Development of an mRNA-based therapeutic vaccine mHTV-03E2 for high-risk HPV-related malignancies.

Human papillomavirus (HPV) 16 and 18 infections are related to many human cancers. Despite several preventive vaccines for high-risk (hr) HPVs, there is still an urgent need to develop therapeutic HPV vaccines for targeting pre-existing hrHPV infections and lesions. In this study, we developed a lipid nanoparticle (LNP)-formulated mRNA-based HPV therapeutic vaccine (mHTV)-03E2, simultaneously targeting the E2/E6/E7 of both HPV16 and HPV18. mHTV-03E2 dramatically induced antigen-specific cellular immune responses, leading to significant CD8+ T cell infiltration and cytotoxicity in TC-1 tumors derived from primary lung epithelial cells of C57BL/6 mice expressing HPV E6/E7 antigens, mediated significant tumor regression, and prolonged animal survival, in a dose-dependent manner. We further demonstrated significant T cell immunity against HPV16/18 E6/E7 antigens for up to 4 months post-vaccination in immunological and distant tumor rechallenging experiments, suggesting robust memory T cell immunity against relapse. Finally, mHTV-03E2 synergized with immune checkpoint blockade to inhibit tumor growth and extend animal survival, indicating the potential in combination therapy. We conclude that mHTV-03E2 is an excellent candidate therapeutic mRNA vaccine for treating malignancies caused by HPV16 or HPV18 infections.

Effects of vaginal microbiota on human papillomavirus infection and its related diseases.

With the knowledge of female reproductive tract microbiota gradually increasing, the connection between vaginal microbiota (VMB) and its related diseases is increasingly highlighted. Manifestation of VMB keeps changing with various dominated bacteria, which can affect the immune response of mucosal barrier and the entrance of pathogens. Human papillomavirus (HPV), as an oncogenic virus, is closely related to viral-associated cancer, such as cervical cancer. According to HPV infection status, VMB can transform into different types, and result in accelerating or restraining the progression of diseases, which have exposed the inner link between VMB and HPV. Therefore, probiotics therapy promises to be a new complementary therapy to rebuild a healthy VMB for patients, but there's still a long way to go before its ready for the clinic. This review focuses on composition, immune response, and application of VMB in HPV and its associated diseases and aims to provide the new ideas and directions for the research on VMB.

Comparing the effects of argon plasma coagulation and interferon therapy in patients with vaginal intraepithelial neoplasia: a single-center retrospective study.

PURPOSE: This study aimed to evaluate the clinical efficacy and safety of argon plasma coagulation (APC) therapy and interferon therapy in patients with grade I and II vaginal intraepithelial neoplasia (VaIN). METHODS: A total of 112 patients with VaIN were diagnosed via colposcopy-induced biopsy and classified into the APC group (n = 77) and interferon group (n = 35). Clinical data including age, grade, symptoms, historical or concomitant neoplasia of the lower genital tract, indications for hysterectomy, pregnancy history, cytology, human papillomavirus (HPV) subtype, treatment modalities, and clinical outcomes were analyzed, retrospectively. Complications and clinical outcomes were assessed at 6- and 12-month follow-ups. RESULTS: There was no significant difference in the HPV clearance rate between the APC (53.42%) and interferon (33.33%) groups at 6 months after treatment. However, the 12-month follow-up of the APC group showed a significantly higher HPV clearance rate as compared to the interferon group (87.67% vs. 51.52%, P < 0.05). The APC group exhibited a significantly higher cure rate (79.22% vs. 40.0%) and lower persistence rate (12.99% vs. 37.14%) than the interferon group (P < 0.05). Adverse reaction analysis revealed that the primary reaction in the APC group was vaginal drainage, in contrast to the increased vaginal discharge in the interferon group; though the difference was significant (68.83% vs. 28.57%, P < 0.05), no serious complications were observed. CONCLUSIONS: Treatment with APC is a safe and more effective procedure against VaIN I and II, compared to interferon. APC may serve as a viable alternative to other physiotherapies.

