We evaluated incidence of oral HPV infection, which precedes HPV-related oropharynx cancer.

In this prospective multicenter cohort of participants with HIV and demographically similar participants without HIV, oral rinse and gargle samples were collected every 6-12 months and tested for 35 HPV types (anyHPV), 13 of which were oncogenic (oncHPV). Kaplan Meier and Cox regression were used for incidence curves and clustered risk factor hazard ratios. Logistic regression was used to determine relative odds of same infection at next visit.

The 1587 participants had a median follow-up of 3.67 years, 422 had 708 incident type-specific oral HPV detected. The most common oncHPV was HPV16 [incidence rate = 7.8 per 1000 person-years (95 %CI 5.8-10.6)]. At 5 years, the cumulative incidence of anyHPV, oncHPV and HPV16 was 34.9 % (95 %CI = 31.9 %, 38.3 %), 17.1% (95 %CI = 14.8 %, 19.8 %) and 4.0 % (95 %CI = 2.9, 5.6 %), respectively. Risk of incident oral HPV infection was independently associated with a higher number of oral sex partners, current smoking, younger age, prevalent oral anyHPV, living with HIV and lower CD4 counts. Prevalent oncHPV at baseline had greater odds of being re-detected at subsequent visits than an incident oncHPV detected for the first-time at a later visit. Detection of oral HPV type at one visit was associated with highly elevated odds of detecting that same type-specific infection at the next visit (OR > 100).

Cumulative incidence of oral HPV is increased among PLWH and with prevalent oral HPV, represents a mix of new and intermittently detected infections, and is higher among those with repeated detection of oral HPV.

Oropharyngeal cancer is the eighth most common cancer among US men and its incidence is sharply rising. Oropharyngeal cancer manifests in two major ways: the classic form is prevalent among people who use alcohol and tobacco heavily, while a growing subset of incident cases is associated with human papillomavirus-16 (HPV) and transmitted via oral sex. Gay and bisexual men appear at higher risk for each etiologic subset of oropharyngeal cancer than heterosexual men. We conducted a cross-sectional study to learn how tobacco use, hazardous drinking, and other key risk factors affect gay and bisexual men's perceptions of oropharyngeal cancer risk and beliefs about screening at a doctor's office and self-screening at home.

We recruited 1,699 gay and bisexual men from two dating websites to participate in an online survey. We asked about tobacco use, alcohol consumption, sexual history, and other risk factors for oropharyngeal cancer. The survey also investigated participants' perceptions of oropharyngeal cancer risk and potential worry related to screening. We analyzed results at the bivariate level and in multivariable regression models. We used logistic regression to analyze categorical data and linear regression to analyze continuous data.

Average age of participants was 41.5 (SD = 12.7) years. Most were cisgender (95%), and identified as gay (80%), while 19% were bisexual or pansexual, with 2% reporting being queer or a self-described sexuality. Factors associated with high perceived oropharyngeal cancer risk perceptions were cigarette smoking, using both cigarettes and vaping, being gay identified, number of sexual partners in the last 12 months, and having poor mouth/teeth condition. Factors associated with oropharyngeal cancer screening worry were being Hispanic, having queer/self-described sexuality, not having health insurance, and having poor mouth/teeth condition. No factors were associated with self-screening at home. Alcohol use was not associated with oropharyngeal cancer risk perception.

This study examines oropharyngeal cancer risk perceptions among gay and bisexual men. Health promotion efforts to reduce oropharyngeal cancer risk among gay and bisexual men should involve comprehensive oral health, sexual health, and tobacco use education. Researchers should continue investigating acceptable and effective home self-screening methods for HPV-associated cancers.

The high prevalence of human papillomavirus (HPV) infection in oropharyngeal squamous cell carcinoma (SCC) is well established, and p16 expression is a strong predictor. HPV-related tumors exhibit unique mechanisms that target p16 and p53 proteins. However, research on HPV prevalence and the combined predictive value of p16 and p53 expression in head and neck cutaneous SCC (HNCSCC), particularly in Asian populations, remains limited. This retrospective study surveyed 62 patients with HNSCC (2011-2020), excluding those with facial warts or other skin cancer.

To explore the prevalence of HPV and the predictive value of p16 and p53 expression in HNCSCC in Asian populations.

All patients underwent wide excision and biopsy. Immunohistochemical staining for HPV, p16, and p53 yielded positive and negative results. The relevance of each marker was investigated by categorizing the tumor locations into high-risk and middle-risk zones based on recurrence frequency.

Of the 62 patients, 20 (32.26%) were male, with an average age of 82.27 years (range 26-103 years). High-risk included 19 cases (30.65%), with the eyelid and lip being the most common sites (five cases, 8.06%). Middle-risk included 43 cases (69.35%), with the cheek being the most common (29 cases, 46.77%). The p16 expression was detected in 24 patients (38.71%), p53 expression in 42 patients (72.58%), and HPV in five patients (8.06%). No significant association was found between p16 expression and the presence of HPV (P > 0.99), with a positive predictive value of 8.33%.

This study revealed that p16, a surrogate HPV marker in oropharyngeal SCC, is not reliable in HNCSCC, providing valuable insights for further research in Asian populations.

To explore the diversity of non-oncogenic papillomaviruses in saliva samples from people living with HIV using nanopore amplicon-based sequencing for detection and typing.

This was a secondary analysis of data from the nanopore sequencing of amplicons obtained from polymerase chain reaction detection of papillomaviruses from 127 samples of people living with HIV. The sequencing data was cleaned and analyzed using a series of bash, Python and R scripts to produce output based on comparisons with the PAVE reference database for all known non-oncogenic papillomaviruses.

A total of 171,194 reads corresponding to 201 known papillomavirus types were obtained from the data. Most of these reads (69%), belonged to the human non-oncogenic papillomavirus types. The most abundant nonhuman and non-oncogenic PV, Trichechus manatus latirostris papillomavirus 4 in 99% of the samples. There were nine other less abundant non-oncogenic papillomaviruses that were found in 95% or more of the samples as mixed infections.

This study demonstrates that there are many non-oncogenic PV infections in samples from PLHIV, most of which are mixed infections from this setting. It is important to note that the non-human non-oncogenic PVs, as a potential one health concern, were highly prevalent in this population.

Artificial intelligence (AI) systems may personalise radiotherapy by assessing complex and multifaceted patient data and predicting tumour and normal tissue responses to radiotherapy. Here we describe three distinct generations of AI systems, namely personalised radiotherapy based on pretreatment data, response-driven radiotherapy and dynamically optimised radiotherapy. Finally, we discuss the main challenges in clinical translation of AI systems for radiotherapy personalisation.

