Evaluation of the Prevalence and Potential Impact of HPV Vaccines in Patients with and Without Oral Diseases: A Ten-Year Retrospective Study.

BACKGROUND: The prevalence of oral human papillomavirus (HPV) in the healthy population and patients with oral diseases such as oral squamous cell carcinoma (OSCC), oral potentially malignant disorders (OPMDs), and oral benign lesions (BL), is not consistently described in the literature, with scarce and often heterogeneous data. In addition, the efficacy of HPV prophylactic vaccines in preventing HPV-related oral disorders has been scarcely investigated. METHODS: The prevalence of HPV and the potential impact of vaccines were analyzed in 1,415 oral rinse specimens, collected over 10 years and grouped into four categories based on histological/clinical diagnosis. RESULTS: HPV prevalence in OSCC, OPMD, and BL patients and in healthy individuals potentially exposed to HPV (HPE) was comparable (12.7 vs. 27.2% vs. 13.5 vs. 9%). Statistical analysis of the vaccine impact involved calculating high and low estimates and showed a significant difference only for the low effect. The nonavalent vaccine had higher low estimates than the bivalent vaccine in OSCC and HPE patients (29.6 vs. 51.9%, p < 0.05; 18.2 vs. 42.4%, p < 0.05), while for OPMD and BL, the frequency of bivalent low estimates was lower than that of quadrivalent and nonavalent (48.6 vs. 68.6%, p < 0.05 and 48.6 vs. 77.1%, p < 0.05; 23.9 vs. 50.7%, p < 0.05, and 23.9 vs. 63.4%, p < 0.05). CONCLUSIONS: This study provided new insights into the prevalence of oral HPV and showed that the nonavalent vaccine may provide better protection than the other vaccines in the presence of an OSCC diagnosis. Conversely, the quadrivalent vaccine may be sufficient to prevent OPMD and BL.

Delayed Complete Clearance of Recalcitrant Warts Due to Intralesional Measles, Mumps, and Rubella: Case Report and Review.

Warts are a prevalent skin condition that can affect people of any age. They are caused by the human papillomavirus (HPV), a double-stranded DNA virus that can cause benign and malignant lesions and remains latent in the host cells, leading to recurrences. Although warts are benign and spontaneous clearance has been reported over the years, they often cause disfigurement, tend to koebnerize, and can be transmitted to others, making adequate and timely treatment important. Several conventional treatments are available, but none works consistently for all patients. Incomplete responses or recurrences are often bothersome to both patients and dermatologists. Moreover, these treatments are often painful, time-consuming, and can cause significant scarring. Immunotherapy, as an alternative, has found a significant place in the treatment of warts because of its non-destructive action, ease of use, and promising results. This paper will discuss a healthy 36-year-old Bosnian male with chronic palmoplantar and periungual warts. Despite undergoing multiple destructive and topical treatments, including electrocautery, cryotherapy, carbon dioxide laser, salicylic acid, glycolic acid, 5-fluorouracil, and imiquimod, he could not achieve significant improvement in his skin condition. Subsequent treatment with the intralesional measles, mumps, rubella (MMR) vaccine also showed little improvement during treatment. However, three months without further treatment, the patient reported complete resolution of the warts. Follow-up confirmed the clearance with no recurrence and minor post-inflammatory hypopigmentation. Our patient's delayed response to the MMR vaccine aligns with findings from other studies indicating that the body's immune response may take time to manifest fully.

The role of cGAS-STING signaling in the development and therapy of head and neck squamous cell carcinoma.

