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Search Results (453)

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Keywords = Oropharyngeal cancer

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11 pages, 421 KiB  
Article
Integrating Dentists into HPV Vaccine Promotion: A Cross-Sectional Study in a Dental Academic Institution to Address Gaps in Oral and General Health
by David Lee, Anita Joy-Thomas, Gisela Bona, Gregory Olson, Alice Pazmino, Lubna Fawad and Ana Neumann
Appl. Sci. 2025, 15(15), 8262; https://doi.org/10.3390/app15158262 - 25 Jul 2025
Viewed by 254
Abstract
(1) Background: Human Papillomavirus (HPV)-associated oropharyngeal cancer is the fastest-growing head and neck malignancy, yet vaccination coverage remains suboptimal. (2) Methods: In this cross-sectional survey conducted from April 2022 to April 2023, 400 parents of patients aged 8–18 years (mean ± SD = [...] Read more.
(1) Background: Human Papillomavirus (HPV)-associated oropharyngeal cancer is the fastest-growing head and neck malignancy, yet vaccination coverage remains suboptimal. (2) Methods: In this cross-sectional survey conducted from April 2022 to April 2023, 400 parents of patients aged 8–18 years (mean ± SD = 12.8 ± 2.6; 59.3% female) reported their child’s HPV vaccination status and willingness to initiate or complete the vaccine series at a dental clinic. For those who were not fully vaccinated, reasons for refusal were documented. (3) Results: Over half (54.5%, n = 218) of the children were not fully vaccinated. Notably, 21% (46/218) of parents indicated an immediate willingness to vaccinate their child if the dentist offered it—a significant potential for improvement compared to general healthcare settings. Reported barriers included preference for a physician’s office (43.6%), indecision (20.3%), unspecified concerns (14.5%), safety worries (8.1%), and religious objections (5.2%). Male and younger patients (9–11 years) showed significantly lower vaccination coverage (p < 0.05). (4) Conclusions: Dentists can substantially impact public health by integrating immunization counseling, interprofessional collaboration, and vaccine administration, thereby addressing critical gaps in HPV-related cancer prevention. These findings highlight the opportunity for dental offices to enhance vaccination rates and prompt further research, education, and policy initiatives to advance the oral and general health of our patients. Full article
(This article belongs to the Special Issue New Challenges in Dentistry and Oral Health)
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19 pages, 663 KiB  
Review
Association Between Diabetes Mellitus and Head and Neck Cancer: An Umbrella Review of Systematic Reviews and Meta-Analyses
by Filipa Formosinho, Alexandra Arcanjo and Maria Conceição Manso
Oral 2025, 5(3), 52; https://doi.org/10.3390/oral5030052 - 24 Jul 2025
Viewed by 1232
Abstract
Background/Objectives: Emerging evidence links diabetes to increased cancer risk. This study aimed to assess the association between diabetes mellitus (DM)(type 1, type 2, or gestational) and the development of head and neck cancer. Methods: An umbrella review was conducted using systematic searches in [...] Read more.
Background/Objectives: Emerging evidence links diabetes to increased cancer risk. This study aimed to assess the association between diabetes mellitus (DM)(type 1, type 2, or gestational) and the development of head and neck cancer. Methods: An umbrella review was conducted using systematic searches in Cochrane, EBSCO, Wiley, ScienceDirect, and PubMed (January 2000–January 2024), registered in PROSPERO (CRD42024512151). Included were systematic reviews (SRs) and meta-analyses (MAs) of observational studies. Article selection followed the PRISMA guidelines; the quality and risk of bias of the selected studies were assessed with the Joanna Briggs Institute Checklist. The GROOVE tool was used to identify double counting. Two independent reviewers screened studies, with a third resolving disagreements. Results: Seven SRs were