Due to the association with the causal human papillomavirus 16 (HPV16) infection, oropharyngeal squamous cell carcinoma is now separated into two distinct entities depending on HPV16 positivity. More recent data show a diversified picture of the importance and prevalence of the surrogate parameter p16 (discordance) for a definitive HPV16 association, which varies worldwide. In the context of preventive options, vaccination is of major importance and HPV screening of healthy people of less importance. The current CME article excerpts parts of the new German S3 guideline on diagnosis, treatment, prevention, and aftercare of oro- and hypopharyngeal cancer (version 1.0, March 2024; Association of the Scientific Medical Societies in Germany [AWMF] registration number 017-082OL).

Subgroups with a poorer prognosis exist among patients with human papillomavirus positive oropharyngeal squamous cell carcinoma (HPV-positive OPSCC). This study aims to identify histological and genetic differences within HPV-positive OPSCC and correlate these findings with patient outcomes.

The study included 102 OPSCC patients, all tested positive for high-risk HPV DNA and p16INK4a expression. Based on histomorphological classification (HPV Prediction Classification, HPV PC), all cases were categorized as either classic HPV-positive OPSCC (cHPV) or non-classic HPV-positive OPSCC (non-cHPV). Next-generation sequencing (NGS) of selected genes was performed on 55 tumor samples, correlating results with morphological status and survival.

Of all cases, 49 % (n = 50/102) were categorized as non-cHPV, histomorphologically resembling HPV-negative OPSCC, and showed significantly poorer overall survival (p = 0.004) and five-year survival rate (5YS: 83.9 % vs. 58.4 %). Multivariate analyses identified HPV PC as an independent prognostic marker (p = 0.027). NGS revealed loss-of-Function (LOF) mutations in TP53 in three non-cHPV samples. Additionally, PIK3CA/PTEN mutations were found in 35.7 % (10/28) of non-cHPV cases. The cumulative burden of gene mutations was higher in the non-cHPV subgroup compared to the cHPV subgroup (n = 53, p = 0.1).

HPV PC distinguished two histomorphological subgroups within HPV-positive OPSCCs: cHPV with excellent prognosis and non-cHPV with poorer overall survival. Non-cHPV tumors also exhibited higher overall mutation rates, notably LOF-TP53 and PIK3CA/PTEN mutations. These morphological subtypes, along with their corresponding mutational profiles, warrant further investigation as potential biomarkers for de-escalation intervention trials.

Human papillomavirus (HPV) infections in men remain under-researched despite their critical role in disease transmission and the increasing incidence of HPV-related cancers. This study investigates the clinical and molecular characteristics of anogenital HPV infections in men, emphasizing genotype prevalence, diagnostic methods, and lesion variability.

A cross-sectional study was conducted on 70 men aged 18-65 years with clinically diagnosed anogenital HPV infection. Lesions were characterized by morphology and location. HPV DNA was analyzed using INNO-LiPA (INNOvative Line Probe Assay), Hybrid Capture II (HC II), and polymerase chain reaction (PCR) assays to determine genotype distribution. Associations between clinical features and HPV genotypes were assessed using multivariate statistical analyses.

Lesions varied in morphology, with verrucous (52.86%) and papular (30%) types being the most common. Localization patterns showed predominance on the penis radix (34.29%) and shaft (27.14%). Molecular testing revealed HPV DNA in 88.57% of the cases using INNO-LiPA, compared to 45% and 40% with HC II and PCR, respectively. Low-risk (LR) genotypes, particularly HPV6, dominated single infections, comprising 68.57% of the cases, while high-risk (HR) genotypes accounted for 20%. Mixed LR and HR infections were observed in 14.29% of the lesions, with greater diversity noted in distal genital regions. Notably, condyloma plana and lesions on the inner prepuce exhibited a higher prevalence of HR and mixed infections. Age and lesion duration showed trends toward older patients and longer disease duration in cases involving perianal and extragenital condylomas, though these findings were not statistically significant. No direct correlation between lesion type or localization and specific genotypes was identified, underscoring the heterogeneity of HPV clinical manifestations in men.

Anogenital HPV infections in men exhibit significant heterogeneity in lesion morphology, localization, and genotype distribution. HR HPV genotypes were detected in a notable proportion of benign lesions, underscoring their potential role in disease progression. INNO-LiPA proved superior in diagnostic accuracy, highlighting the need for standardized and cost-effective diagnostic approaches for men. Further research is crucial to elucidate HPV's clinical impact in men and inform prevention and treatment strategies.

Objectives: This study aimed to compare the imaging findings associated with the recurrence of HPV-positive and HPV-negative oropharyngeal squamous cell carcinoma (OPSCC). Methods: In total, 68 patients (51 men; mean age, 64.4 years; age range, 41-86 years; 48 HPV-positive patients and 20 HPV-negative patients) with histopathologically proven OPSCC who underwent CT, MRI, and 18F-FDG-PET/CT before treatment between October 2014 and July 2022 were enrolled in this study. The imaging findings were retrospectively evaluated and statistically compared. Results: HPV-positive OPSCC had a significantly lower recurrence rate compared with that of HPV-negative OPSCC (p < 0.01). Among HPV-positive OPSCCs, patients with recurrence were considerably older than those without recurrence (p < 0.05); however, the T and N categories did not differ between the two groups. Meanwhile, among HPV-negative OPSCCs, the T and N categories were associated with recurrence (p < 0.05). Furthermore, the attenuation on contrast-enhanced CT (p < 0.05) and signal intensity on contrast-enhanced T1-weighted images (p < 0.05) of nodal metastases were significantly lower in recurrence patients compared to those in nonrecurrence patients. Cystic change in nodal metastases in HPV-positive and HPV-negative OPSCCs were similar in patients with and without recurrence. Conclusions: The T and N categories were associated with recurrence in HPV-negative OPSCC but not in HPV-positive OPSCC. Prognostic factors differed significantly between HPV-positive and HPV-negative OPSCC.

The rising incidence of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) necessitates advancements in risk stratification to optimize treatment outcomes and improve the quality of life for patients. Despite its favorable prognosis compared to HPV-negative OPSCC, current clinical staging and biomarkers, such as p16 status, are limited in their ability to distinguish between high- and low-risk patients within HPV-associated OPSCC. This limitation results in the overtreatment of low-risk patients, exposing them to unnecessary toxicity, and the undertreatment of high-risk patients who require more aggressive interventions. This review critically evaluates current stratification methods, including clinical assessments, de-escalation trials, and candidate molecular biomarkers for risk stratification. Emerging approaches such as immune markers, viral genomic integration patterns, and other molecular markers offer promising avenues for enhanced prognostic accuracy. By integrating advanced risk stratification methods, tailored treatment approaches may one day be developed to balance oncologic efficacy with reduced treatment-related morbidity. This review underscores the need for continued research into predictive biomarkers and adaptive treatment strategies to better address the diverse risk profiles of HPV-associated OPSCC patients.

To investigate the impact of county-level social vulnerability on patients' decision to refuse recommended surgical treatment.