The cGAS-STING signaling pathway plays a critical role in innate immunity and defense against viral infections by orchestrating intracellular and adaptive immune responses to DNA. In the context of head and neck squamous cell carcinoma (HNSCC), this pathway has garnered significant attention due to its potential relevance in disease development and progression. HNSCC is strongly associated with risk factors such as smoking, heavy alcohol consumption, and human papillomavirus (HPV) infection. The presence or absence of HPV in HNSCC patients has been shown to have a profound impact on patient survival and prognosis, possibly due to the distinct biological characteristics of HPV-associated tumors. This review aims to provide a comprehensive overview of the current therapeutic approaches and challenges in HNSCC management, as well as the involvement of cGAS-STING signaling and its potential in the therapy of HNSCC. In addition, by advancing the present understanding of the mechanisms underlying this pathway, Activation of cGAS-STING-dependent inflammatory signaling downstream of chromosomal instability can exert both anti-tumoral and pro-tumoral effects in a cell-intrinsic manner, suggesting individualized therapy is of great importance. However, further exploration of the cGAS-STING signaling pathway is imperative for the effective management of HNSCC.

Histologic spectrum and outcome of Human papillomavirus (HPV)-associated oral cavity squamous cell carcinoma: a single center experience and a survey of The Cancer Genome Atlas (TGCA) cohort.

While high-risk human papillomavirus (HPV) serves as an essential pathogen and an important prognostic and predictive biomarker for oropharyngeal squamous cell carcinoma, it occurs at low frequency (2.2-6%) in oral cavity squamous cell carcinoma (OCSCC). To date, the pathologic features of HPV-associated OCSCC (HPV( +)-OCSCC) have been sparsely reported and its prognosis is not well-defined. We herein described detailed clinicopathologic features and outcomes of a retrospective series of 27 HPV( +)-OCSCC, including 13 from Memorial Sloan Kettering Cancer Center (MSKCC) and 14 from The Cancer Genomic Atlas program (TCGA). The frequency of HPV positivity in OCSCC was 0.7% in MSKCC cohort and 4.9% in TCGA cohort. Although HPV( +)-OCSCC was predominantly non-keratinizing (in 81%) with various degree of maturation, its histologic spectrum was expanded to include keratinizing subtype (19%), adenosquamous carcinoma (7%), and papillary architecture (subtype, 7%). HPV( +)-OCSCC predominantly affected male patients (male:female ratio = 12.5:1) and (ex) smokers (77%). It might occur in mandibular mucosa, floor of mouth, tongue, retromolar trigone, buccal mucosa, maxillary mucosa, or hard palate. In oral cavity, positivity of HPV by RNA in situ hybridization was required, and p16 immunohistochemistry alone was insufficient to confirm the HPV + status. The positive predictive value of p16 immunopositivity in detecting HPV infection was 68%. HPV-positivity did not appear to affect outcomes, including disease specific survival and progression free survival in OCSCC.

Palladium catalysed cross coupling reactions on 2,3-isoxazol-17α-ethynyltestosterone, their anti-cancer activity, molecular docking studies and ADMET analysis.

In the current study, the Sonogashira coupling reaction of danazol with aryl halides was carried out, yielding new aryl substituted danazol derivatives. The synthetic compounds were examined for anti-cancer potential on the HeLa human cervical cancer cell line, and they showed promising cytotoxic action. Synthesized compounds 2, 4 and 5 inhibited the growth of HeLa cervical cancer cells, potentially making them effective anti-cancer drugs in the future. Furthermore, molecular docking studies were performed to evaluate the inhibitory impact of danazol derivatives on the Human Papillomavirus (HPV) target protein (1F9F). The docking results showed a significant inhibitory action against the cervical cancer protein (1F9F). The binding energy (ΔG) values of 1, 2, 3, 4 and 5 against the protein 1F9F were -8.01, -8.70, -9.43, -9.58 and -9.75 kcal/mol, indicating a high affinity of the synthesized compounds to bind with the HPV target proteins compared to their parent compound danazol (1). ADMET analyses of all derivatives have also been carried out.

Anal carcinoma - exploring the epidemiology, risk factors, pathophysiology, diagnosis, and treatment.