The impact of distance to facility on treatment modality, short-term outcomes, and survival of patients with HPV-positive oropharyngeal squamous cell carcinoma.

PURPOSE: This study compared treatment and outcomes for patients with HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) based on their travel distance to treatment facility. MATERIALS AND METHODS: Patients with cT1-4, N0-3, M0 HPV-positive OPSCC in the National Cancer Database from 2010 to 2019 were identified and split into four quartiles based on distance to facility, with quartile 4 representing patients with furthest travel distances. Multivariable-adjusted logistic regression and Cox proportional hazards modeling were used to analyze the primary outcome of treatment received, and secondary outcomes of clinical stage, overall survival, surgical approach (i.e., TORS versus other), and 30-day surgical readmissions. RESULTS: 17,207 patients with HPV-positive OPSCC were evenly distributed into four quartiles. Compared to patients in quartile 1, patients in quartile 4 were 40 % less likely to receive radiation versus surgery (OR = 0.60; 95 % CI = 0.54-0.66). Among the patients who received surgery, quartile 4 had a higher odds of receiving TORS treatment compared to quartile 1 (4v1: OR = 2.38; 95 % CI = 2.05-2.77), quartile 2 (4v2: OR = 2.31, 95 % CI = 2.00-2.66), and quartile 3 (4v3: OR = 1.75; 95 % CI = 1.54-1.99). Quartile 4 had a decreased odds of mortality compared to Quartile 1 (4v1: OR = 0.87; 95 % CI = 0.79-0.97). There were no differences among the quartiles in presenting stage and 30-day readmissions. CONCLUSIONS: This study found that patients with furthest travel distance to facility were more often treated surgically over non-surgical management, with TORS over open surgery, and had better overall survival. These findings highlight potential disparities in access to care for patients with HPV-positive OPSCC.

Overall survival, disease-free survival and quality of life in patients affected by HPV mediated p16+ oropharyngeal squamous cell carcinoma treated with upfront trans-oral robotic surgery vs radiotherapy or chemoradiotherapy.

PURPOSE: Treatment de-intensification for p16 + oropharyngeal squamous cell carcinoma (OPSCC) is an area of active research to reduce the side effects and improve patients' quality of life (QoL). In this paper we evaluated the Overall Survival (OS), the Disease-Free Survival (DFS) and the QoL of patients affected by p16 + OPSCC according to their prognostic stage group (PSG) and different treatments. METHODS: Patients were selected retrospectively through our Electronic Tumor Board Database according to prespecified inclusion criteria. Basic data of eligible patients were recorded and analyzed. Then, OS and DFS were evaluated according to the PSG and the treatments performed. Patients alive completed three questionnaires: the QoL Questionnaire Core 30 (QLQ-C30), the QoL Questionnaire Head & Neck 43 (QLQ-HN43) and the MD Anderson Dysphagia Inventory (MDADI) questionnaire. RESULTS: Sixty-one patients were included in this study. Eight patients died from the disease and the remaining 53 patients completed the 3 questionnaires. Fifteen (25%) patients were treated with upfront surgery, 6 (10%) patients with definitive radiotherapy and 40 (65%) patients with concomitant chemoradiotherapy. Comparing the DFS and the OS of PSG I patients by the different treatments performed, no statistically significant difference was identified. Patients treated with upfront surgery showed better outcomes in some aspects of their QoL. CONCLUSION: For p16 + OPSCC PSG I patients, upfront surgery can be considered a valid alternative to radiotherapy or chemoradiotherapy while maintaining a comparable DFS and OS and giving patients better results in terms of specific aspects of their QoL.

A Scoping Review of Complementary and Alternative Medicine for Human Papillomavirus Infections and Cervical Dysplasia.

