Search Results (361)

Background: Human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) generally has a more favorable prognosis compared to HPV-negative cases. Overexpression of p16^INK4a is widely used as a surrogate marker for HPV-induced carcinogenesis, and it also represents an important tumor suppressor gene, the second most frequently altered after TP53. In turn, mutations in TP53 are characteristic of tumors linked to smoking and alcohol consumption and p53 expression is consistently associated with worse clinical outcomes. Aims: Investigate the impact of p53 immunohistochemical expression on prognosis of OPSCC. Methods: This retrospective study included 155 OPSCC patients with longitudinal follow-up exceeding 10 years. Immunohistochemistry was used to evaluate p53 protein expression. Clinicopathological associations were performed to evaluate the prognostic impact of p53 protein expression in OPSCC HPV-positive and HPV-negative tumors. Results: Among the 155 OPSCC cases, 90 (58.1%) were classified as HPV-positive and 65 (41.9%) as HPV-negative. HPV status was inversely associated with p53 positivity, with HPV-negative tumors showing a higher frequency of p53 expression (p < 0.0001). Patients with HPV-positive tumors experienced better clinical outcomes than those with HPV-negative disease, including cancer-specific survival (CSS; HR: 3.47, 95% CI 1.16–10.4, p = 0.02) and disease-free survival (DFS; HR: 3.73, 95% CI 1.29–10.7, p = 0.01), whereas p53 positivity alone was not independently associated with survival. Notably, individuals with HPV-negative and p53-positive tumors exhibited the poorest outcomes, in contrast to patients with HPV-positive OPSCC, regardless of p53 expression. Conclusions: Patients with HPV-negative and p53-positive OPSCC showed inferior clinical outcomes compared with their HPV-positive counterparts, independent of p53 status. These findings underscore the prognostic relevance of jointly evaluating HPV status and p53 expression in OPSCC and support more refined risk stratification and personalized therapeutic strategies. Full article

Background and Objectives: Recent evidence demonstrates additional survival benefit of immune checkpoint inhibitor (ICI) therapy in the treatment of head and neck squamous cell carcinoma (HNSCSC) and nasopharyngeal carcinoma (NPC). However, overall outcomes remain relatively stagnant despite this significant progress. Therapeutic vaccines are a promising adjunct to existing systemic therapy strategies in HNSCC and NPC. This review aims to summarize current evidence, review ongoing studies, and discuss areas of opportunity and potential future directions of vaccine therapy in this space. Methodology: A comprehensive review of the current literature was conducted through database searches on PubMed and ClinicalTrials.gov. Studies were stratified by tumor type, vaccine delivery platform, and early versus recurrent metastatic (RM) disease. Results: Therapeutic vaccines in combination with ICI for HPV-associated HNSCC have shown the most promise, though modest. Vaccine delivery in HPV-negative HNSCC and NPC are still in early development. Integration of therapeutic vaccines across these tumor types is challenged by immune escape mechanisms, lack of viable targets, and tumor heterogeneity. Conclusions: Early data suggest that therapeutic vaccines in combination with ICIs may offer additional benefit in the treatment of HNSCC and NPC, especially in RM HPV-associated HNSCC. Future efforts should validate these early findings through phase 3 trials. Data regarding therapeutic vaccines combined with chemotherapy or radiation is limited but may also provide additional benefit. Full article

Background/Objectives: Long-term exposure to high-risk human papilloma virus (HPV) leads to high-grade squamous intraepithelial lesions (HSILs), which may develop into cancer. Various proteins and metabolites change during the development of cervical cancer; thus, assessing the dysregulated molecules and pathways in HSILs is important to elucidate early pathological mechanisms and identify potential intervention targets. Methods: In this study, we performed proteomic and metabolomic analyses in five pairs of HPV-positive HSIL tissues and paired normal tissues. Immunohistochemistry (IHC) was applied to validate the levels of carnitine palmitoyltransferase 1A (CPT1A) in HSIL tissues. Quantitative real-time PCR and Western blot were used to detect the expression levels of CPT1A in cervical cancer cell lines. Results: In proteomic analysis, 836 proteins showed significant changes. Functional analyses of the differentially expressed proteins indicated that metabolic pathways, oxidative phosphorylation and ribosome are the top three enriched pathways. In metabolomic analysis, 105 metabolites were differentially altered. Most metabolites were involved in lipid metabolism, such as phosphatidylethanolamine (PE), phosphatidylinositol (PI) and L-palmitoylcarnitine. Integrated proteomics and metabolomics revealed that the metabolic pathway was the most enriched pathway that contained the maximum number of differentially expressed metabolites and proteins. In vitro, we found CPT1A was upregulated in HSIL tissues and in cervical cancer cell lines. Conclusions: Our findings characterize the protein and metabolite alterations in HSILs, which may represent molecular features associated with disease progression. Full article

