnostic accuracy, guide treatment deintensification, and detect recurrence through a summary of recent and ongoing clinical trials. However, limitations in assay sensitivity and the need for prospective validation restrict its current clinical utility. Ongoing clinical trials will be pivotal in determining whether ctDNA can reliably support personalized de-escalation strategies in HPV+ OPSCC.

mRNA vaccines consist of antigen-encoding mRNA, which produces the antigenic protein upon translation. Coupling antigen production with innate immune activation can generate a potent, antigen-specific T-cell response. Clinical reports have demonstrated the ability of mRNA vaccines to elicit an anticancer immune response against various tumor types. Here, we discuss strategies to enhance the potency of mRNA vaccines. We provide an overview of existing knowledge regarding the activation and trafficking mechanisms of mRNA vaccines and share optimization strategies to boost mRNA-mediated antigen production. In addition, we address methods to target mRNA vaccines to dendritic cells and lymph nodes, key initiators of the immune response. Finally, we review strategies for enhancing immune activation using adjuvants compatible with mRNA vaccines. mRNA vaccines offer unique advantages that can be utilized for oncology applications. However, significant work is needed to understand their underlying mechanisms and develop technologies to improve their effectiveness.

The application of next-generation sequencing-based genomics and corresponding analytical pipelines have significantly improved our ability to identify tumor-unique antigenic peptides ("neoantigens") for the design of personalized vaccine therapies and to monitor immune responses to these vaccines. The more recent implementation of artificial intelligence and machine learning into several of the more complex analytical components of the neoantigen selection process has provided significant improvements across a number of previously difficult aspects within neoantigen identification, as we will describe. Related technologies and analytics have been developed that enable the characterization of changes to the tumor immune microenvironment facilitated by vaccination and monitor systemic responses in patients. Here, we review these new methods and their application to the design, implementation, and evaluation of cancer vaccines.

Recent advances in cancer immunotherapy have established neoantigen-based vaccines as a promising approach to cancer prevention. Unlike tumor-associated antigens, neoantigens originate exclusively from somatic mutations, thus enabling tumor-specific targeting without harm to normal tissues. This distinctive feature promotes robust immune responses while reducing the risk of autoimmune side effects. Developing standardized "off-the-shelf" vaccines targeting shared neoantigens offers a scalable strategy for cancer prevention, particularly benefitting genetically predisposed high-risk populations. These vaccines can be administered to high-risk individuals before malignant transformation to potentially intercept cancer development through early immune activation. Advances in next-generation sequencing and computational biology have increased the accuracy of neoantigen prediction, while advances in vaccine delivery platforms have boosted vaccine efficacy. The integration of neoantigen-based vaccines with immune checkpoint inhibitors, immune stimulants, and classic chemopreventive agents has a synergistic potential to improve cellular immunity. This review examines biological mechanisms, clinical development, and future directions of neoantigen-based vaccines in cancer prevention, emphasizing their clinical potential to revolutionize risk-reduction strategies.