Anal carcinoma is a relatively rare tumor that accounts for approximately 2% of gastrointestinal malignancies and less than 7% of anorectal cancers. Most anal tumors originate between the anorectal junction and the anal verge. Risk factors for the disease include human papillomavirus infection, human immunodeficiency virus, tobacco use, immunosuppression, female sex, and older age. The pathogenesis of anal carcinoma is believed to be linked to human papillomavirus-related inflammation, leading to dysplasia and progression to cancer. Squamous cell carcinoma is the most common type of anal tumor, with an annual incidence of approximately 1 to 2 per 100000 persons. Treatment regarding anal cancer has emerged over time. However, chemoradiation therapy remains the mainstay approach for early localized disease. Patients with metastatic disease are treated with systemic therapy, and salvage surgery is reserved for disease recurrence following chemoradiation. This article aims to provide background information on the epidemiology, risk factors, pathology, diagnosis, and current trends in the management of anal cancer. Future directions are briefly discussed.

The significance of uterine artery embolization in the treatment of utero-cervical cancer: A single case report.

Key Clinical Message: Uterine artery embolization demonstrated significant efficacy in the treatment of utero-cervical cancer. This minimally invasive procedure holds promise as a valuable adjunct therapy, potentially offering improved outcomes and reduced morbidity in select cases. Further research is warranted to validate its broader clinical utility. Abstract: Vaginal bleeding is a common complication of Cervical cancer that can be considered a critical emergency. Conventional hemostatic treatments may occasionally help reduce the bleeding but are not an effective long-term solution. Uterine Artery Embolization, a minimally invasive intervention, can halt the bleeding, achieving hemostasis, while removing many of the complications that alternative interventions carry. We outline a case study of a patient with extensive vaginal bleeding who had uterocervical malignancy and talk about the benefits of uterine artery embolisation for therapeutic management.

Head-to-head comparison of two human papillomavirus vaccines for efficacy against cervical intraepithelial neoplasia grade 3 and adenocarcinoma in situ-population-based follow-up of two cluster-randomized trials.

Introduction: We report head-to-head comparison of the bivalent and quadrivalent HPV vaccine efficacies against immediate precursors of cervical cancer from 15 years' country-wide cancer registry follow-up of phase III trial cohorts and an age-aligned cohort of unvaccinated women. Methods: These individually and/or clusterrandomized cohorts of HPV6/11/16/18- and HPV16/18-vaccinated and unvaccinated women were enrolled, respectively, in 2002, 2004, and 2003/2005. The trial cohorts comprised initially 16- to 17-year-old HPV6/11/16/18-vaccinated FUTURE II (NCT00092534) participants (866) and HPV16/18-vaccinated PATRICIA (NCT00122681) and 012 trial (NCT00169494) participants (2,465), and 16,526 initially 16- to 19-year-old unvaccinated controls. After active 4-year clinical follow-up, passive, country-wide Finnish Cancer Registry (FCR) follow-up for cervical intraepithelial neoplasia grade 3 (CIN3) and adenocarcinoma in situ (AIS) was based on consented use of unique personal identifiers and started 6 months after the end of the FUTURE II and PATRICIA trials in 2007 and 2009, and ended at the end of 2019. The follow-up with altogether 229,020 follow-up years was age-aligned to ensure that similarly aged cohorts were passively followed up for 15 years post=vaccination for the intention-to-treat analyses of vaccine efficacy. Results: Overall, we identified 5 and 16 CIN3 (no AIS) cases in the HPV6/11/16/18 and HPV16/18 cohorts, respectively, during the FCR-based follow-up. In the unvaccinated cohort, we identified 281 CIN3 cases, 20 AIS cases, and 13 cases with invasive cervical cancer. Vaccine efficacies against CIN3+ were 68.4% and 64.5% for the quadrivalent and the bivalent vaccines, respectively, with overlapping confidence intervals. Discussion: Long-term follow-up of randomized, initially adolescent HPV-vaccinated and unvaccinated cohorts shows, in this head-to-head setting, that the bivalent and quadrivalent HPV vaccines are equally effective against immediate precursors of cervical cancer.

Prevalence of human papillomavirus and cervical lesions among elderly women: an unignored challenge to cervical cancer prevention.