included. While DM has been widely examined in cancer research, few studies specifically targeted head and neck cancers. Of the 20 associations between various cancer sites and diabetes types, 9 (45%) showed a statistically significant positive correlation. The strongest evidence was for overall cancer risk (RR = 1.22, 95% CI: 1.16–1.29, p < 0.001). Oral cancer showed elevated risks (RRR = 1.13, p = 0.009; OR = 1.32, p < 0.001; HR = 1.73, p < 0.05; RR = 1.28, p < 0.05). Increased risks were also observed for oropharyngeal (RR = 1.18; HR = 1.53), head and neck (HR = 1.47), and nasopharyngeal cancer (OR = 1.40), all p < 0.05. Heterogeneity was low in two reviews, unreported in one, and high in four. Five SRs reported associated risk factors. Conclusions: While some associations between DM and cancer appear significant, evidence remains limited and inconsistent, particularly for oral cancer. Further standardized, high-quality research is needed to clarify the link across head and neck cancer subtypes. Full article
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13 pages, 3313 KiB  
Article
CT Texture Patterns Reflect HPV Status but Not Histological Differentiation in Oropharyngeal Squamous Cell Carcinoma
by Lays Assolini Pinheiro de Oliveira, Caio Elias Irajaya Lobo Peresi, Daniel Vitor Aguiar Nozaki, Ericka Francislaine Dias Costa, Lana Ferreira Santos, Carmen Silvia Passos Lima, Sérgio Lúcio Pereira de Castro Lopes and Andre Luiz Ferreira Costa
Cancers 2025, 17(14), 2317; https://doi.org/10.3390/cancers17142317 - 11 Jul 2025
Viewed by 364
Abstract
Background: Texture analysis (TA) has shown promise in characterizing intratumoral heterogeneity from imaging data. We add to the literature that shows its capability to differentiate oropharyngeal cancers based on HPV status. Methods: Multislice CT analysis was done in 120 patients with confirmed OP [...] Read more.
Background: Texture analysis (TA) has shown promise in characterizing intratumoral heterogeneity from imaging data. We add to the literature that shows its capability to differentiate oropharyngeal cancers based on HPV status. Methods: Multislice CT analysis was done in 120 patients with confirmed OP SCC: a single 5 mm region of interest was placed on three consecutive homogeneous CT slices per patient. Texture features were extracted by using gray-level co-occurrence matrices averaged per patient. HPV status (via p16 IHC and molecular confirmation) and differentiation grade (i.e., good, moderate, and poor) were recorded. Non-parametric statistical tests assessed differences between subgroups. Results: Seven texture parameters (i.e., angular second moment, contrast, sum of squares, sum entropy, entropy, inverse difference moment, and difference variance) differed significantly between HPV+ and HPV− tumors (all p < 0.05). HPV+ tumors exhibited increased heterogeneity and complexity on CT imaging. No texture feature correlated with histological grade. Conclusions: This study adds to the growing evidence that CT-based TA can assess HPV status in OP SCC. TA may be promising, though it requires further validation as an adjunctive method integrating into radiomics workflows to develop predictive models for diagnosis, prognosis, and treatment planning. Full article
(This article belongs to the Collection Imaging Biomarker in Oncology)
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24 pages, 312 KiB  
Article
Social Ecological Influences on HPV Vaccination Among Cape Verdean Immigrants in the U. S.: A Qualitative Study
by Ana Cristina Lindsay, Celestina V. Antunes, Aysha G. Pires, Monica Pereira and Denise L. Nogueira
Vaccines 2025, 13(7), 713; https://doi.org/10.3390/vaccines13070713 - 30 Jun 2025
Viewed by 428
Abstract
Background: Human papillomavirus (HPV) is the most common sexually transmitted infection in the United States (U.S.) and a major contributor to several cancers, including cervical, anal, penile, and oropharyngeal cancers. Although a safe and effective vaccine is available, HPV vaccination rates remain suboptimal, [...] Read more.