Retrospective cohort analysis conducted on HNSCC cases documented in the latest available SEER databases from 2000 to 2020; various demographic, including county of residence, and disease-related variables were collected. CDC's Social Vulnerability Index (SVI) was assigned based on patients' county of residence, and patients were subsequently categorized into four SVI quartiles. Pearson chi-square tests and binomial logistic regression was conducted to determine the impact of variables on patients' refusal of surgical treatment.

Among 83,184 patients, 2.6% (2,165) refused surgical intervention recommended by their physician as part of treatment. Social vulnerability (higher SVI), male sex, older age, more advanced disease stage, belonging to non-Hispanic Black or Native Hawaiian/Asian Pacific Islander Race and Origin, and single marital status were associated with higher likelihood of refusing surgery.

SVI is a significant factor in the refusal of recommended surgical treatment in HNSCC patients. Advanced disease stages and social vulnerability appear to interplay, influencing treatment decisions. Culturally competent care and support for socially vulnerable patients may mitigate disparities in treatment acceptance, potentially improving survival outcomes.

3 Laryngoscope, 2025.

Introduction The incidence of oropharyngeal squamous cell carcinoma (OPSCC) has been increasing worldwide. High-risk human papillomavirus (HPV) infection is now a well-recognised risk factor for oropharyngeal cancers. However, the information regarding the prevalence and outcome of HPV-related OPSCC is sparse in India. The study was conducted to identify the frequency of HPV infection in oropharyngeal cancer and also to study the treatment response and survival according to HPV positivity and p16INK4A expression. Materials and methods The study sample consists of 100 paraffin-embedded tissue blocks of histologically proven OPSCC patients who had undergone treatment at a tertiary cancer centre in Kerala, India, from January 2010 to December 2012. The patients' medical records were examined to obtain demographic data, information on habits, and clinical, histopathological, and treatment information. Follow-up information on disease status and vital status was collected until May 2023. Paraffin-embedded tissue blocks of these patients were collected from the archives of the Division of Pathology. Immunohistochemistry (IHC) was used to identify p16 expression. HPV DNA was isolated from the paraffin-embedded tissue blocks by polymerase chain reaction. Statistical analysis and results Survival curves were obtained using the Kaplan-Meier method and compared with the log-rank test. The influence of p16 status and HPV DNA positivity on survival and recurrence was assessed using Cox regression. A total of 100 patients diagnosed with oropharyngeal malignancy and their paraffin-embedded blocks were used for the present study. p16 IHC was invalid for three patients, and 16 patients had invalid HPV DNA. Two patients were excluded from survival analysis because they had both invalid HPV DNA and p16 expression. A total of 98 patients were included in the analysis. Out of 98 samples assessed, 47 tested positive for p16 expression, 48 were negative, and three showed invalid results. Among the 98 patients, HPV DNA results were available for 82 patients. HPV DNA positivity was reported in 25 patients, and 57 samples were HPV negative. There was no significant correlation between p16 expression and HPV status. The median follow-up was 134 months (1-160 months). The five-year overall survival (OS) probability was 42.6% (95% confidence interval (CI) 28.49-56.71) and 51.2% (95% CI 35.92-66.48), respectively, for p16-negative and p16-positive tumours (p=0.689). The corresponding figures for five-year disease-free survival (DFS) were 49.0% (95% CI 34.7-63.3) and 51.9% (95% CI 36.62-67.18), p=0.959. The five-year OS for HPV DNA-negative tumours was 45.5% (95% CI 32-59.02) compared to 49.1% (95% CI 28.72-69.48) in HPV DNA-positive tumours. There was an absolute difference of 20% in five-year OS between double-positive and double-negative tumours. Conclusion This study demonstrated a p16 positivity rate of 49.47% and an HPV DNA positivity rate of 30.37%. However, only 15.18% of cases showed double positivity. No significant correlation was observed between p16 expression and HPV status. Double positivity (p16 and HPV positive) was associated with better OS and DFS compared to double-negative (p16 and HPV negative) and single-positive (either p16 positive or HPV positive) cases. This subgroup of patients might benefit from potential de-escalation strategies and should be the target population for future studies.

Studies indicate a strong correlation between the length and degree of alcohol and tobacco use and the risk of oral cancer (OC). However, there has been debate concerning the usage of mouthwashes and associated higher risk of OC for many years. The purpose of this study was to gain insight into how using mouthwash influenced the risk of OC. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol was used when searching the PubMed/MEDLINE, Scopus, and Web of Science databases. Observational studies that addressed the relationship between mouthwash use and OC and involved adult or older adult populations were included. The Newcastle-Ottawa Scale was employed to check the methodological quality, and random effects meta-analysis, along with other subgroup analyses and meta-regression, were utilized to synthesize quantitative data. Out of 5,132 papers identified, 15 case-control studies comprising 6,515 cases and 17,037 controls were included in the review. Seventeen effect measures from these 15 studies were included in the meta-analysis. For individuals who used mouthwash three or more times a day, the pooled OR for OC was 1.00 (95% CI: 0.79-1.26; n = 17 studies). Among those who had used mouthwash for more than 40 years, the OR was 1.30 (95% CI: 1.58-4.82; p = 0.05; n = 2 studies). Some studies suggest that frequent mouthwash use may increase the risk of OC. Given the biological plausibility of this link, we exercise caution in interpreting these findings. It is important to note the limited research on the frequency and duration of mouthwash use. Thus, for the strengthening of the evidence for a possible dose-response effect of mouthwashes on OC risk, we suggest that future research should be focused on the frequency, duration, and substance of mouthwashes in depth.

Assessing the risk of cancer among people living with HIV (PLHIV) in the current era of antiretroviral therapy (ART) is crucial, given their increased susceptibility to many types of cancer and prolonged survival due to ART exposure. Our study aims to compare the association between HIV infection and specific cancer sites in Rwanda. Population-based cancer registry data were used to identify cancer cases in both PLHIV and HIV-negative persons. A probabilistic record linkage approach between the HIV and cancer registries was used to supplement HIV status ascertainment in the cancer registry. Associations between HIV infection and different cancer types were evaluated using unconditional logistic regression models. We performed several sensitivity analyses to assess the robustness of our findings and to evaluate the potential impact of different assumptions on our results. From 2007 to 2018, the cancer registry recorded 17,679 cases, of which 7% were diagnosed among PLHIV. We found significant associations between HIV infection and Kaposi's Sarcoma (KS) (adjusted odds ratio [OR]: 29.1, 95% CI: 23.2-36.6), non-Hodgkin lymphoma (NHL) (1.6, 1.3-2.0), Hodgkin lymphoma (HL) (1.6, 1.1-2.4), cervical (2.3, 2.0-2.7), vulvar (4.0, 2.5-6.5), penile (3.0, 2.0-4.5), and eye cancers (2.2, 1.6-3.0). Men living with HIV had a higher risk of anal cancer (3.1, 1.0-9.5) than men without HIV, but women living with HIV did not have higher risk than women without HIV (1.0, 0.2-4.3). Our study found that in an era of expanded ART coverage in Rwanda, HIV is associated with a broad range of cancers, particularly those linked to viral infections.