OBJECTIVE: The goal of this scoping review is to synthesize clinically relevant scientific literature on current complementary and alternative medications that address human papillomavirus (HPV) infections and cervical dysplasia. MATERIALS AND METHODS: A systematic search of published studies was performed December 2021 for the following concepts: human papilloma virus, cervical dysplasia, and complementary and alternative medicine (CAM). Relevant publications were identified by searching Ovid MEDLINE ALL, Embase, Cochrane Library, AMED, and MEDLINE databases, in addition to clinical trial databases. Data were extracted based on specific study selection criteria and analyzed by 3 authors independently using Covidence software. RESULTS: A total of 2324 studies were identified of which 56 met inclusion criteria. Treatment outcomes measured regression of HPV, improvement of cervical cytology, and/or regression of histopathology with varied definitions of success across all studies. The CAM therapies found to have the most clinical benefit and best supporting data via randomized control trials were topical mushroom ( Coriolus versicolor) gel, oral and topical selenium therapies, and oral indol-3-carbinol. Adverse events were reported in only 28/56 (50%) of included studies. CONCLUSIONS: The evidence for treating HPV and cervical dysplasia with CAM is of low quality because of lack of standardized, clinically relevant treatment outcomes, lack of standardization of products, and minimal reporting on adverse and long-term effects. Future large, randomized control trials are needed to further assess efficacy and safety of CAM therapies to address HPV and cervical dysplasia.

Management of Oral Manifestations of Herpes Simplex Virus, Varicella Zoster Virus, and Human Papillomavirus.

Human herpes virus is a family of DNA viruses that includes herpes simplex virus (HSV) and varicella zoster virus (VZV). HSV-1 and HSV-2 are fairly common and result in oral and genital lesions. Recurrent infections of herpes include lesions on the lips resulting in pain and possibly societal stigma, making adequate treatment of these conditions crucial. VZV is the cause of chicken pox and shingles. Acyclovir and other nucleoside analogues have been the gold standard of treatment for HSV and VZV, but newer, more effective treatments are being developed, which is beneficial regarding the issue of resistance to standard antivirals. Human papillomavirus (HPV) is also a DNA virus with different subtypes that result in four common oral benign lesions. The significance and treatments of HSV, VZV, and HPV are discussed, along with certain developing treatments of herpes labialis (HSV).

Immunotherapy that leverages HPV-specific immune responses for precancer lesions of cervical cancer.

Cervical cancer and its precursor lesion, cervical intraepithelial neoplasia (CIN), are caused by high-risk human papillomavirus (HPV) viral infection and are highly susceptible to host immunity targeting of HPV viral proteins, which include both foreign antigens and cancer antigens expressed by tumors. Immunotherapy that induces Th1 immunoreactivity against viral proteins is expected to take advantage of this immunological regression mechanism. However, although cancer immunotherapies for cervical cancer and CIN have been developed over the past several decades, none have been commercialized. Most of these immunotherapies target the viral cancer proteins E6 and E7, which are generally the same. The reasons for the underdevelopment of HPV-targeted immunotherapy differ depending on whether the target is invasive cancer or CIN. We here summarize the developmental history of cancer immunotherapy for CIN and discuss strategies for solving the problems that led to this underdevelopment. We note that CIN is a mucosal lesion and propose that inducing mucosal immunity may be the key.

British association for sexual health and HIV national guideline for the management of anogenital warts in adults (2024).

This guideline offers recommendations on the diagnosis, treatment and health promotion principles needed for the effective management of human papillomavirus (HPV)-related warts at anogenital sites including the external genitals, vagina, cervix, urethra, perianus and anal canal. The guideline is aimed primarily at patients aged 16 years or older presenting to healthcare professionals working in level 3 sexual health services in the United Kingdom. However, the principles of the recommendations may be applied in other care settings, including in primary care, using locally adapted care pathways where appropriate. The management of HPV-related anogenital dysplasia or warts at other extragenital sites is outside the scope of this guideline.

Effectiveness of vaginal probiotics Lactobacillus crispatus chen-01 in women with high-risk HPV infection: a prospective controlled pilot study.