Background: Human papillomavirus (HPV) is the most common sexually transmitted infection in the United States (U.S.) and a major contributor to several cancers, including cervical, anal, penile, and oropharyngeal cancers. Although a safe and effective vaccine is available, HPV vaccination rates remain suboptimal, particularly among racial, ethnic, and immigrant minority groups. This study explored multiple factors, such as cultural, social, and structural influences, influencing HPV vaccine decision-making among Cape Verdean immigrant parents in the U.S., a population currently underrepresented in HPV research. Methods: Qualitative study using individual, in-depth interviews with Cape Verdean immigrant parents of children aged 11 to 17 years living in the U.S. Interviews were transcribed verbatim and analyzed thematically using the social ecological model (SEM) to identify barriers and facilitators at the intrapersonal, interpersonal, organizational, community, and policy levels. Results: Forty-five Cape Verdean parents (27 mothers, 18 fathers) participated. Fathers were significantly older than mothers (50.0 vs. 41.1 years, p = 0.05). Most were married or partnered (60%), had at least a high school education (84.4%), and reported annual household incomes of US$50,000 or more (66.7%), with no significant gender differences. Nearly all spoke Creole at home (95.6%). Fathers had lower acculturation than mothers (p = 0.05), reflecting less adaptation to U.S. norms and language use. Most parents had limited knowledge of HPV and the vaccine, with gendered beliefs and misconceptions about risk. Only seven mothers (25.9%) reported receiving a provider recommendation; all indicated that their children had initiated vaccination (1 dose or more). Mothers were the primary decision-makers, though joint decision-making was common. Trust in providers was high, but poor communication and the lack of culturally and linguistically appropriate materials limited informed decision-making. Stigma, misinformation, and cultural taboos restricted open dialogue. Trusted sources of information included schools, churches, and Cape Verdean organizations. While parents valued the U.S. healthcare system, they noted gaps in public health messaging and provider engagement. Conclusions: Findings revealed that HPV vaccine uptake and hesitancy among Cape Verdean immigrant parents in the U.S. were influenced by individual beliefs, family dynamics, healthcare provider interactions, cultural norms, and structural barriers. These findings highlight the need for multilevel strategies such as culturally tailored education, community engagement, and improved provider communication to support informed vaccination decisions in this population. Full article
(This article belongs to the Special Issue Vaccine Strategies for HPV-Related Cancers: 2nd Edition)
33 pages, 519 KiB  
Systematic Review
Impact of Oncological Treatment on Quality of Life in Patients with Head and Neck Malignancies: A Systematic Literature Review (2020–2025)
by Raluca Grigore, Paula Luiza Bejenaru, Gloria Simona Berteșteanu, Ruxandra Ioana Nedelcu-Stancalie, Teodora Elena Schipor-Diaconu, Simona Andreea Rujan, Bianca Petra Taher, Șerban Vifor Gabriel Berteșteanu, Bogdan Popescu, Irina Doinița Popescu, Alexandru Nicolaescu, Anca Ionela Cîrstea and Catrinel Beatrice Simion-Antonie
Curr. Oncol. 2025, 32(7), 379; https://doi.org/10.3390/curroncol32070379 - 30 Jun 2025
Viewed by 489
Abstract
Background: Quality of life (QoL) is a critical indicator in assessing the success of oncological treatments for head and neck malignancies, reflecting their impact on physiological functions and psychosocial well-being beyond mere survival. Treatments (surgery, radiotherapy, chemotherapy) pose multiple functional and emotional [...] Read more.
Background: Quality of life (QoL) is a critical indicator in assessing the success of oncological treatments for head and neck malignancies, reflecting their impact on physiological functions and psychosocial well-being beyond mere survival. Treatments (surgery, radiotherapy, chemotherapy) pose multiple functional and emotional challenges, and recent advancements underscore the necessity of evaluating post-treatment QoL. Objective: This literature review investigates the impact of oncological treatment on the QoL of patients with malignant head and neck cancers (oral, oropharyngeal, hypopharyngeal, laryngeal) and identifies factors influencing their QoL index. Methodology: Using a PICO framework, studies from PubMed Central were analyzed, selected based on inclusion (English publications, full text, PROM results) and exclusion criteria. The last research was conducted on 6 April 2025. From 231 identified studies, 49 were included after applying filters (MeSH: “Quality of Life,” “laryngeal cancer,” “oral cavity cancer,” etc.). Data were organized in Excel, and the methodology adhered to PRISMA standards. Results: Treatment Impact: Oncological treatments significantly affect QoL, with acute post-treatment declines in functions such as speech, swallowing, and emotional well-being (anxiety, depression). Partial recovery depends on rehabilitative interventions. Influencing Factors: Treatment type, disease stage, socioeconomic, and demographic contexts influence QoL. De-escalated treatments and prompt rehabilitation improve recovery, while complications like trismus, dysphagia, or persistent hearing issues reduce long-term QoL. Assessment Tools: Standardized PROM questionnaires (EORTC QLQ-C30, QLQ-H&N35, MDADI, HADS) highlighted QoL variations. Studies from Europe, North America, and Asia indicate regional differences in outcomes. Limitations: Retrospective designs, small sample sizes, and PROM variability limit generalizability. Multicentric studies with extended follow-up are recommended. Conclusions: Oncological treatments for head and neck malignancies have a complex impact on QoL, necessitating personalized and multidisciplinary strategies. De-escalated therapies, early rehabilitation, and continuous monitoring are essential for optimizing functional and psychosocial outcomes. Methodological gaps highlight the need for standardized research. Full article
(This article belongs to the Section Head and Neck Oncology)
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21 pages, 1081 KiB  
Article
HPV Knowledge, Vaccination Uptake, and Salivary Diagnostics Among Dental Students in Romania
by Sergiu Baranga, Doina Chioran, Octavia Balean, Ramona Dumitrescu, Roxana Popescu, Daniela Jumanca, Roxana Oancea, Ruxandra Sava-Rosianu, Vanessa Bolchis and Atena Galuscan
Vaccines 2025, 13(6), 658; https://doi.org/10.3390/vaccines13060658 - 19 Jun 2025
Viewed by 653
Abstract
Background: Human papillomavirus (HPV) is a key cause of cervical and oropharyngeal cancers. Despite available vaccines, uptake remains low in Romania due to limited awareness and hesitancy. This study assessed HPV knowledge, vaccination status, and the presence of high-risk strains (16 and 18) [...] Read more.