Immunosuppressed individuals have elevated risk of virus-related cancers. Identifying cancers with elevated risk in people with HIV and solid organ transplant recipients, 2 immunosuppressed populations, may help identify novel etiologic relationships with infectious agents.

We used 2 linkages of population-based cancer registries with HIV and transplant registries in the United States. Cancer entities were systematically classified according to site and histology codes. Standardized incidence ratios were used to compare risk in people with HIV and solid organ transplant recipients with the general population. For selected cancer entities, incidence rate ratios were calculated for indicators of immunosuppression within each population.

We identified 38 047 cancer cases in solid organ transplant recipients and 53 592 in people with HIV, yielding overall standardized incidence ratios of 1.66 (95% confidence interval [CI] = 1.65 to 1.68) and 1.49 (95% CI = 1.47 to 1.50), respectively. A total of 43 cancer entities met selection criteria, including conjunctival squamous cell carcinoma (people with HIV standardized incidence ratio = 7.1, 95% CI = 5.5 to 9.2; solid organ transplant recipients standardized incidence ratio = 9.4, 95% CI = 6.8 to 12.6). Sebaceous adenocarcinoma was elevated in solid organ transplant recipients (standardized incidence ratio = 16.2, 95% CI = 14.0 to 18.6) and, among solid organ transplant recipients, associated with greater risk in lung and heart transplant recipients compared with recipients of other organs (incidence rate ratio = 2.3, 95% CI = 1.7 to 3.2). Salivary gland tumors, malignant fibrous histiocytoma, and intrahepatic cholangiocarcinoma showed elevated risk in solid organ transplant recipients (standardized incidence ratio = 3.9,  4.7, and  3.2, respectively) but not in people with HIV. However, risks for these cancers were elevated following an AIDS diagnosis among people with HIV (incidence rate ratio = 2.4, 4.3, and  2.0, respectively).

Elevated standardized incidence ratios among solid organ transplant recipients and people with HIV, and associations with immunosuppression within these populations, suggest novel infectious causes for several cancers including conjunctival squamous cell carcinoma, sebaceous adenocarcinoma, salivary gland tumors, malignant fibrous histiocytoma, and intrahepatic cholangiocarcinoma.

Human papillomavirus (HPV) has been implicated in several studies pertaining to oral squamous cell carcinoma (OSCC) in the last several decades. Infection with human papillomavirus (HPV), particularly HPV16 and 18, is the leading cause of squamous cell carcinoma of the neck (SCCHN).

We selected an adequate number of subjects with the same parameters for both the case and the controls based on detailed case histories, specifically taking into account the adverse habits (tobacco in any form and alcohol) that each subject had recorded. The subjects were selected from the Outdoor Patient Department of Kothiwal Dental College and Research Centre. Before commencing the experimental procedure, all the subjects had undergone blood examinations (HB%, CT, BT, RBS, HBsAg, HIV). Group 1 consisted of 40 subjects, whereas Group 2 had 20 subjects.

Human papillomaviruses (HPVs) play an important role in oral cancer, and this research demonstrated a substantial link between HPV-16 and HPV-18 and the disease. Although this research does not allow us to draw any conclusions about cause and effect, our results are consistent with and even expand upon those of previous case-control studies. The presence of HPV causes molecular damage in cells, thereby resulting in cell proliferation and malignant conversions. Therefore, we can conclude that the human papillomavirus significantly contributes to carcinogenesis.

Although the current results are based on a limited sample, they provide strong evidence that a larger study of individuals with head and neck cancer is necessary to make firm conclusions.

The incidence of patients showing neck metastasis and no obvious primary tumor at the initial diagnostic evaluation or neck cancer of unknown primary (NCUP) is rising. It is estimated that a relevant part of these tumors arises in the tonsillar crypts or base of the tongue and are p16+-related. However, today, the detection rate of the primary tumor is suboptimal. Identifying the primary tumor and its biomolecular characterization is essential since it influences the treatment administered, possibly reducing radiation fields and providing de-escalation to primary surgical management. However, p16 IHC (immunohistochemistry) might not be sufficient to diagnose HPV-related OPSCC. The other subset of patients discussed are the HPV-positive patients who have a history of tobacco exposure and/or p53 mutations. Possible factors that could negatively influence the outcomes of these patients are investigated and discussed below. So, this paper aims to analyze the diagnostic, bio-molecular, clinico-radiological, morphological, prognostic and therapeutical aspects of p16-positive OPSCC, highlighting the possible bias that can occur during the diagnostic and prognostic process.

A narrative review was conducted to investigate the biases in the diagnostic and therapeutic process of two groups of patients: those who are p16-positive but HPV-negative patients, and those who are p16-positive and HPV-positive with exposure to traditional risk factors and/or p53 mutations. The keywords used for the literature research included the following: NCUP, OPSCC, p16IHC, HPV testing, p16 positive HPV negative OPSCC, p16 positive HPV positive OPSCC, tonsillectomy, tobacco exposure, p53 mutations, cystic neck metastasis, extranodal extension (ENE), radiotherapy, de-escalation and neck neck dissection.

HPV-positive OPSCC has specific clinico-radiological features. Bilateral tonsillectomy should be considered for the identification of the primary tumor. P16 IHC alone is not sufficient for diagnosing HPV-related OPSCC; additional detection methods are required. The role of tobacco exposure and p53 mutations should be investigated especially in cases of HPV-positive tumors. Extranodal extension (ENE) must be taken into consideration in the prognostic staging of HPV-positive tumors. Surgical primary treatment involving neck dissection (ND) and bilateral tonsillectomy followed by adjuvant radiation may represent the most appropriate approach for N3 cases. Diagnosis, prognosis and therapeutical implications must be addressed considering clinical, biomolecular and morphological aspects. At least today, the numerous biases that are still present influencing the diagnostic and prognostic process do not permit considering de-escalation protocols.

A precise and accurate diagnosis is required in order to adequately stage and manage p16+ OPSCC, particularly with neck metastasis. The role of tobacco exposure and/or p53 mutations must be considered not only in p16+ OPSCC but especially in HPV-positive OPSCC. Until a more accurate diagnosis is possible, ENE should be considered even in p16+HPV+ OPSCC. Primary surgery with unilateral ND and bilateral tonsillectomy might be the treatment of choice given the numerous diagnostic and prognostic pitfalls. Therefore, it is inappropriate and risky to propose de-escalation protocols in routine clinical practice due to the risk of undertreatment.