Female genital tract infection with high-risk human papilloma virus (HR-HPV) has the risk of developing into cervical cancer, and there is still a lack of effective therapeutic strategies. Probiotic intervention is considered as a potential intervention for HR-HPV, while exploration into living probiotic preparations for specific diseases remains limited and insufficient. This prospective controlled pilot study was conducted to observe the effect of intravaginal transplantation of a vaginal isolated natural probiotic strain, Lactobacillus crispatus chen-01, on the clearance of high-risk HPV infection. 100 women with high-risk HPV infection were enrolled and randomly divided into placebo group and probiotic treatment group, which received intravaginal transplantation of L. crispatus chen-01. Cervical exfoliated cells were collected 6 months later for detecting DNA load, typing of HPV, and cytological analysis. Our results showed that vaginal transplantation with L. crispatus chen-01 significantly reduced viral load of HPV, ameliorated HPV clearance rate, and improved vaginal inflammation state without causing obvious adverse reactions. Analysis of 16S rRNA sequencing revealed that L. crispatus chen-01 could effectively reconstitute the vaginal microbiota in women with high-risk HPV, which might be one of the underlying mechanisms of the beneficial effect of L. crispatus chen-01 transplantation. Our results suggested that vaginal transplantation of L. crispatus chen-01 might be a promising treatment for patients with high-risk HPV infection.

Three-dimensional chromatin analysis reveals Sp1 as a mediator to program and reprogram HPV-host epigenetic architecture in cervical cancer.

Human papillomavirus (HPV) is predominantly associated with HPV-related cancers, however, the precise mechanisms underlying the HPV-host epigenetic architectures in HPV carcinogenesis remain elusive. Here, we employed high-throughput chromosome conformation capture (Hi-C) to comprehensively map HPV16/18-host chromatin interactions. Our study identified the transcription factor Sp1 as a pivotal mediator in programming HPV-host interactions. By targeting Sp1, the active histone modifications (H3K27ac, H3K4me1, and H3K4me3) and the HPV-host chromatin interactions are reprogrammed, which leads to the downregulation of oncogenes located near the integration sites in both HPV (E6/E7) and the host genome (KLF5/MYC). Additionally, Sp1 inhibition led to the upregulation of immune checkpoint genes by reprogramming histone modifications in host cells. Notably, humanized patient-derived xenograft (PDX-HuHSC-NSG) models demonstrated that Sp1 inhibition promoted anti-PD-1 immunotherapy via remodeling the tumor immune microenvironment in cervical cancer. Moreover, single-cell transcriptomic analysis validated the enrichment of transcription factor Sp1 in epithelial cells of cervical cancer. In summary, our findings elucidate Sp1 as a key mediator involved in the programming and reprogramming of HPV-host epigenetic architecture. Inhibiting Sp1 with plicamycin may represent a promising therapeutic option for HPV-related carcinoma.

Mapping the research landscape of HPV-positive oropharyngeal cancer: a bibliometric analysis.

OBJECTIVE: The aim of the study is to evaluate the scientific interest, the collaboration patterns and the emerging trends regarding HPV+ OPSCC diagnosis and treatment. MATERIALS AND METHODS: A cross-sectional bibliometric analysis of articles reporting on HPV+ OPSCC within Scopus database was performed and all documents published up to December 31th, 2022 were eligible for analysis. Outcomes included the exploration of key characteristics (number of manuscripts published per year, growth rate, top productive countries, most highly cited papers, and the most well-represented journals), collaboration parameters (international collaboration ratio and networks, co-occurrence networks), keywords analysis (trend topics, factorial analysis). RESULTS: A total of 5200 documents were found, published from March, 1987 to December, 2022. The number of publications increased annually with an average growth rate of 19.94%, reaching a peak of 680 documents published in 2021. The 10 most cited documents (range 1105-4645) were published from 2000 to 2012. The keywords factorial analysis revealed two main clusters: one on epidemiology, diagnosis, prevention and association with other HPV tumors; the other one about the therapeutic options. According to the frequency of keywords, new items are emerging in the last three years regarding the application of Artifical Intelligence (machine learning and radiomics) and the diagnostic biomarkers (circulating tumor DNA). CONCLUSIONS: This bibliometric analysis highlights the importance of research efforts in prevention, diagnostics, and treatment strategies for this disease. Given the urgency of optimizing treatment and improving clinical outcomes, further clinical trials are needed to bridge unaddressed gaps in the management of HPV+ OPSCC patients.