Background/Objectives: Human papillomavirus (HPV) is the most common sexually transmitted infection worldwide and causes cervical cancer in women. Patients with human immunodeficiency virus (HIV) are particularly susceptible to this virus. An effective vaccine against high-risk HPV genotypes is available. This study sought to evaluate barriers to HPV vaccination in HIV-positive female patients between the ages of 18 and 65 in a county clinic in Houston. Methods: A cross-sectional survey was conducted in May–June 2025 with 131 patients at Thomas Street Health Center in Houston. The survey assessed patient demographics, attitudes toward and knowledge of HPV vaccination (at least one dose), as well as self-reported cervical dysplasia and HPV infection history. Clinical data on available cervical dysplasia history were also gathered from the electronic medical record. Descriptive statistics were compiled, and comparisons between vaccinated and unvaccinated participants were performed using one-way analysis of variance for continuous variables and chi-square tests for categorical variables in R. Results: 75% of patients had prior knowledge of the HPV vaccine, but only 33% reported receiving at least one dose. The most common reason for not receiving the vaccine was never having been offered the vaccine by a provider. Separately, almost 40% of unvaccinated individuals had never heard of the vaccine. Of note, only 8.6% of respondents reported fully understanding the implications of vaccination and still choosing to decline. In this cross-sectional study, there was no statistically significant association between vaccination status and either recent dysplasia history in the electronic record or reported dysplasia or HPV infection history. Among eligible unvaccinated participants, 41% received the HPV vaccine after completing the survey. Conclusions: Addressing gaps in HPV vaccine communication and supporting clinicians in delivering confident counseling may improve vaccination rates in this at-risk population. Full article

Background: Human papillomavirus (HPV) vaccination is a major concern and highly effective strategy for preventing cervical cancer and other related diseases. Despite the inclusion of the HPV vaccine in the Saudi national immunization program and recent school-based initiatives, vaccine uptake remains suboptimal, mainly due to the hesitancy of parents. Evidence regarding HPV vaccine hesitancy in the Aseer region of Saudi Arabia is limited. Objectives: This study aimed to assess the level of the HPV vaccine hesitancy, knowledge, attitude and barriers among parents in the Aseer region of Saudi Arabia using the World Health Organization (WHO) HPV Vaccine Hesitancy Scale (VAS). Methods: A cross-sectional study was conducted among parents residing in the Aseer region, Saudi Arabia. Data were collected using a structured questionnaire that included sociodemographic characteristics, knowledge, barriers and the validated nine-item WHO HPV Vaccine Hesitancy Scale. Data was expressed in numbers (%) for categorical variables and mean ± SD for continuous variables. Independent t-tests and one-way ANOVA were used for inferential statistics. Results: A total of 379 parents participated in the study. Overall, 49% of parents exhibited high HPV vaccine hesitancy. The most frequently reported barriers were safety concerns (82.6%), insufficient information (80.3%) and fear of side effects (79.4). Lower hesitancy scores were observed among parents aged ≥ 46 years than among those aged 18–25 years (p = 0.022), and respondents with postgraduate education were less hesitant than those with a high school education or less (p = 0.030). Parents whose children were fully vaccinated exhibited significantly lower hesitancy scores compared with those whose children were unvaccinated (p = 0.004). Conclusions: The HPV vaccine hesitancy among parents in the Aseer region is greatly influenced by the age of the parents, their educational level, and the child’s vaccination history. Higher hesitancy among younger parents, those with lower educational levels, and parents of unvaccinated children highlights priority groups for targeted interventions. Strengthening healthcare-provider recommendations and implementing culturally tailored, evidence-based communication strategies may improve HPV vaccine acceptance and support national cervical cancer prevention efforts in Saudi Arabia. Full article