HPV infection and the type of host microbiota play a role in the formation of HNCs. In contrast to other forms of OSCC, where the relationship between HPV and the cancer is less obvious, HPV-HNSCC is a particular type of oropharyngeal cancer. HPV has infected a stratified squamous epithelium, which includes the throat, mouth, anogenital tract, respiratory tract, and skin on the hands and feet. HPV DNA was found in high amounts in the saliva and gargle samples of patients with HPV-related HNSCC. It has been discovered that the specificity of oral mRNA (HPV) and HPV DNA identification varies from 23 % to 82 % in the identification of OPSCCs. The higher rate of HPV transmission through vaginal-oral compared to penile-oral sexual activity may be the reason for the difference in HPV-positive HNSCC patients between males and females. The researchers postulate that HPV-inactive tumours signify an advanced stage of HPV-positive HNSCC, which explains why there are racial disparities in gene expression that correspond to different disease progressions in Black and White patients. The increase of CD8+ T cells in the cancer microenvironment, linked to P16 activation, extends life expectancy in OSCC. tumour markers methylation caused by HPV and suggested using them as possible HNC biomarkers. Fusobacterium levels are much higher in patients with OSCC, while Actinobacteria phylum and Firmicutes are significantly lower. It also serves as a biomarker for notable variations found in Firmicutes, Actinobacteria, Fusobacteriales, Fusobacteriia, Fusobacterium, and Fusobacteriaceae. Therefore, based on this we evidence, we could investigate the role of oral microbiota as a maker for the HPV associated HNSCC.

Cancer resistance to drugs and chemotherapy is a problem faced by public health systems worldwide. Repositioning antimicrobial peptides could be an efficient strategy to overcome that problem. This study aimed at repurposing antimicrobial peptides PepGAT and PepKAA for cancer treatment. After screening against several cancers, PepGAT and PepKAA presented IC50 values of 125.42 and 40.51 μM at 72 h toward colorectal cancer (CRC) cells. The mechanisms of action revealed that both peptides induced cell cycle arrest in G2/M and drove HCT-116 cells to death by triggering apoptosis. qPCR analysis revealed that peptides modulated gene expression in apoptosis, corroborating the data from caspase 3/7 and flow cytometry experiments. Yet, peptides induced ROS overaccumulation and increased membrane permeabilization, pore formation, and loss of internal content, leading to death. Additionally, peptides were able to inhibit cell invasion. Previous studies from the same group attested to no toxicity to normal human cells. Thus, PepGAT and PepKAA have great potential as anticancer molecules.

This study presents a comparative analysis of molecular docking data, focusing on the binding interactions of the natural compounds apigenin and luteolin with the proteins TP-53, pRb, and APOBEC, in comparison to conventional pharmacological ligands. Advanced bioinformatics techniques were employed to evaluate and contrast binding energies, showing that apigenin and luteolin demonstrate significantly higher affinities for TP-53, pRb, and APOBEC, with binding energies of -6.9 kcal/mol and -6.6 kcal/mol, respectively. These values suggest strong potential for therapeutic intervention against HPV-16. Conventional ligands, by comparison, exhibited lower affinities, with energies ranging from -4.5 to -5.5 kcal/mol. Additionally, protein-protein docking simulations were performed to assess the interaction between HPV-16 E6 oncoprotein and tumor suppressors TP-53 and pRb, which revealed high binding energies around -976.7 kcal/mol, indicative of their complex interaction. A conversion formula was applied to translate these protein-protein interaction energies to a comparable scale for non-protein interactions, further underscoring the superior binding potential of apigenin and luteolin. These findings highlight the therapeutic promise of these natural compounds in preventing HPV-16-induced oncogenesis, warranting further experimental validation for clinical applications.

Oral and oropharyngeal cancer have low survival rates, and incidence continues to increase.

To determine whether soluble CD44 and total protein (TP) are useful for monitoring head and neck cancer recurrence, either used in a point-of-care (POC) test or as individual laboratory-based biomarkers.

This multi-institutional nonrandomized clinical trial testing a novel diagnostic/screening assay took place across the University of California, San Diego; Johns Hopkins University; the Greater Baltimore Medical Center; New York University; and the San Diego Veterans Affairs Hospital. Patients with newly biopsy-proven, untreated oral cavity and oropharyngeal cancer were enrolled. Patients were enrolled April 2017 to April 2019, and data were analyzed December 2022 to June 2023.

POC salivary oral rinse test.

Oral rinses were collected at pretreatment baseline and 3, 6, 12, and 18 months after completion of therapy; participants were then followed up for 3 years to define disease status. Associations of baseline characteristics with a positive test were evaluated by Fisher exact test. The association of a positive value on the CD44 or TP test with progression-free survival was evaluated in an adjusted multivariable proportional hazards model.

Of 172 patients enrolled, the mean (SD) age was 62.5 (10.2) years, and 122 (70.9%) identified as male. Additionally, 92 patients (53.3%) had never smoked, 99 (57.6%) formerly or currently drank alcohol, and 113 (65.7%) presented with oropharyngeal cancers, which were positive for human papillomavirus in 95 (84.1%). Tumor site was associated with test results at baseline; patients with oral cavity cancer had a higher baseline positive POC test rate (47 of 51 [92.2%]) compared to patients with oropharyngeal cancer (85 of 110 [77.3%]). Using Cox regression models with CD44 or TP level as a time-varying covariate, a higher CD44 level showed a statistically significant association with a higher hazard of recurrence (hazard ratio, 1.06; 95% CI, 1.00-1.12), though the TP level was not statistically significant. In multivariate adjusted analysis, higher CD44 and TP levels were associated with increased hazard ratios of recurrence of 1.13 (95% CI, 1.04-1.22) and 3.51 (95% CI, 1.24-9.98), respectively.

In this multi-institutional nonrandomized clinical trial of an assay, posttreatment longitudinal monitoring for elevated salivary CD44 and TP levels using an enzyme-linked immunosorbent assay-based laboratory test identified patients at increased risk of future cancer recurrence. The CD44 and TP rapid POC test holds some promise, but further development is needed for this indication.

ClinicalTrials.gov Identifier: NCT03148665.

Increased sexual activity is associated with higher human papillomavirus (HPV) rates; however, there is a lack of analysis comparing the sexual history of patients with HPV positive and HPV negative oropharyngeal cancer (OPC).

In this meta-analysis, PubMed, Scopus, and CINAHL were searched for articles that included patients with OPC and reported information regarding HPV status and either history of oral sex, number of sexual partners, or sexually transmitted infections (STI).

A total of 11 studies were included with 3296 patients with OPC. Patients with HPV positive OPC were more likely than patients with HPV negative OPC to report a history of oral sex (92%, 95% CI: 87.0-97.0 vs. 74.5%, 95% CI: 50.6-98.4, p < 0.0001), higher mean number of sexual partners (18.4 partners, 95% CI: 1.5-35.4 vs. 7.2 partners, 95% CI: 1.0-13.4, p < 0.0001), and more frequent history of STI (23.7%, 95% CI: 18.4-29.0 vs. 8.8%, 95% CI: 4.7-12.8, p = 0.0001).

Compared to patients with HPV negative OPC, our analysis shows a larger proportion of patients with HPV positive OPC had participated in oral sex, had a higher number of sexual partners, and had a higher proportion of STI history.