A comparison of timing and patterns of treatment failure, and survival outcomes after progression between HPV+ and HPV- patients undergoing chemoradiation for oropharyngeal squamous cell carcinomas.

BACKGROUND: We aimed to analyze and compare the timing and patterns of treatment failure, and survival after progression between HPV-positive (HPV+) and HPV-negative (HPV-) patients undergoing chemoradiation for oropharyngeal squamous cell carcinomas (OPSCC). METHODS: A retrospective review was performed of all patients undergoing primary chemoradiation for OPSCC between 2008 and 2021. Demographic and clinical data were collected. Kaplan-Meier estimates for overall survival (OS), and time to recurrence/metastases (TTR) were compared using the log-rank test, with Cox regression used for multivariable modeling comparing HPV+ and HPV- patients. RESULTS: HPV- patients developed recurrence or metastases at earlier time points than HPV+ patients (8.8 vs. 15.2 months, p < 0.05), due to earlier local/locoregional recurrence and distant metastases, but not isolated regional recurrences. HPV- distant metastases exclusively occurred in a single organ, most commonly the lungs or bone, while HPV+ metastases frequently had multi-organ involvement in a wide variety of locations (p < 0.05). Once progression (recurrence/metastases) was diagnosed, HPV+ patients experienced superior survival to HPV- patients on univariate and multivariate analysis, largely due to improved outcomes after treatment of local/locoregional recurrences (p < 0.05). There were no differences in survival after isolated regional recurrences or distant metastases. CONCLUSION: HPV+ OPSCC patients relapse later compared to HPV- patients in local/locoregional and distant sites. HPV+ patients with local/locoregional recurrence experience superior survival after recurrence, which does not hold true for isolated regional recurrences or distant metastases. These data can be useful to inform prognosis and guide treatment decisions in patients with recurrent OPSCC.

Hypoxia-Directed Treatment of Human Papillomavirus-Related Oropharyngeal Carcinoma.

PURPOSE: Standard curative-intent chemoradiotherapy for human papillomavirus (HPV)-related oropharyngeal carcinoma results in significant toxicity. Since hypoxic tumors are radioresistant, we posited that the aerobic state of a tumor could identify patients eligible for de-escalation of chemoradiotherapy while maintaining treatment efficacy. METHODS: We enrolled patients with HPV-related oropharyngeal carcinoma to receive de-escalated definitive chemoradiotherapy in a phase II study (ClinicalTrials.gov identifier: NCT03323463). Patients first underwent surgical removal of disease at their primary site, but not of gross disease in the neck. A baseline 18F-fluoromisonidazole positron emission tomography scan was used to measure tumor hypoxia and was repeated 1-2 weeks intratreatment. Patients with nonhypoxic tumors received 30 Gy (3 weeks) with chemotherapy, whereas those with hypoxic tumors received standard chemoradiotherapy to 70 Gy (7 weeks). The primary objective was achieving a 2-year locoregional control (LRC) of 95% with a 7% noninferiority margin. RESULTS: One hundred fifty-eight patients with T0-2/N1-N2c were enrolled, of which 152 patients were eligible for analyses. Of these, 128 patients met criteria for 30 Gy and 24 patients received 70 Gy. The 2-year LRC was 94.7% (95% CI, 89.8 to 97.7), meeting our primary objective. With a median follow-up time of 38.3 (range, 22.1-58.4) months, the 2-year progression-free survival (PFS) and overall survival (OS) rates were 94% and 100%, respectively, for the 30-Gy cohort. The 70-Gy cohort had similar 2-year PFS and OS rates at 96% and 96%, respectively. Acute grade 3-4 adverse events were more common in 70 Gy versus 30 Gy (58.3% v 32%; P = .02). Late grade 3-4 adverse events only occurred in the 70-Gy cohort, in which 4.5% complained of late dysphagia. CONCLUSION: Tumor hypoxia is a promising approach to direct dosing of curative-intent chemoradiotherapy for HPV-related carcinomas with preserved efficacy and substantially reduced toxicity that requires further investigation.