Background: Human papillomavirus (HPV) is a key cause of cervical and oropharyngeal cancers. Despite available vaccines, uptake remains low in Romania due to limited awareness and hesitancy. This study assessed HPV knowledge, vaccination status, and the presence of high-risk strains (16 and 18) in the saliva of dental students from Victor Babeș University in Timișoara. Methods: A cross-sectional study was conducted between February and March 2024, enrolling 199 dental students. Participants completed a 15-item questionnaire addressing HPV-related knowledge, vaccination status, lifestyle factors, and health history. Saliva samples were collected and analyzed using real-time PCR for the detection of HPV types 16 and 18. Logistic regression analysis was employed to identify predictors of vaccination uptake. Results: Only 10.6% of participants had received the HPV vaccine, although 96.9% acknowledged its safety and efficacy. Awareness was higher among females (88.1%) than males (84.3%), and vaccination rates were significantly greater among students under 25 years old (p = 0.0312). A total of 16.6% reported the presence of papillomas or warts. HPV DNA was detected in 10% of saliva samples. Conclusions: Although awareness of HPV was high, vaccination rates remained low, revealing a gap between knowledge and preventive action. Saliva-based screening shows promise as a non-invasive diagnostic tool, and integrating targeted education and advocacy into dental curricula may enhance public health outcomes in Romania. Full article
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12 pages, 719 KiB  
Review
Understanding HPV-Induced Cancers and Investigating the Barriers Faced by Low- and Middle-Income Countries in Prevention and Treatment
by Zahab N. Aleezada, Ishika Patel and Nabiha Yusuf
Int. J. Mol. Sci. 2025, 26(12), 5581; https://doi.org/10.3390/ijms26125581 - 11 Jun 2025
Viewed by 658
Abstract
Human papillomavirus (HPV) is a leading cause of several cancers, most notably cervical cancer, but also anal, penile, vulvar, vaginal, and oropharyngeal malignancies. While vaccines and screening technologies offer highly effective prevention, the global burden of HPV-induced cancers remains disproportionately high in low- [...] Read more.
Human papillomavirus (HPV) is a leading cause of several cancers, most notably cervical cancer, but also anal, penile, vulvar, vaginal, and oropharyngeal malignancies. While vaccines and screening technologies offer highly effective prevention, the global burden of HPV-induced cancers remains disproportionately high in low- and middle-income countries (LMICs). This literature review provides a comprehensive synthesis of the types, mechanisms, treatments, and prevention strategies associated with HPV-related cancers, while also highlighting regional disparities in healthcare access and infrastructure. It critically examines the barriers LMICs face in adopting life-saving interventions, such as limited healthcare infrastructure, vaccine hesitancy, funding gaps, and cultural stigma. The review further explores recent scientific and policy advances—including single-dose vaccination, self-sampling HPV tests, and senolytic therapies—that have the potential to reduce global health inequities. By connecting molecular biology with public health systems, this paper underscores the need for interdisciplinary solutions and equity-centered approaches to combat HPV-induced cancers worldwide. The findings emphasize that eliminating cervical cancer and other HPV-related diseases is not only a scientific goal but also a moral imperative requiring global collaboration and local action. Full article
(This article belongs to the Special Issue Viral Infections and Cancer: Recent Advances and Future Perspectives)
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16 pages, 555 KiB  
Article
Surgery for T1/2N0 Oropharyngeal Carcinoma Is a Better Treatment Option than Radiotherapy—A Long-Term Follow-Up Study from a Single Japanese High-Volume Cancer Center
by Masahiro Rokugo, Takeshi Shinozaki, Ryo Ishii, Yusuke Ito, Shingo Sakashita, Genichiro Ishii, Takenori Ogawa, Yukio Katori, Kazuto Matsuura and Ryuichi Hayashi
Cancers 2025, 17(11), 1862; https://doi.org/10.3390/cancers17111862 - 31 May 2025
Cited by 1 | Viewed by 568
Abstract
Background: The proportion of oropharyngeal cancers, especially those that are HPV-associated, is increasing, and both surgery and RT are considered effective initial treatments for early-stage oropharyngeal cancer, regardless of p16 status. However, there are still many unknowns regarding the long-term prognosis after initial [...] Read more.