The prevalence of human papillomavirus (HPV) genotype and cervical neoplasia in women older than 64 years, who are outside the age demographic of cervical cancer screening in China, has been under-researched. This study conducts a retrospective analysis of women from a tertiary hospital in Guangzhou, with the aim to offer valuable insights for cervical cancer prevention and control in elderly women. The study incorporated 876 women, all aged 64 and above. In this age bracket, the prevalence rate of any HPV genotype was found to be 19.27%. The top six HR HPV genotypes were HPV 16, HPV 52, HPV 58, HPV 31, HPV 33, and HPV 18. The persistence rate of any HPV type over a 24-month period in this age group was as high as 33.33%. Among women over 64, around 16.47% of HPV-positive patients were diagnosed with cervical cancer. HPV 58 infection was the most substantial risk factor for histological CIN2+ (OR 3.556; 95% CI, 1.107-11.415; p = 0.032) in women over 64 years of age with HPV-positive/NILM status. In conclusion, the burden of HPV infection is significant among women over 64 years in Guangzhou. Re-evaluation of cervical cancer screening strategies for women after the age of 64 is imperative. Moreover, the HPV 16/18/52/58 genotype model could serve as an alternative triage approach to identify histological CIN2+ among elderly women with HPV-positive/NILM status.

Elderly women exhibit an elevated risk of contracting HPV infection and developing cervical lesions.HPV 58 is notably associated with the progression of CIN2+ among women aged above 64 years with HPV-positive/NILM status.HPV 16/18/52/58 genotype model presents an alternative triage approach for identifying CIN2+ among women aged above 64 years with HPV-positive/NILM status.

Population-based age- and type-specific prevalence of human papillomavirus among non-vaccinated women aged 30 years and above in Germany.

BACKGROUND: A persisting high-risk human papillomavirus (HR-HPV) infection is causal for cervical cancer; however, there is limited population-based data on the prevalence of HPV infections in Germany. We assessed the age and type-specific HPV prevalence, and associated risk factors in HPV unvaccinated women aged 30 and above. METHODS: The MARZY prospective population-based cohort study was conducted between 2005 and 2012 in Mainz and Mainz-Bingen, Germany. Eligible women were randomly recruited from population registries and invited for cervical cancer screening (n = 5,275). A study swab (liquid-based cytology) was taken and HPV testing was performed with GP5+/6 + polymerase chain reaction (PCR) followed by genotyping. We assessed HPV types as HR-HPV, 'moderate' risk and low-risk (LR-HPV). Logistic regression was performed to identify factors associated with HPV infection, stratified by HPV types. RESULTS: 2,520 women were screened with a valid PCR result. Overall HPV prevalence was 10.6% (n = 266), with 6.5% HR-HPV positive (n = 165), 1.5% 'moderate' risk type (n = 38) and 3.3% LR-HPV type (n = 84) positive. 8.9% had a single infection (n = 225) and 1.6% had multiple types (n = 41). The most common HR-HPV types were 16, 56, 52 and 31 and LR-HPV 90 and 42. Of 187 HR-HPV infections detected (among 165 women), 55.1% (n = 103) were with HPV types not covered by available bivalent or quadrivalent HPV vaccines. About 23% (n = 43) were of types not covered by the nonavalent vaccine (HPV 35, 39, 51, 56, 59). The HR and LR-HPV prevalence were highest in the age group 30-34 years (HR 9.8%, 'moderate' risk 3.0% and LR 5.6%), decreasing with increasing age. HR-HPV prevalence in women with normal cytology was 5.5%. In women with a high-grade squamous intraepithelial lesion (HSIL), prevalence was 66.7%. Women currently not living with a partner and current smokers had increased chances of an HR-HPV infection. CONCLUSION: The overall population-based HPV prevalence was relatively high. An important share of prevalent HR-HPV infections constituted types not covered by current HPV vaccines. With the advent of HPV screening and younger vaccinated cohorts joining screening, HPV types should be monitored closely, also in older women who were not eligible for HPV vaccination.

HPV-ferroptosis related genes as biomarkers to predict the prognosis of cervical cancer.