The COVID-19 pandemic has significantly impacted public health in Mexico. Background/Objectives: This study evaluated its impact on the frequency of vaccine-preventable diseases (VPDs) from 2020 to 2024. Methods: The analyzed information was extracted from the weekly epidemiological bulletins, which compile the suspected, probable, and confirmed cases reported to the Ministry of Health. The epidemiological behavior of VPDs was analyzed with endemic channels based on 2014–2019 data. An endemic channel is a graphical tool that is used to plot a central tendency and its limits; with this tool we can detect the presence of an epidemic and quantify it. Between 2020 and 2024, VPDs presented variable patterns due to the pandemic. Results: Rotavirus cases exhibited an 81% negative deviation in 2020 and a final 47% negative deviation in comparison with the expected values from 2014–2019. Chickenpox declined by 91% in 2020, with a partial recovery in reports afterward. Hepatitis A and B declined initially, but hepatitis B surpassed pre-pandemic levels later. Mumps declined by 45% in 2020, with a partial recovery, remaining 35% below expected reports. Meningeal and pulmonary tuberculosis increased by 125% and 33%, respectively. Human Papilloma Virus (HPV) infection and mild cervical dysplasia showed negative deviations, with partial increases later. However, severe dysplasia and in situ cervical cancer reports exceeded expected levels. Conclusions: Overall, several VPDs showed negative deviations, which could increase the size of the susceptible population. In contrast, increases in tuberculosis and HPV infection present a major challenge for health systems, given their chronic and high treatment costs. Full article

In this work, we evaluate the efficiency of a DNA purification protocol from gynecological samples using locally synthesized Fe₃O₄@SiO₂ magnetic microparticles and a low-cost, guanidinium thiocyanate (GITC)-free lysis buffer. The microparticles were characterized by SEM, EDS, FTIR, and magnetic measurements, confirming the formation of compact silica-coated aggregates with suitable magnetic responsiveness for rapid and complete capture. Using this material in combination with a simple, GITC-free lysis buffer, we achieved DNA extraction yields comparable to those obtained with standard methods based on chaotropic salts. The purified DNA showed high compatibility with molecular assays for the detection of Chlamydia trachomatis, Ureaplasma urealyticum, Mycoplasma hominis, and human papilloma virus. Clinical validation demonstrated excellent diagnostic performance, with only a few discrepancies observed in samples near the detection threshold of qPCR, a limitation shared with commercial kits. Overall, the method represents a low-cost, safe, and sustainable alternative for routine clinical and epidemiological applications, compared to methods based on chaotropic salt buffers. Furthermore, it reduces reliance on imported commercial consumables and minimizes the handling of hazardous reagents. Full article

Recognizing cervical cancer as a major public health concern, Romania was among the first EU countries to introduce human papilloma virus (HPV) vaccination in 2008. Despite multiple strategies implemented over the past 17 years, HPV vaccine coverage remains one of the lowest in the EU, while cervical cancer mortality rates are among the highest. To explore the underlying factors, we conducted a cross-sectional study involving 209 family physicians at the national level. The study assessed their attitudes, practice, knowledge, and training needs related to HPV vaccination. The majority of physicians (90%) reported that they provide HPV vaccination services, and 88.5% considered themselves to have good and very good knowledge about HPV, which they routinely share during consultations with patients. However, respondents noted that both physician and public attitudes toward HPV vaccination are only moderately positive, which limits vaccine uptake and the success of prevention efforts. Parental hesitation was the main barrier, mentioned by 81.8% of respondents. The majority (71.3%) of doctors indicated that they were able to adequately respond to patients’ questions, but 81.4% of respondents expressed the view that additional training is needed for healthcare professionals on HPV infection and vaccination. These findings highlight the need for coordinated efforts to increase demand and trust in HPV vaccination. Recommended strategies include targeted professional training, public information campaigns, and the development of strong cross-sector partnerships to support vaccination efforts. Full article