Background: The proportion of oropharyngeal cancers, especially those that are HPV-associated, is increasing, and both surgery and RT are considered effective initial treatments for early-stage oropharyngeal cancer, regardless of p16 status. However, there are still many unknowns regarding the long-term prognosis after initial treatment, the incidence rate of multiple cancers, and the relationship with p16 status. Methods: We retrospectively analyzed 94 cases of T1/2N0 oropharyngeal squamous cell carcinomas (OPSCCs) treated with surgery or radiotherapy between January 2000 and December 2012 at the Japan National Cancer Center Hospital East. The study items include long-term prognosis, p16 status, and the proportion of patients with multiple cancers after receiving treatment for oropharyngeal cancer. Results: The patients included 80 men and 14 women, whose median age was 68 (35–92). The median follow-up time was 2131 days. T1N0 cancer was observed in 34 patients and T2N0 in 60 patients. Surgery was performed for 74 patients, and radiotherapy for 20 patients. Of the patients who underwent surgery, 57 underwent transoral surgery, and 17 underwent pharyngectomy via transcervical approach. Nine of the 17 patients underwent partial pharyngectomy with free-flap reconstruction. The 5-year overall survival rates were 74.9 and 51.0% (p = 0.035); the 5-year disease-specific survival rates were 86.0 and 64.5% (p = 0.116); and the 5-year local control rates, 76.5 and 59.1% (p = 0.106) for the surgery and radiotherapy groups, respectively. Furthermore, 54 (57.4%) of the 94 cases suffered from multiple primary cancers, of which 29 (30.9%) were in the head and neck region and all were metachronous. Conclusions: Initial surgery for T1/2N0 OPSCCs is a proper therapeutic strategy considering the better overall survival and high incidence of multiple primary cancers. Full article
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12 pages, 965 KiB  
Article
Oropharyngeal and Oral Cancer in Lung Cancer Patients: Do They Present a Worse Prognosis than Isolated Lung Cancer Patients?
by Farzin Falahat Noushzady, Sonia Herrero Álvarez, Joaquín Calatayud Gastardi, Elena María Vara-Ameigeiras, Carlota Mazo Amorós, Irene Serrano-García, Florentino Hernando Trancho, José Ramón Jarabo Sarceda and Ana Maria Gómez Martínez
Cancers 2025, 17(11), 1850; https://doi.org/10.3390/cancers17111850 - 31 May 2025
Viewed by 481
Abstract
Background/objectives: Second primary lung cancer frequently manifests in individuals who have survived head and neck cancer, with this occurrence often being attributed to shared risk factors. The objective of the present study is to compare the prognosis, in terms of survival rate, of [...] Read more.