Identification of HPV-E7 specific TCRs for tumor immunotherapy.

The oncogenic protein E7 of the Human Papillomavirus (HPV) is constitutionally expressed in HPV-associated tumors and has the potential to be targeted in T cell receptor (TCR)-based immunotherapy. Adoptive transfer of TCR-engineered T (TCR-T) cells has shown promise as a therapeutic approach for HPV-induced tumors. This study aimed to identify HPV-E7 specific TCRs from HLA-A11:01 transgenic mice through single-cell sorting and sequencing facilitated by E789-97/HLA-A11:01 tetramer. Two dominant TCRs were identified, which exhibited specific binding to E789-97 presented in the context of HLA-A*11:01. TCR-T cells were prepared by infecting primary T cells with lentiviruses containing the TCR genes, and the two TCRs demonstrated substantial responsiveness and showed CD8+ dependent cytokine secretion characteristics. Further analyses of the cytokine profiles revealed that the two TCRs were capable of exerting polyfunctional responses upon specific stimulation. These findings suggest that the two TCRs represent promising candidates for the development of future therapeutic drugs targeting HPV-E7 in the context of HLA-A*11:01 for tumor immunotherapy.

Unveiling the multifaceted realm of human papillomavirus: a comprehensive exploration of biology, interactions, and advances in cancer management.

Human Papillomavirus (HPV), an extensive family of DNA viruses, manifests as a persistent global health challenge. Persistent HPV infection is now firmly established as a significant aetiological factor for a spectrum of malignancies. In this review, we examine the latest insights into HPV biology and its intricate relationship with the host. We delve into the complex dynamics of co-infections involving HPV alongside other viruses, such as HIV, EBV, and HSV, as well as the burgeoning role of the microbiome in cancer development. We also explore recent advancements in understanding the specific contributions of HPV in the development of various cancers, encompassing cancers of the anogenital region, head and neck, as well as breast, lung, and prostate. Moreover, we focus on the current preventive strategies, including vaccination and screening methods, and therapeutic interventions that range from traditional approaches like surgery and chemotherapy to emerging modalities such as targeted therapies and immunotherapies. Additionally, we provide a forward-looking view on the future directions of HPV research, highlighting potential areas of exploration to further our understanding and management of HPV and its associated cancers. Collectively, this review is positioned to deepen readers' understanding of HPV biology and its complex interplay with cancer biology. It presents innovative strategies for the prevention, management, and therapeutic intervention of HPV-associated malignancies.

Definitive radio(chemo)therapy versus upfront surgery in the treatment of HPV-related localized or locally advanced oropharyngeal squamous cell carcinoma.

BACKGROUND: The treatment of stage I-III HPV+ oropharyngeal squamous cell carcinoma (HPV-OPSCC) is based on either surgery ± adjuvant therapy or exclusive radio±chemotherapy. We sought to compare these two therapeutic strategies in terms of efficacy, tolerance and quality of life (QoL). METHODS: Patients treated for stage I-III HPV-OPSCC from 2010 to 2021 in 3 academic centers were included and sorted according to the treatment strategy: surgery or exclusive radio±chemotherapy. Efficacy and tolerance were retrospectively assessed, and a transversal exploratory QoL assessment was performed using QoL instruments. RESULTS: A total of 83 patients were included, with 21 undergoing non-minimally invasive surgery and 62 receiving definitive radio-±chemotherapy. 2-year progression-free survival (PFS) and overall survival (OS) were respectively 80% and 86% in the surgical group and 92% and 95% in the non-surgical group, with no significant difference. At the end of treatment, 64.5% of patients presented with a grade III toxicity, without significant difference between the two groups. No patient had late grade III toxicity at 24 months. Forty-five patients (11 in the surgical group, 34 in the non-surgical group) participated in an exploratory quality-of-life analysis. Patients reported significantly more fatigue and loss of appetite after surgery, whereas patients in the radio±chemotherapy group described significantly more salivary and oral problems and difficulty swallowing, but the median time between treatment completion and the response to the questionnaires. CONCLUSION: There was no significant difference in efficacy, physician-reported toxicity and overall patient-reported quality of life was found between non-minimally invasive surgery and radio±chemotherapy in the treatment of stage I-III HPV-OPSCC.