BACKGROUND: Ferroptosis can be used as a powerful predictor of cancer prognosis. HPV persistent infection is the main cause of cervical cancer, so it is very important to improve the prognosis of patients. Therefore, it is necessary to explore the value of HPV-ferroptosis related genes as prognostic biomarkers of cervical cancer patients. METHODS: In this study, differentially expressed HPV-ferroptosis related genes were obtained from GSE7410, HPV gene set crossed with iron death genes. Five HPV-ferroptosis related genes with prognostic features were finally identified: CYBB, VEGFA, CKB, EFNA1 and HELLS. Multifactorial Cox regression was applied to establish and validate the prognostic model, and drug susceptibility and immune infiltration analyses were also performed. RESULTS: The prognostic model was validated in the training set (TCGA) and validation set (GSE44001). Kaplan-Meier curves reveal significant differences in overall survival (OS) between high-risk and low-risk groups. Receiver operating characteristic (ROC) curve reflects the stability and accuracy of the prognostic model established in this study. In terms of immune function, T cell costimulation was better in the low-risk group than in the high-risk group (P < 0.01). The therapeutic effects of cisplatin, paclitaxel, docetaxel and cyclophosphamide, commonly used chemotherapy drugs for cervical cancer, are better in the high-risk group than in the low-risk group (P < 0.001). CONCLUSION: HPV-ferroptosis related gene prognostic model not only has good stability and accuracy in predicting the prognosis of cervical cancer patients, but also has certain guiding value for clinicians in terms of drug sensitivity and immune microenvironment.

Natural Small Molecule Compounds Targeting Wnt Signaling Pathway Inhibit HPV Infection.

BACKGROUND: High-risk human papillomavirus (HPV) infection is a major risk factor of HPV-related tumors, especially cervical cancer. To date, there is no specific drug for the treatment of HPV infection. PURPOSE: To explore the role of canonical Wnt signaling pathway in HPV16 infection and to screen inhibitors against HPV16 infection from natural small molecule compounds targeting the canonicalWnt pathway. METHODS: Wnt pathway inhibitor IWP-2 and FH535 were used to inhibit Wnt/ß-catenin signaling pathway. HPV16-GFP pseudovirus infectivity were analyzed by fluorescence microscopy and fluorescence activated cell sorting. A small molecule screening of a total of CFDA-approved 29 natural compounds targeting the Wnt pathway was performed. RESULTS: Wnt signaling pathway inhibitor suppressed HPV16-GFP pseudovirus infection in HaCat cells. Natural small molecule compounds screening identified 6-Gingerol, gossypol, tanshinone II2A, and EGCG as inhibitors of HPV16-GFP pseudovirus infection. CONCLUSION: Wnt signaling pathway is involved in the process of HPV infection of host cells. 6-Gingerol, gossypol, tanshinone II2A, and EGCG inhibited HPV16-GFP pseudovirus infection and suppressed Wnt/ß-catenin pathway in HaCat cells.

Interaction of High- and Low-Risk Human Papillomavirus Genotypes is Associated with a Reduced Risk of Developing Cervical Cancer.

INTRODUCTION: Cervical cancer is among the most common types of cancer in women and is associated with human papillomavirus (HPV) infection. The association between cervical cancer and high-risk HPV infection has been well documented. However, the effect of simultaneous infection with high- and low-risk HPV or low-risk HPV alone on the risk of developing cervical malignancy remains unanswered in guidelines. METHOD: We investigated the association of high and low-risk HPVs (HR or LR) genotypes with cervical carcinoma risk and pathological and cytological information in cases recruited from a population-based cohort study of 790 patients. Correlation matrix and t-test were used for analysis. RESULTS: The percentage of HR+LR and HR-HPV16/18 were 9.30% and 11.20% in class II, 7.15% and 7.10% in class IV, and 7.15% and 5.80% in As-CUS smears. Interestingly, concurrent infection with HR-HPV and LR-HPV types led to a significant reduction in the risk of developing malignancy compared to the high-risk group (OR=0.3 (0.098-0.925), pvalue=0.04). The percentage of individuals with cervical malignancy was 10.2% and 28.2% within the co-infected and the HR-HPV participants. CONCLUSION: Our findings suggest that simultaneous infection with high- and low-risk HPV may reduce the risk of cervical malignancy.