Background/objectives: Second primary lung cancer frequently manifests in individuals who have survived head and neck cancer, with this occurrence often being attributed to shared risk factors. The objective of the present study is to compare the prognosis, in terms of survival rate, of patients who presented isolated bronchogenic carcinoma (BC) with that of patients who presented with a personal history of BC and associated oropharyngeal and oral cancer (OAOC). Methods: A retrospective longitudinal study was conducted, including all consecutive patients who underwent surgical resection with curative intent for BC in Hospital Clínico San Carlos (HCSC), Madrid, Spain, between December 1989 and December 2024. The survival rate was calculated and compared in two groups of patients: Group 1: 1594 patients with isolated BC and Group 2: 97 patients with BC and OAOC. Results: Group 2 did not show a significant difference in their 60-month survival rate in comparison to Group 1 (HR = 1.23, CI 95% 0.9–1.6) p = 0.14. But when comparing the 120-month survival rate, Group 1 showed a significantly higher survival rate (36.4%, CI 95% 33.9–39%) compared to Group 2, (25.54%, CI 95% 17.78–36.7%) HR= 1.28 (CI 95% 1–1.6), p = 0.04. Disease-free survival showed a non-significant trend of greater severity among patients with a previous history of OAOC. Conclusions: Lung cancer patients who presented with OAOC had worse overall survival compared to patients who presented with isolated lung cancer, and a significant difference was observed at 120 months of follow-up. Full article
(This article belongs to the Section Cancer Survivorship and Quality of Life)
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8 pages, 1153 KiB  
Case Report
Brachial Plexopathy in Head and Neck Cancer Potentially Related to LET-Dependent RBE
by Abanob Hanna, Anthony Casper, Roi Dagan, Hardev S. Grewal, Jiyeon Park, Eric D. Brooks, Erik Traneus, Lars Glimelius, Perry B. Johnson, Mohammad Saki, Yawei Zhang, Twyla R. Willoughby, Julie A. Bradley, Jackson Browne and Mark E. Artz
Biophysica 2025, 5(2), 20; https://doi.org/10.3390/biophysica5020020 - 29 May 2025
Viewed by 539
Abstract
Proton beam therapy for head and neck cancers traditionally employs a fixed relative biological effectiveness (RBE) of 1.1, which may underestimate actual biological effects in critical structures. This study evaluates how Linear Energy Transfer (LET) optimization could potentially prevent radiation-induced brachial plexopathy (RIBP). [...] Read more.
Proton beam therapy for head and neck cancers traditionally employs a fixed relative biological effectiveness (RBE) of 1.1, which may underestimate actual biological effects in critical structures. This study evaluates how Linear Energy Transfer (LET) optimization could potentially prevent radiation-induced brachial plexopathy (RIBP). (1) Case presentation: A 65-year-old male with stage IVA p16-positive oropharyngeal squamous cell carcinoma received pencil-beam-scanning intensity-modulated proton therapy with concurrent cisplatin. Due to a right level 4 neck node, the high-risk target volume overlapped with the brachial plexus, resulting in a D0.1cc of 70.3 Gy (RBE = 1.1). Four years post-treatment, the patient developed progressive right upper extremity paresthesia, weakness, and dysesthesia. Electromyography revealed myokymia consistent with brachial plexopathy, while MRI showed hyperintensity of the right brachial plexus corresponding to the radiation field. Conservative treatment with pentoxifylline, gabapentin, and physical therapy improved his symptoms. (2) Methods: The original treatment plan was retrospectively analyzed using Monte Carlo dose algorithms and LET-dependent RBE models from McMahon and McNamara. An LET-optimized plan was created to limit LETd to 2.0 keV/µm in the brachial plexus. (3) Results: The relative biological equivalent (RBE) dose to 0.1cc of the brachial plexus was 77.8 Gy (CGE RBE), exceeding tolerance. The LET-optimized plan reduced the brachial plexus D0.1cc to 59.4 Gy (RBE = 1.1) and 63.2 Gy (CGE RBE), an 18.8% decrease, while maintaining target coverage. LETd, within the brachial plexus enhancement, decreased from 5.3 to 2.6 keV/μm. (4) Conclusion: This case highlights the potential clinical importance of LET optimization in proton therapy planning, particularly when organs-at-risk overlap with target volumes. By reducing LETd from 5.3 to 2.6 keV/μm and biological equivalent dose by 18.8%, LET optimization could potentially prevent late toxicities, like RIBP, while maintaining target coverage. Full article
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19 pages, 2541 KiB  
Review
Novel Avenues for the Detection of Cancer-Associated Viral Genome Integrations Using Long-Read Sequencing Technologies
by Larissa-Anna Bergmann, Alicja Pacholewska and Michal R. Schweiger
Cancers 2025, 17(11), 1740; https://doi.org/10.3390/cancers17111740 - 22 May 2025
Viewed by 584
Abstract
Human papillomaviruses (HPVs), like many other viruses, are able to integrate their genomes into the host cellular genome. This integration can activate viral oncogenes or alter the function of cellular oncogenes and tumor suppressor genes, thereby increasing the likelihood of HPV-associated tumor development. [...] Read more.