De-Escalated Therapy and Early Treatment of Recurrences in HPV-Associated Head and Neck Cancer: The Potential for Biomarkers to Revolutionize Personalized Therapy.

Human papillomavirus-associated (HPV+) head and neck squamous cell carcinoma (HNSCC) is the most common HPV-associated cancer in the United States, with a rapid increase in incidence over the last two decades. The burden of HPV+ HNSCC is likely to continue to rise, and given the long latency between infection and the development of HPV+ HNSCC, it is estimated that the effect of the HPV vaccine will not be reflected in HNSCC prevalence until 2060. Efforts have begun to decrease morbidity of standard therapies for this disease, and its improved characterization is being leveraged to identify and target molecular vulnerabilities. Companion biomarkers for new therapies will identify responsive tumors. A more basic understanding of two mechanisms of HPV carcinogenesis in the head and neck has identified subtypes of HPV+ HNSCC that correlate with different carcinogenic programs and that identify tumors with good or poor prognosis. Current development of biomarkers that reliably identify these two subtypes, as well as biomarkers that can detect recurrent disease at an earlier time, will have immediate clinical application.

Nonpersistent Nanoarchitectures Enhance Concurrent Chemoradiotherapy in an Immunocompetent Orthotopic Model of HPV+ Head/Neck Carcinoma.

Cisplatin chemoradiotherapy (CRT) is the established standard of care for managing locally advanced human papillomavirus-positive head/neck carcinoma. The typically young patients may suffer serious and long-time side effects caused by the treatment, such as dysphagia, and hearing loss. Thus, ensuring a satisfactory post-treatment quality of life is paramount. One potential replacing approach to the classical CRT involves the combination of standard-dose radiotherapy and radiosensitizers such as noble metal nanoparticles (NPs). However, several concerns about size, shape, and biocompatibility limit the translation of metal nanomaterials to the clinical practice. Here, it is demonstrated that a new model of nonpersistent gold nanoarchitectures containing cisplatin (NAs-Cluster-CisPt) generates, in combination with radiotherapy, a significant in vivo tumor-reducing effect compared to the standard CRT, achieving a complete tumor clearance in 25% of the immunocompetent models that persist for 60 days. These findings, together with the negligible amount of metals recognized in the excretory organs, highlight that the concurrent administration of NAs-Cluster-CisPt and radiotherapy has the potential to overcome some clinical limitations associated to NP-based approaches while enhancing the treatment outcome with respect to standard CRT. Overall, despite further mechanistic investigations being essential, these data support the exploiting of nonpersistent metal-nanomaterial-mediated approaches for oral cancer management.

The HPV viral regulatory mechanism of TLRs and the related treatments for HPV-associated cancers.

Infection with human papillomavirus (HPV) typically leads to cervical cancer, skin related cancers and many other tumors. HPV is mainly responsible for evading immune tumor monitoring in HPV related cancers. Toll like receptors (TLRs) are particular pattern recognition molecules. When the body is facing immune danger, it can lead to innate and direct adaptive immunity. TLR plays an important role in initiating antiviral immune responses. HPV can affect the expression level of TLR and interfere with TLR related signaling pathways, resulting in sustained viral infection and even carcinogenesis. This paper introduces the HPV virus and HPV related cancers. We discussed the present comprehension of TLR, its expression and signaling, as well as its role in HPV infection. We also provided a detailed introduction to immunotherapy methods for HPV related diseases based on TLR agonists. This will provide insights into methods that support the therapeutic method of HPV related conditions with TLR agonists.