Originally devised for cancer control, mRNA vaccines have risen to the forefront of medicine as effective instruments for control of infectious disease, notably their pivotal role in combating the COVID-19 pandemic. This review focuses on fundamental aspects of the development of mRNA vaccines, e.g., tumor antigens, vector design, and precise delivery methodologies, - highlighting key technological advances. The recent, promising success of personalized mRNA vaccines against pancreatic cancer and melanoma illustrates the potential value for other intractable, immunologically resistant, solid tumors, such as glioblastoma, as well as the potential for synergies with a combinatorial, immunotherapeutic approach. The impact and progress in human cancer, including pancreatic cancer, head and neck cancer, bladder cancer are reviewed, as are lessons learned from first-in-human CAR-T cell, DNA and dendritic cell vaccines targeting glioblastoma. Going forward, a roadmap is provided for the transformative potential of mRNA vaccines to advance cancer immunotherapy, with a particular focus on the opportunities and challenges of glioblastoma. The current landscape of glioblastoma immunotherapy and gene therapy is reviewed with an eye to combinatorial approaches harnessing RNA science. Preliminary preclinical and clinical data supports the concept that mRNA vaccines could be a viable, novel approach to prolong survival in patients with glioblastoma.

Oral human papillomavirus (HPV) infection and the oral microbiome are associated with oropharyngeal cancer. However, population-based data on the association of oral microbiome with oral HPV infection are limited.

A cross-sectional analysis of 5496 20-59-year-old participants in the 2009-2012 National Health and Nutrition Examination Survey was performed. Associations with oral HPV infection were assessed using multivariable logistic regression for oral microbiome α-diversity (within-sample diversity), and using principal coordinate analysis and permutational multivariate analysis of variance for β-diversity (between-sample heterogeneity).

Overall, for α-diversity, a lower number of observed amplicon sequence variants (adjusted odds ratio [aOR] = 0.996; 95% confidence interval [CI] = .992-.999) and reduced Faith's phylogenetic diversity (aOR = 0.95; 95% CI = .90-.99) were associated with high-risk oral HPV infection. β-diversity showed differentiation of oral microbiome community by high-risk oral HPV infection as measured by Bray-Curtis dissimilarity (R2 = 0.054%; P = .029) and unweighted UniFrac distance (R2 = 0.046%; P = .045). There were differential associations when stratified by sex.

Both oral microbiome α-diversity and β-diversity were marginally associated with oral HPV infection. Longitudinal studies are needed to characterize the role of the microbiome in the natural history of oral HPV infection.

Oral cancer is one of the most common cancers in China and seriously threaten life and health of Chinese people. We analysed the trends and disparities of oral cancer mortality rates and the disease burden of oral cancer in China from 2006 to 2021 to provide a reference for its prevention and control.

Annual death data for oral cancer was gleaned from the China Death Surveillance Database. The age-standardized mortality rate (ASMR), annual percentage change (APC), and average APC (AAPC) were used to analyze the trend of mortality. Loss of life expectancy (LLE) and years of life lost (YLL) were adopted to assess disease burden.

From 2006 to 2021, the overall ASMR of oral cancer lightly declined (AAPC: - 0.97%; 95% CI: - 1.89%, - 0.04%), and the similar trend was observed among females (AAPC: - 1.22%; 95% CI: - 1.89%, - 0.55%). The ASMR of males was 2.31-3.16 times higher than that of females per year. The median of LLE for overall, males and females caused by oral cancer from 2006 to 2021 were 0.05, 0.06 and 0.03 years, respectively. There was a decrease of standardized YLL rate from 2006 to 2021 for overall (AAPC: - 1.31%, 95% CI: - 2.24% ~  - 0.37%) and for female (AAPC: - 1.63%, 95% CI: - 2.30% ~  - 0.95%). ASMR in urban areas was 1.02-1.28 times higher than that in rural areas from 2006 to2011, but 0.85-0.97 times lower in urban areas than that in rural areas from 2018 to 2021. The disease burden was higher in urban areas than in rural areas in 2006, whereas the reverse was observed in 2021.

There are severe health gaps and disparities in trends between sexes and different areas in China. Males and rural populations need to be focused on targeted interventions for the main influencing factors.

France has the sixth highest incidence of oropharyngeal cancer (OPC) in Europe, but the epidemiological impact of high-risk HPV (HR-HPV) remains poorly documented. The objective of our study was to assess the proportion of OPCs caused by HR-HPV in Paris, and its suburbs, over the four past decades. This area accounts for almost one-fifth of the total population of France.

OPCs diagnosed in 1981, 1986, 1991, 1996, 2001, 2006, 2011, 2016 and 2020/2021 in two of the main referral cancer centers for HNCs in Paris and its suburbs were retrieved from the tumor biobanks. HPV status was determined by p16-staining and HPV-DNA detection. Samples were considered HPV-driven if both assays were positive. Results were compared to the French cancer registry data.

Samples from 697 OPC patients were assessed (including 82 % of all samples diagnosed in 2001, 2006, 2011, 2016, 2021). The proportion of HPV-driven cases rose from 2.7 % to 53 % between 1981 and 2021. HPV16 was the dominant genotype during the study period. Of patients with HPV-driven OPC, 81 % were male and 42 % were smokers versus 80 % and 92 % in their HPV-negative counterparts. The age of OPC patients increased significantly, during the study period, independent of their HPV status CONCLUSION: The proportion of HPV-driven OPCs has significantly increased in Paris and its suburbs, during the last four decades. OPCs has become the 2nd predominant type of head and neck cancer, in France. This may be linked to the rise in HPV-driven cases and the decrease of tobacco and alcohol consumption in men.

Human papillomavirus (HPV) proteins may elicit antibody responses in the process toward HPV-related malignancy. However, HPV seroepidemiology in noncervical HPV-related cancers remains poorly understood, particularly in populations with a high prevalence of human immunodeficiency virus (HIV). Using a glutathione S-transferase-based multiplex serology assay, antibodies against E6, E7 and L1 proteins of HPV16 and HPV18 were measured in sera of 535 cases of noncervical HPV-related cancers (anal (n = 104), vulval (n = 211), vaginal (n = 49), penile (n = 37) and oropharyngeal (n = 134)) and 6651 non-infection-related cancer controls, from the Johannesburg Cancer Study that recruited Black South African with newly diagnosed cancer between 1995 and 2016. Logistic and Poisson regression models were used to calculate adjusted odds ratios (aOR) and prevalence ratios (aPR) and 95% confidence intervals (CI) in cases versus controls. HPV16 E6 was more strongly associated with noncervical HPV-related cancers than HPV16 L1 or E7, or HPV18 proteins: anal (females (HPV16 E6 aOR = 11.50;95%CI:6.0-22.2), males (aOR = 10.12;95%CI:4.9-20.8), vulval (aOR = 11.69;95%CI:7.9-17.2), vaginal (aOR = 10.26;95%CI:5.0-21), penile (aOR = 18.95;95%CI:8.9-40), and oropharyngeal (females (aOR = 8.95;95%CI:2.9-27.5), males (aOR = 3.49;95%CI:1.8-7.0)) cancers. HPV16-E6 seropositivity ranged from 24.0% to 35.1% in anal, vulval, vaginal and penile cancer but was significantly lower (11.2%) in oropharyngeal cancer. After adjustment for HIV, prevalence of which increased from 22.2% in 1995-2005 to 54.1% in 2010-2016, HPV16 E6 seropositivity increased by period of diagnosis (aPR for 2010-2016 vs. 1995-2006 = 1.84;95%CI:1.1-3.0). Assuming HPV16 E6 seroprevalence reflects HPV attributable fraction, the proportion of certain noncervical-HPV-related cancers caused by HPV is increasing over time in South Africa. This is expected to be driven by the increasing influence of HIV.