Evidence on the contribution of human papillomaviruses (HPVs) to the development of esophageal papillomas is still controversial. Esophageal papillomatosis (EP) is considered an exceedingly rare, but distinct entity within esophageal proliferations, with about 57 cases published so far. Tissues derived from an EP case and from non-EP esophageal papillomas were investigated for the presence of HPVs and virus-positive specimens were subsequently analyzed for transcriptional activity and surrogate markers of infection. Low-risk type HPV6 DNA was detected in a subset of the esophageal papillomatous tissues, including EP, and a variant isolate belonging to lineage A. In the EP tissue, the abundant expression of the viral E6/E7 mRNA and the presence of HPV6-specific E1^E4 transcripts, the latter indicative of productive viral infection, were detected. An analysis of HPV-specific neutralizing antibodies in sera obtained from the EP case during natural infection as well as after HPV vaccination revealed that, despite extensive manifestation, HPV6-specific antibodies were absent during natural infection and only elicited after repeated HPV immunizations. Although limited by a small sample size, this exploratory study suggests a possible involvement of HPV6 in the development of EP. Furthermore, this study may contribute to the evidence distinguishing EP from less extensive forms of non-EP esophageal squamous papillomas. Full article

Cervical cancer, primarily caused by high-risk Human Papilloma Virus (HPV), remains a global health concern. Prognostic biomarkers reflecting systemic inflammation and immune response—the Systemic Immune-Inflammation Index (SII) and the Systemic Inflammation Response Index (SIRI)—have recently attracted interest for their potential predictive value in cervical cancer. We conducted a retrospective observational study including 344 patients who underwent loop electrosurgical excision of cervical intraepithelial neoplasia at Semmelweis University, Budapest, Hungary, between 2021 and 2024. Demographic, cytologic, histologic, and laboratory data were collected, and SII and SIRI were calculated. Statistical analyses, including Receiver Operating Characteristic (ROC) analyses, were performed. Higher SII and SIRI values were significantly associated with higher-grade lesions and invasive carcinoma. ROC analyses indicated good discriminatory performance, with negative predictive values of 96–100%, suggesting potential utility in ruling out malignant transformation. SII and SIRI are simple, cost-effective, and minimally invasive biomarkers that correlate with lesion severity in cervical disease. Their high negative predictive value supports a potential role as complementary rule-out tools in diagnostic evaluation. Further prospective studies are needed to validate these findings and to define clinically meaningful cut-off values for routine use. Full article

Head and neck cancer (HNC) affects nearly 1 million people every year. The main risk factors include tobacco, alcohol, or human papilloma virus (HPV) viral infections, which contribute to HNC development through various, mostly unknown, mechanisms. One of these postulated mechanisms is cellular senescence. This biological aging-associated process is responsible not only for the arrest of cellular growth and division but also mediates the modulation of cell metabolism and secretory phenotype. Consequently, it may play a crucial role in carcinogenesis, which makes it an interesting topic in the context of cancer development, prognosis, prevention, and therapy. This review focuses on the current state of knowledge regarding all aspects of the association between cellular senescence and head and neck cancer. Full article

Introduction: Histopathologic assessment of surgical specimens imparts crucial information that is essential for diagnosis, treatment planning and prognostication for patients with Oropharyngeal Squamous Cell Carcinoma (OPSCC). This review explores the range of diagnostic techniques utilized to assess the HPV (Human Papilloma Virus) status in OPSCC. It covers both traditional methods—such as p16 immunohistochemistry, HPV in situ hybridization, and DNA polymerase chain reaction (PCR)—and newer, evolving strategies including circulating HPV tumor DNA analysis and oral HPV DNA/mRNA PCR testing. Discussion: There are currently several histopathologic techniques for the diagnosis of HPV-associated OPSCC. This complexity of care has led to guidelines from numerous authorities (NCCN, ASCO, CAP), which this paper discusses and summarizes for head and neck oncology specialists. Conclusion: The ability to detect HPV in HPV-associated OPSCC is imperative for diagnosis, prognostication, staging, and management of the disease. Advances including liquid biopsy (TTMV-HPV DNA) may be utilized as an adjunct to diagnosis, treatment, and cancer surveillance in the future. Full article