Human papillomaviruses (HPVs), like many other viruses, are able to integrate their genomes into the host cellular genome. This integration can activate viral oncogenes or alter the function of cellular oncogenes and tumor suppressor genes, thereby increasing the likelihood of HPV-associated tumor development. In particular, HPV types 16 and 18 are responsible for over 70% of all cervical, anal, and oropharyngeal cancers worldwide, with rising incidence. Even more, high-resolution mapping of preferred integration sites using LR-Seq technologies offers deep insights into the molecular mechanisms of HPV integration. LR-Seq enables the detection of complex integration patterns, where the viral genome can be replicated and amplified into virus–host concatemers, including events within large structural variations or highly repetitive genomic regions. Furthermore, aligning LR-Seq data to the latest T2T reference genome (hs1) is necessary to provide new information about viral integration in genomic regions that were previously inaccessible, such as centromeres and other structurally complex repeat-rich loci. In this review, we provide insights into HPV genomic integration revealed by LR-Seq technologies, with a particular focus on how the use of the complete T2T reference genome enhances the detection of integration events in previously uncharacterized, repeat-rich regions of the human genome. Full article
(This article belongs to the Special Issue Long-Read Sequencing in Cancer)
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21 pages, 312 KiB  
Review
Update: Immunotherapeutic Strategies in HPV-Associated Head and Neck Squamous Cell Carcinoma
by Fangdi Sun and A. Dimitrios Colevas
Viruses 2025, 17(5), 712; https://doi.org/10.3390/v17050712 - 16 May 2025
Viewed by 970
Abstract
The incidence of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) has increased substantially over the past three decades, and since 2017, it has been recognized in the AJCC staging system as distinct from its HPV-negative counterpart. The underlying mechanisms of HPV-associated carcinogenesis, [...] Read more.
The incidence of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) has increased substantially over the past three decades, and since 2017, it has been recognized in the AJCC staging system as distinct from its HPV-negative counterpart. The underlying mechanisms of HPV-associated carcinogenesis, tumor microenvironment, and host immune response represent opportunities for therapeutic development. While anti-PD-1 immunotherapy is now part of standard treatment for recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) in general, there are no established immunotherapeutic strategies specifically for HPV-related HNSCC. In this context, multiple emerging approaches are being actively studied—among these are therapeutic vaccines with or without anti-PD-(L)1 adjuvants, peptide–HLA-based immunotherapeutic platforms, and adoptive cell therapies including tumor-infiltrating lymphocytes (TILs), T-cell receptor (TCR) therapy, and chimeric antigen receptor (CAR) T-cell therapy. Beyond further maturation of these novel immunotherapeutic strategies, additional work is needed to delineate the optimal disease state of application (localized versus recurrent/metastatic), as well as in the development of small molecule inhibitors targeting HPV-specific mechanisms of viral oncogenesis. Full article
(This article belongs to the Special Issue Advancements in Immunotherapy for Human Papillomavirus)
13 pages, 16048 KiB  
Article
Characterization of the Antiproliferative and Antimetastatic Properties of Centrapalus pauciflorus Meroterpenoid Centrapalus Coumarin F
by Hazhmat Ali, Shelan Rasool, Muhammad Bello Saidu, Péter Germán, Gábor J. Szebeni, Enikő Szabó, Dóra Rédei, Judit Hohmann and István Zupkó
Int. J. Mol. Sci. 2025, 26(10), 4489; https://doi.org/10.3390/ijms26104489 - 8 May 2025
Viewed by 807
Abstract
The current study examined the in vitro antineoplastic potentials of centrapalus coumarin F (CCF) obtained from aerial parts of Centrapalus pauciflorus (Willd.) H.Rob. (Asteraceae). Cytotoxic activity was tested against a panel of human adherent cancer cell lines, including breast, cervical, and oropharyngeal cancer [...] Read more.