The purpose of this study is to look at how often premalignant oral diseases are among patients who visit a tertiary care center, as well as how often these problems progress to become mouth malignancies.

Between 2017 and 2022, 200 patients at a tertiary care facility who were identified with premalignant oral lesions had their medical records retrospectively examined. Information on lesion features, histological results, and demographics was gathered. Statistical analysis was used to determine the prevalence of premalignant oral lesions and the rate at which these lesions turned into oral malignancies, with a significance threshold of P < 0.05.

The research population's mean age was 55 years (SD ± 10), with a 65% male preponderance. The most prevalent premalignant lesions were leukoplakia (45%), erythroplakia (30%), and oral submucous fibrosis (25%). Remarkably, during follow-up, 40% of patients showed development of premalignant lesions into mouth malignancies. Based on statistical analysis, there were significant correlations (P < 0.05) between dysplastic alterations, age, tobacco use, and the development of oral malignancies from premalignant lesions.

In conclusion, this study highlights the need of early diagnosis and focused therapies in tertiary care settings by offering important insights into the occurrence and evolution of premalignant oral lesions. The results provide important information that may be used to create screening programs and preventive measures that will lessen the incidence of oral cancer.

Circulating tumor human papillomavirus DNA (ctHPV DNA) has shown potential as a biomarker capable of improving outcomes in patients with HPV-related oropharyngeal (OP) cancer. It can be isolated from plasma or saliva, with the latter offering reduced invasiveness and theoretic reduction of lead time.

To perform a systematic review and meta-analysis on the accuracy of salivary ctHPV DNA for detecting HPV-associated OP cancer.

Cochrane Library, Embase, PubMed, and Web of Science databases were searched from inception through October 2023.

All patients who underwent salivary ctHPV DNA testing at presentation for possible or diagnosed HPV-related OP cancer were included. Non-English and review publications were excluded. Two authors independently voted on article inclusion with a third resolving conflicting votes.

Following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines, multiple authors independently abstracted data and assessed bias of included articles. Bivariate random-effects meta-analysis was performed with I2 to assess for study heterogeneity.

Sensitivities, specificities, positive likelihood ratios (PLR), negative likelihood ratios (NLR), and diagnostic odds ratios (DOR) with 95% CIs alongside area under the curve (AUC) of a summary receiver operating characteristic (SROC) curve were calculated. The initial analysis took place throughout December 2023.

Of 440 initially identified articles, 6 met inclusion criteria and demonstrated moderate heterogeneity (I2 = 36%) with low risk of bias and low applicability concerns. Overall, 263 total patients were included with a median (range) age of 58 (39-86) years, and 228 (87%) were male patients. Per updated prognostic staging criteria, localized tumors (ie, stages 1 or 2) comprised most cancers at 139 (77%), whereas advanced ones (ie, stages 3 or 4) comprised the remaining 41 (23%). Pooled sensitivity, specificity, PLR, NLR, and DOR values were 64% (95% CI, 36%-85%), 89% (95% CI, 46%-99%), 11.70 (95% CI, 0.37-77.00), 1.21 (95% CI, 0.08-7.00), and 139.00 (95% CI, 0.05-837.00), respectively. The AUC of the SROC curve was 0.80.

This study supports salivary ctHPV DNA as an acceptably specific test in detecting HPV-associated OP cancer that would benefit from testing in clinical trials prior to real-time implementation.

To examine the association between the human papillomavirus (HPV) infection and overall survival rate in patients with oral cancer.

This retrospective cohort study examined HPV status in 454 patients who were diagnosed with oral squamous cell carcinoma (OSCC) using the records of patients who underwent an initial treatment for OSCC between 2012 and 2021 at our institution as retrieved from the Cancer Registry database. The survival rates of the HPV-positive and HPV-negative groups were assessed and compared, and independent factors associated with survival were analyzed using multivariate Cox regression models.

Of the 454 patients with OSCC included in this study, 73 were excluded for invalid HPV tests. Of the remaining patients, 39 and 342 patients were categorized into HPV-positive and HPV-negative groups, respectively. The prevalence of HPV-positive in the patients with OSCC was 10.2% (95% confidence interval 7.2%-13.2%). The 3-year overall survival rates were 56.2% and 53.9% in the HPV-positive and HPV-negative groups, respectively. The 3-year disease-specific survival rates in the HPV-positive and HPV-negative groups were 60.2% and 56.9%, respectively. The survival differences were not statistically significant. HPV-positive status was not a significant predictor of overall survival in the multivariable Cox regression analyses (p = 0.728).

The prevalence of HPV-positivity among patients with OSCC in the study was 10.2%. No association was found between HPV-positive status and 3-year overall survival in patients with oral cancer.

Level 3.

Despite numerous studies having evaluated the associations between human papillomavirus (HPV) infection and risk of specific cancers other than anogenital tract and oropharyngeal, the findings are inconsistent and the quality of evidence has not been systematically quantified. We aimed to summarise the existing evidence as well as to evaluate the strength and credibility of these associations.

We conducted an umbrella review of systematic reviews and meta-analyses of observational studies. PubMed, EMBASE, and Web of Science were searched from inception to March 2024. Studies with systematic reviews and meta-analyses that examined associations between HPV or HPV-associated genotypes infection and specific cancers were eligible for this review. The quality of the methodology was evaluated using A Measurement Tool to Assess systematic Reviews (AMSTAR). The credibility of the evidence was assessed using GRADE. The protocol was preregistered with PROSPERO (CRD42023439070).

The umbrella review identified 31 eligible studies reporting 87 associations with meta-analytic estimates, including 1191 individual studies with 336,195 participants. Of those, 29 (93.5%) studies were rated as over moderate quality by AMSTAR. Only one association indicating HPV-18 infection associated with an increased risk of breast cancer (odds ratio [OR] = 3.48, 95% confidence interval [CI] = 2.24-5.41) was graded as convincing evidence. There were five unique outcomes identified as highly suggestive evidence, including HPV infection increased the risk of oral squamous cell carcinoma (OR = 7.03, 95% CI = 3.87-12.76), oesophageal cancer (OR = 3.32, 95% CI = 2.54-4.34), oesophageal squamous cell carcinoma (OR = 2.69, 95% CI = 2.05-3.54), lung cancer (OR = 3.60, 95% CI = 2.59-5.01), and breast cancer (OR = 6.26, 95% CI = 4.35-9.00). According to GRADE, one association was classified as high, indicating that compared with the controls in normal tissues, HPV infection was associated with an increased risk of breast cancer.

