Unveiling the role of HACE1 in cervical cancer: implications for human papillomavirus infection and prognosis.

Background: Cervical cancer, one of the prevalent malignancies among females, is closely associated with human papillomavirus (HPV) infection. Homologous to the E6-AP carboxyl terminus (HECT) domain and ankyrin repeat containing E3 ubiquitin-protein ligase 1 (HACE1) plays pivotal roles in various cancers. This study aimed to elucidate the expression of HACE1 in cervical cancer and its correlation with clinical features. Methods: From The Cancer Genome Atlas Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (TCGA-CESC) and Gene Expression Omnibus (GEO, GSE6791) datasets, we obtained RNA-Seq profiles and associated clinical information. Differential gene analysis was conducted using the R "limma" package. Implications for HPV infection and the overall survival (OS) of cervical cancer were determined by performing differential expression analysis and the Cox proportional hazards regression model. Immunohistochemical analyses were used to validate the expression in cervical cancer and normal cervical tissue. Further, nomogram was constructed to predict OS in cervical cancer. Whether the model was credible was evaluated according to receiver operating characteristic (ROC) curves and concordance curves. To further evaluate the potential functions of HACE1, we conducted functional enrichment analysis. Finally, we assessed methylation levels in HPV+ and HPV- patients in the TCGA-CESC dataset. Results: Utilizing TCGA and GSE6791 datasets, we observed significant upregulation of HACE1 in cervical cancer patients, particularly linked to HPV infection. Immunohistochemical staining revealed enhanced HACE1 expression in tumor tissues. Further analysis demonstrated a significant positive correlation between elevated HACE1 and HPV-associated proteins (E1, E6, and E7). Moreover, high HACE1 expression was associated with adverse prognosis in cervical cancer patients. Multivariate Cox analysis indicated that HACE1 could serve as an independent prognostic factor. We developed a prognostic model integrating HPV subtypes, the International Federation of Gynecology and Obstetrics (FIGO) staging, and HACE1, exhibiting strong predictive efficacy for cervical cancer prognosis. Gene enrichment analysis indicated HACE1's potential involvement in multiple signaling pathways during cervical cancer progression, while the demethylation of cg03002526 in HPV-positive patients might contribute to HACE1 upregulation. Conclusions: Our study reveals that HACE1 upregulation is associated with cervical cancer, particularly in HPV-positive patients. HACE1 emerges as an independent prognostic factor, linked to unfavorable outcomes.

HPV DNA Testing and Mobile Colposcopy for Cervical Precancer Screening in HIV Positive Women: A Comparison Between Two Settings in Ghana and Recommendation for Screening.

INTRODUCTION: Women living with HIV (WLHIV) have higher prevalence and persistence rates of high-risk human papillomavirus (hr-HPV) infection with a six-fold increased risk of cervical cancer. Thus, more frequent screening is recommended for WLHIV. OBJECTIVES: This retrospective descriptive cross-sectional study was conducted to investigate and compare the prevalence of hr-HPV infection and abnormal findings on mobile colposcopy in two cohorts of WLHIV following cervical screening in rural and urban settings in Ghana. METHODS: Through the mPharma 10 000 Women Initiative, WLHIV were screened via concurrent hr-HPV DNA testing (MA-6000; Sansure Biotech Inc., Hunan, China) and visual inspection (Enhanced Visual Assessment [EVA] mobile colposcope; MobileODT, Tel Aviv, Israel) by trained nurses. The women were screened while undergoing routine outpatient reviews at HIV clinics held at the Catholic Hospital, Battor (rural setting) and Tema General Hospital (urban setting), both in Ghana. RESULTS: Two-hundred and fifty-eight WLHIV were included in the analysis (rural, n = 132; urban, n = 126). The two groups were comparable in terms of age, time since HIV diagnosis, and duration of treatment for HIV. The hr-HPV prevalence rates were 53.7% (95% CI, 45.3-62.3) and 48.4% (95% CI, 39.7-57.1) among WLHIV screened in the rural vs urban settings (p-value = .388). Abnormal colposcopy findings were found in 8.5% (95% CI, 5.1-11.9) of the WLHIV, with no significant difference in detection rates between the two settings (p-value = .221). Three (13.6%) of 22 women who showed abnormal colposcopic findings underwent loop electrosurgical excision procedure (LEEP), leaving 19/22 women from both rural and urban areas with pending treatment/follow-up results, which demonstrates the difficulty faced in reaching early diagnosis and treatment, regardless of their area of residence. Histopathology following LEEP revealed CIN III in 2 WLHIV (urban setting, both hr-HPV negative) and CIN I in 1 woman in the rural setting (hr-HPV positive). CONCLUSIONS: There is a high prevalence of hr-HPV among WLHIV in both rural and urban settings in this study in Ghana. Concurrent HPV DNA testing with a visual inspection method (colposcopy/VIA) reduces loss to follow-up compared to performing HPV DNA testing as a standalone test and recalling hr-HPV positive women for follow up with a visual inspection method. Concurrent HPV DNA testing and a visual inspection method may also pick up precancerous cervical lesions that are hr-HPV negative and may be missed if HPV DNA testing is performed alone.