The current study examined the in vitro antineoplastic potentials of centrapalus coumarin F (CCF) obtained from aerial parts of Centrapalus pauciflorus (Willd.) H.Rob. (Asteraceae). Cytotoxic activity was tested against a panel of human adherent cancer cell lines, including breast, cervical, and oropharyngeal cancer and glioblastoma. Cell cycle analyses using flow cytometry and Hoechst 33258-propidium iodide (HOPI) fluorescent double staining were used to describe the proapoptotic property of CCF. Wound healing assessment and the Boyden chamber assay were performed to characterize the antimetastatic action of the compound. The firefly luciferase assay was applied to clarify the action of CCF on estrogenic receptors. CCF demonstrated remarkable selective growth inhibition against the HPV-18-positive human cervical cancer cell line HeLa (IC50 = 2.28 µM). The compound elicited crucial markers of apoptosis, inhibited the migration and invasion capacity of HeLa cells, and demonstrated an antiestrogenic property. Our current data indicate that the meroterpenoid scaffold presented here displays remarkable antiproliferative and antimetastatic effects on HeLa cells and can be considered a valuable model for designing further analogs targeting cervical carcinoma. Full article
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4 pages, 812 KiB  
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Immune Checkpoint Inhibitor-Related Sjögren’s Syndrome: An Ocular Immune-Related Adverse Event
by Hideki Fukuoka, Akifumi Matsumoto and Chie Sotozono
Diagnostics 2025, 15(9), 1168; https://doi.org/10.3390/diagnostics15091168 - 4 May 2025
Cited by 1 | Viewed by 683
Abstract
A 67-year-old male with metastatic human papillomavirus (HPV)-positive oropharyngeal cancer receiving pembrolizumab (anti-programmed cell death protein 1 [PD-1] immune checkpoint inhibitor) presented with bilateral ocular dryness. It is important to note that these symptoms appeared eight months after the initiation of the pembrolizumab [...] Read more.
A 67-year-old male with metastatic human papillomavirus (HPV)-positive oropharyngeal cancer receiving pembrolizumab (anti-programmed cell death protein 1 [PD-1] immune checkpoint inhibitor) presented with bilateral ocular dryness. It is important to note that these symptoms appeared eight months after the initiation of the pembrolizumab therapy. Ophthalmologic evaluation revealed keratoconjunctivitis sicca with characteristic bulbar fluorescein staining and the Schirmer test showed 0 mm bilaterally. Serological testing demonstrated positive antinuclear and anti-SSb/La antibodies, consistent with Sjögren’s syndrome as an immune-related adverse event (irAE). Treatment with topical fluorometholone 0.1% and diquafosol 3% led to complete symptom resolution within one year while maintaining cancer immunotherapy. Long-term follow-up over 3.5 years demonstrated sustained ocular improvement and a favorable oncologic response without development of systemic autoimmune manifestations. This case highlights that Sjögren’s syndrome as an irAE may present with isolated ocular manifestations, which could be overlooked in clinical practice. Full article
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Article
Mechanisms of Viral DNA Replication of Human Papillomavirus: E2 Protein-Dependent Recruitment of E1 DNA Helicase to the Origin of DNA Replication
by Anshul Rana, Gulden Yilmaz, Esther E. Biswas-Fiss and Subhasis Biswas
Int. J. Mol. Sci. 2025, 26(9), 4333; https://doi.org/10.3390/ijms26094333 - 2 May 2025
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Abstract
Human papillomaviruses (HPVs) are small double-stranded DNA viruses that infect epithelial cells and cause cervical, anogenital, and oropharyngeal cancers. HPV genome replication relies on the viral E1 and E2 proteins to initiate DNA replication. The first step is the assembly of the E1-E2 [...] Read more.
Human papillomaviruses (HPVs) are small double-stranded DNA viruses that infect epithelial cells and cause cervical, anogenital, and oropharyngeal cancers. HPV genome replication relies on the viral E1 and E2 proteins to initiate DNA replication. The first step is the assembly of the E1-E2 complex at the origin of replication. We have examined the role of full-length HPV E1 helicase and its interaction with E2 in pre-initiation complex formation. Electrophoretic mobility shift assays (EMSAs) with purified E1 and E2 proteins revealed that the HPV genome does not have a specific E1 binding site, or such a sequence is not required for pre-initiation complex formation. E1 alone did not show any binding to the origin DNA sequences, while E2 facilitated E1 recruitment to the origin, forming the E1-E2-DNA ternary complex. Formation of such a complex required at least two E2 binding sites. These findings led us to propose a novel mechanism in which E2 dimers serve as the primary recruiters of E1 to form the pre-initiation complex. This study provides new insights into the mechanistic role of E2 in the recruitment of E1 at the origin of HPV DNA replication, enhancing our understanding of HPV biology and potentially informing future therapeutic strategies. Full article
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