Background/Objective: Cervical cancer incidence is rising in Puerto Rico (PR) despite being preventable through HPV vaccination, Pap smear screening, and the timely treatment of dysplasia. This study evaluated the presence of single-nucleotide polymorphisms (SNPs) in Toll-like receptors (TLR4 and TLR9) among women with cervical dysplasia and HPV infection, as potential immune-related susceptibility factors. Methods: Cervicovaginal samples from 210 Hispanic women in PR were analyzed for dysplasia severity and HPV genotype. Demographic data were collected. Seven SNPs (four in TLR4, three in TLR9) were examined using PCR-RFLP and AS-PCR. Associations between SNP frequency, dysplasia severity, and high-risk HPV (HR-HPV) were assessed. Results: HR-HPV was found in 64% of severe dysplasia cases versus 46% of mild/negative cases (p < 0.025). The TLR4 AG (rs4986790) and CT (rs1927911) genotypes were more frequent in severe dysplasia. For TLR9, CT heterozygotes (rs187084) and the TC genotype (rs5743836) were also enriched in severe dysplasia. Conclusions: This first PR-based study shows that TLR4 and TLR9 SNPs significantly correlate with HR-HPV infection and dysplasia severity, supporting further research on their potential as biomarkers for cervical cancer prevention. Full article

Background/Objective: High-risk human papillomavirus (hrHPV) is an established causative agent for the malignant transformation of cervical cells that can be detected using the Papanicolaou (Pap) smear test. A call by the World Health Organization (WHO) for global collective efforts towards eliminating cervical cancer has endorsed hrHPV DNA testing as an alternative screening test. The objective of this study was to determine the diagnostic utility of hrHPV DNA testing in detecting high-grade cervical intraepithelial lesions (HSILs) in unvaccinated women with abnormal Pap smears and histopathologically confirmed CIN3 and carcinoma. Methods: This study included 111 cervical tissues with a histopathological confirmation of the cervical intraepithelial neoplasia grade (CIN3) and malignancy. Tissues were sectioned, dewaxed, and digested, and DNA was extracted and tested for hrHPV using the Abbott RealTime HR HPV assay. Pap smear results associated with the tissue samples were extracted from corresponding clinical records, and data was analyzed using R-statistical software. Results: Extracted Pap smear records for the 111 cervical tissue samples indicated that 89 (80.2%) had a high-grade intraepithelial lesion (Pap-HSIL), 20 (18%) had squamous cell carcinoma (Pap-SCC), and two (1.8%) had Pap-adenocarcinoma. A total of 68/89 (76.4%) of Pap-HSIL, 15/20 (75%) of Pap-SCC, and ½ (50%) of Pap-adenocarcinoma cases had detectable hrHPV DNA. Conclusions: This study’s findings demonstrate that the Pap smear is still a valuable screening test especially for detecting both hrHPV-dependent and -independent cervical dysplasia in unvaccinated populations. While considerations are made to improve cervical cancer screening, including the introduction of hrHPV DNA testing in national cervical cancer screening programs, there is a need for the careful interpretation of molecular testing results for clinical intervention. This is especially important for hrHPV-independent cervical dysplasia screening, since this can have dire implications for clinically asymptomatic women. Full article

Nasopharyngeal carcinoma (NPC) is a malignant tumor in which the etiologic contribution of Epstein–Barr virus (EBV) is well established. However, similar to that of oropharyngeal carcinoma, some papers reported that human papilloma virus (HPV) contributed to the development of NPC in non-endemic regions. Previously, we conducted a study on HPV infection in patients with NPC between 1996 and 2015 in our department. The current study aims to evaluate the incidence and role of HPV infection in NPC pathogenesis using samples of NPC after 2015. Paraffin-embedded tumor samples from 26 patients with NPC who were treated at our department between 2015 and 2022 were analyzed. HPV polymerase chain reaction, p16 immunohistochemistry, HPV genotyping, and in situ hybridization for EBV-encoded RNA were performed to determine the viral infection status. Of the 26 patients, 19 (73%) were EBV-positive and HPV-negative, 1 (4%) was EBV-negative and HPV-positive, and 6 (23%) were negative for both EBV and HPV. The detection rate of HPV has slightly increased from 3% to 4% over the past decade. Although Japan is a non-endemic region for NPC, HPV infection is exceedingly rare and may have a limited role in NPC development in Japan. However, the detection rate of HPV has not significantly changed in the past decade, further supporting the view that HPV has a relatively small impact on the pathogenesis of NPC in Japan. Full article