Ranking the attribution of high-risk genotypes among women with cervical precancers and cancers: a cross-sectional study in Ningbo, China.

BACKGROUND: The region-specific importance of carcinogenic HPV genotypes is required for optimizing HPV-based screening and promoting appropriate multivalent HPV prophylactic vaccines. This information is lacking for Ningbo, one of the first cities of China's Healthy City Innovation Pilot Program for Cervical Cancer Elimination. Here, we investigated high-risk HPV (HR-HPV) genotype-specific distribution and attribution to biopsy-confirmed cervical intraepithelial neoplasia grade 2 or worse (CIN2+) before mass vaccination in Ningbo, China. METHODS: A total of 1393 eligible CIN2+ archived blocks (including 161 CIN2, 1107 CIN3, and 125 invasive cervical cancers [ICC]) were collected from 2017 to 2020 in Ningbo. HR-HPV DNA was genotyped using the SPF10-DEIA-LiPA25 version 1 detection system and the SureX HPV 25X Genotyping Kit. Genotype-specific attribution to CIN2+ was estimated using a fractional contribution approach. RESULTS: Ranking by the attributable proportions, HPV16 remained the most important genotype in both cervical precancers and cancers, accounting for 36.8% of CIN2, 53.2% of CIN3, and 73.3% of ICC cases. Among cervical precancers, HPV52 (17.3% in CIN2, 12.7% in CIN3) and HPV58 (13.9%, 14.9%) ranked second and third, while HPV33 (8.3%, 7.9%) and HPV31 (6.5%, 4.1%) ranked fourth and fifth, respectively. However, among ICCs, HPV18 (5.7%) accounted for the second highest proportion, followed by HPV33 (5.4%), HPV58 (4.0%), and HPV45 (3.2%). HPV18/45 together accounted for 46.8% of adenocarcinomas, which was slightly lower than that of HPV16 (47.7%). The remaining HR-HPV genotypes (HPV35/39/51/56/59/66/68) combined accounted for only 6.7% of CIN2, 2.9% of CIN3, and 4.2% of ICC. CONCLUSIONS: With Ningbo's strong medical resources, it will be important to continue HPV16/18 control efforts, and could broaden to HPV31/33/45/52/58 for maximum health benefits. However, different strategies should be proposed for other HR-HPV genotypes based on their lower carcinogenic risks.

Exploring the relationship between adverse childhood experiences and HPV vaccination in a national sample of adults.

BACKGROUND: Over 60 % of U.S. adults report adverse childhood experience (ACE), which correlate with risky health behaviors and lower utilization of healthcare preventive measures, potentially leading to chronic diseases in later life. OBJECTIVE: This study investigates the relationship between ACEs and human papillomavirus (HPV) vaccination in a national U.S. adult sample. PARTICIPANTS AND SETTING: We used data from selected states from the Centers for Disease Control and Prevention Behavioral Risk Factor Surveillance System collected in years 2019 (Mississippi, South Carolina, and Tennessee), 2020 (Georgia, Mississippi, North Dakota, South Carolina), 2021 (Mississippi), and 2022 (Arkansas) (N = 3578, 4392, 904, and 810, respectively). METHODS: We conducted descriptive, univariate, and multivariable regression analysis using SAS 9.4. Independent and dependent variables were ACEs and HPV vaccination, respectively. RESULTS: Individuals with ≥4 ACEs, versus no ACEs, were significantly more likely to report HPV vaccination in 2019, 2020, and 2021 (OR = 1.40, 1.77, 2.80, all p < 0.05 respectively), except in 2022 (OR = 1.54, p = 0.165). In 2019, specific ACE types, emotional abuse, and household mental illness were associated with HPV vaccination, whereas in 2021, emotional abuse, household mental illness, incarcerated household member, and substance abuse in household, and in 2022, emotional abuse was associated with HPV vaccination. CONCLUSIONS: We found mostly positive association between ACEs and HPV vaccination, particularly in initial three years. However, findings in 2022 were not significant, except for emotional abuse. Diverse patterns in relationship between ACEs and HPV vaccination was observed overtime, highlighting the need for consistency in ACEs and HPV vaccination data collection, including vaccination timing, to better understand the underlying mechanisms and plan for interventions to prevent HPV-related cancers among these populations.