The umbrella review synthesised up-to-date observational evidence on HPV infection with the risk of breast cancer, oral squamous cell carcinoma, oesophageal cancer, oesophageal squamous cell carcinoma, and lung cancer. Further larger prospective cohort studies are needed to verify the associations, providing public health recommendations for prevention of disease.

National Key Research and Development Program of China, Natural Science Foundation of China, Outstanding Scientific Fund of Shengjing Hospital of China Medical University, and 345 Talent Project of Shengjing Hospital of China Medical University.

Surgery remains a foundation of treatment for locally advanced squamous cell carcinoma of the head and neck. For postoperative patients at high risk of recurrence, however, surgery by itself is not enough, and improvement in survival requires postoperative treatment. Unlike the case with most other malignancies, the standard postoperative treatment for locally advanced squamous cell carcinoma of the head and neck patients with high-risk factors for recurrence is radiotherapy or chemoradiotherapy with cisplatin. However, chemoradiotherapy with cisplatin at a dose of 100 mg/m2 once every 3 weeks has raised discussion over insufficient cisplatin delivery due to high-dose-related toxicity. As a possible solution, a recent randomized trial of the JCOG1008 has proved the non-inferiority of postoperative chemoradiotherapy with weekly cisplatin at a dose of 40 mg/m2 to 3-weekly cisplatin in terms of overall survival. Here, this review article focuses on current evidence and future perspectives of postoperative treatment for locally advanced squamous cell carcinoma of the head and neck.

Human Papilloma Virus (HPV) is considered one of the most common sexually transmitted infections and has been shown to play an important role in the pathogenesis of squamous cell carcinomas (SCC) of the cervix and head and neck. Manifestations of HPV infections can be manifold, ranging from asymptomatic infections to benign or potentially malignant lesions to intraepithelial neoplasms and invasive carcinomas. The heterogeneity of clinical manifestations from HPV infection depends on the interactions between the viral agent and the host, a direct consequence of the ability on the part of HPV is to remain silent and to evade and convey the action of the host immune system. The oral mucosa represents one of the tissues for which HPV has a distinct tropism and is frequently affected by infection. While much information is available on the role that HPV infection plays in the development of SCC in the oral cavity, there is less information on asymptomatic infections and benign HPV-induced oral lesions. Therefore, the purpose of this review is to analyze, in light of current knowledge, the early clinical and bio-humoral prognostic features related to the risk of HPV malignant transformation, focusing on subclinical conditions, benign lesions, and the correlation between oral infection and infection in other districts. The data show that the main risk associated with HPV infection is related to malignant transformation of lesions. Although HPV-driven OPSCC is associated with a better prognosis than non-HPV-driven OPSCC, primary prevention and early detection of the infection and affected genotype are essential to reduce the risk of malignant neoplastic complications and improve the prognosis.

E2F transcription factors (E2Fs) are a group of genes that encode a family of transcription factors. They have been identified as being involved in the tumor progression of various cancer types. However, little is known about the expression level, genetic variation, molecular mechanism, and prognostic value and immune infiltration of different E2Fs in HNSCC.In this study, we utilized multiple databases to investigate the mRNA expression level, genetic alteration, and biological function of E2Fs in HNSCC patients. Then, the relationship between E2Fs expression and its association with the occurrence, progress, prognosis, and immune cell infiltration in patients with HNSCC was evaluated. We found that all eight E2Fs were higher expressed in HNSCC tissues than in normal tissues, and the expression levels of E2F1/2/3/4/5/6/8 were also associated with the stage and grade of HNSCC. The abnormal expression of E2F1/2/4/8 in HNSCC patients is related to the clinical outcome. The expression of E2Fs was statistically correlated with the immune cell infiltration in HNSCC and the infiltration of B cells and CD8+ T cells were positively associated with better OS in HNSCC patients. Furthermore, we verified the E2F2 at the tissue level in the validation experiment. Our study may provide novel insights into the choice of immunotherapy targets and potential prognostic biomarkers in HNSCC patients.

Cytological specimens play a pivotal role in head and neck nodule/mass work up and diagnoses. The specimens´ importance has grown with the onset of personalized medicine and the routine use of molecular markers in the diagnostic work up. The Updates in Head and Neck Cytopathology Short Course ran during the 35th European Congress of Pathology held in Dublin, Ireland, in 2023 and brought together experts in cytopathology, pathology, and related fields to share their expertise and experience in the field of head and neck cytopathology and its future directions. Topics such as a one-stop clinic, the Milan System for Reporting Salivary Gland Cytopathology, next generation sequencing, and human papilloma virus detection in the head and neck area were covered during the short course. These topics are briefly summarized in the present review.

Sex differences in head and neck cancer (HNC) incidence suggest a potential contribution of sex hormones.

To assess the role of exogenous estrogen exposure in the development of HNC in female patients.

This large multicenter cohort study using clinical records from the TriNetX real-world database included 20 years of data (through May 31, 2023) from 87 health care organizations. The TriNetX database was searched for medical records for female patients with and without exogenous estrogen exposure according to their chronological age. Cohort 1 included 731 366 female patients aged 18 to 45 years old with regular oral contraceptive (OC) intake and cohort 2 included 3 886 568 patients in the same age group who did not use OC. Cohort 3 comprised 135 875 female patients at least 50 years old receiving hormone replacement therapy (HRT), whereas cohort 4 included 5 875 270 patients at least 50 years old without HRT. Propensity score matching was performed for the confounders age, alcohol dependence, and nicotine dependence. Data analyses were performed in May 2023.

Diagnosis of HNC (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision: C00-C14), and after propensity score matching (1:1 nearest-neighbor greedy matching), a risk analysis to investigate risk differences and risk ratios (RRs) with a 95% CI.

Among the 718 101 female patients in each of cohorts 1 and 2 (mean [SD] age at diagnosis, 25.9 [6.7] years), those with OC intake had a higher risk of an HNC diagnosis (RR, 1.47; 95% CI, 1.21-1.78) than those without OC use. Among the 131 835 female patients in each of cohorts 3 and 4 (mean [SD] age, 67.9 [12.0] years), those with postmenopausal HRT intake had a lower risk of an HNC diagnosis (RR, 0.77; 95% CI, 0.64-0.92) than those without HRT use.

The findings of this cohort study illustrate a positive association between OC and a negative association between HRT and the development of HNC in female patients. Given the limitations of the TriNetX database, future research should include detailed information on the intake of OC and HRT and reproductive health information (eg, age at menarche/menopause, number of pregnancies) to more accurately define the strength and direction of the possible association between exogeneous estrogen exposure and the development of HNC in female patients.