HPV self-collection for cervical cancer screening among survivors of sexual trauma: a qualitative study.

Intimate partner violence affects 20-30% of women in the United States. Disparities in routine cervical cancer surveillance have been demonstrated in certain populations, including victims of intimate partner violence (IPV). This study examined and assessed the acceptability of high-risk HPV (hrHPV) self-collection among individuals who have experienced IPV. We conducted an observational study using qualitative data collection and analysis. We interviewed individuals with a history of IPV and who currently reside in Oregon. This study identified key themes describing knowledge and attitudes towards cervical cancer screening for individuals who have experienced IPV. They include: guideline knowledge, prior office-based cervical cancer screening experience, barriers to cervical cancer screening, at-home hrHPV self-collection experience, and testing confidence. Participants experienced fewer barriers and expressed increased comfort and control with hrHPV self-collection process. Individuals with a history of IPV have lower rates of cervical cancer screening adherence and higher rates of cervical dysplasia and cancer than other populations. The patient-centered approach of hrHPV self-collection for cervical cancer screening can reduce barriers related to the pelvic exam and empower patients to reduce their risks of developing cervical cancer by enabling greater control of the testing process.

Analysis of Expression and Regulation of AKR1C2 in HPV-Positive and -Negative Oropharyngeal Squamous Cell Carcinoma.

Head and Neck Squamous Cell Carcinoma (HNSCC), particularly Oropharyngeal Squamous Cell Carcinoma (OPSCC), is a major global health challenge due to its increasing incidence and high mortality rate. This study investigates the role of aldo-keto reductase 1C2 (AKR1C2) in OPSCC, focusing on its expression, correlation with Human Papillomavirus (HPV) status, oxidative stress status, and clinical outcomes, with an emphasis on sex-specific differences. We analyzed AKR1C2 expression using immunohistochemistry in formalin-fixed, paraffin-embedded tissue samples from 51 OPSCC patients. Additionally, we performed RT-qPCR in cultured HPV16-E6*I and HPV16-E6 overexpressing HEK293 cell lines (p53WT). Statistical analyses were performed to assess the correlation between AKR1C2 expression and patient data. Our results indicate a significant association between increased AKR1C2 expression and higher AJCC classification (p = 0.009) as well as positive HPV status (p = 0.008). Prognostic implications of AKR1C2 varied by sex, whereby female patients with high AKR1C2 expression had better overall survival, whereas male patients exhibited poorer outcomes. Additionally, AKR1C2 expression was linked to HPV status, suggesting a potential HPV-specific regulatory mechanism. These findings underscore the complex interplay among AKR1C2, HPV, and patient sex, highlighting the need for personalized treatment strategies for OPSCC. Targeted inhibition of AKR1C2, considering sex-specific differences, may enhance therapeutic outcomes. Future research should investigate these mechanisms to enhance treatment efficacy.

Subgroup Analysis of TLR2, -3, -4 and -8 in Relation to the Severity of Clinical Manifestations of Cervical HPV Infection.

We present the findings of assessing the expression levels of extracellular TLR2 and TLR4 and intracellular TLR3 and TLR8 correlating with the severity of clinical manifestations of HPV infection. A total of 199 women took part in a single-center prospective comparative research study on TLR2, TLR3, TLR4 and TLR8 expression in HPV-related cervical lesions. TLRs' mRNA expression was analyzed using real-time reverse transcription polymerase chain reaction (RT-PCR). Our results indicate the potential significance of TLR3, TLR4 and TLR8 in responding to HPV infection and its progression to SILs and CC, highlighting the importance of HPV polyinfection in relation to TLR4 and TLR8.