Prevalence of high-risk human papillomavirus infection among women with diabetes mellitus in Accra, Ghana.

BACKGROUND: There is increasing evidence of a higher risk and poorer prognosis of cervical cancer among women with diabetes mellitus (DM) compared to the general population. These are mediated by higher susceptibility to persistent high-risk human papillomavirus (hr-HPV) infection due to dysfunctional clearance in an immunocompromised state. We aimed to determine the prevalence of hr-HPV infection and cervical lesions in a cohort of women with DM in Ghana. We further disaggregated the prevalence according to DM type and explored factors associated with hr-HPV infection. METHODS: This retrospective descriptive cross-sectional study assessed 198 women with DM who underwent cervical screening via concurrent hr-HPV DNA testing and visual inspection with acetic acid in an outpatient department of the National Diabetes Management and Research Centre in Korle-Bu Teaching Hospital, Accra from March to May 2022. Univariate and multivariable binary logistic regression were used to explore factors associated with hr-HPV positivity. RESULTS: Among 198 women with DM (mean age, 60.2 ± 12.1 years), the overall hr-HPV prevalence rate was 21.7% (95% CI, 16.1-28.1), disaggregated as 1.5% (95% CI, 0.3-4.4) each for HPV16 and HPV18 and 20.7% (95% CI, 15.3-27.0) for other HPV genotype(s). Respective hr-HPV prevalence rates were 37.5% (95% CI, 15.2-64.6) for type 1 DM, 19.8% (95% CI, 13.9-26.7) for type 2 DM, and 25.0% (95% CI, 8.7-49.1) for unspecified/other DM types. Past use of the combined contraceptive pill independently increased the risk of hr-HPV infection by approximately three times (adjusted odds ratio [aOR] = 2.98; 95% CI, 1.03 - 8.64; p-value = 0.045), whereas each unit increase in FBG level increased the odds of hr-HPV infection by about 15% (aOR = 1.15; 95% CI, 1.02 - 1.30; p-value = 0.021). CONCLUSION: Our study points to a high prevalence of hr-HPV among women with DM and highlights a need for glycemic control among them as this could contribute to lowering their odds of hr-HPV infection. The low overall rates of HPV vaccination and prior screening also indicate a need to build capacity and expand the scope of education and services offered to women with DM as regards cervical precancer screening.

DNA methylation as a triage tool for cervical cancer screening - A meeting report.

Introduction: DNA methylation is proposed as a novel biomarker able to monitor molecular events in human papillomavirus (HPV) infection pathophysiology, enabling the distinction between HPV-induced lesions with regression potential from those that may progress to HPV-related cancer. Methods: This meeting report summarises the presentations and expert discussions during the HPV Prevention and Control Board-focused topic technical meeting on DNA methylation validation in clinician-collected and self-collected samples, novel DNA methylation markers discovery, implementation in cervical cancer screening programs, and their potential in women living with human immunodeficiency virus (HIV). Results: Data presented in the meeting showed that HPV-positive, baseline methylation-negative women have a lower cumulative cervical cancer incidence than baseline cytology-negative women, making DNA methylation an attractive triage strategy. However, additional standardised data in different settings (low- versus high-income settings), samples (clinician-collected and self-collected), study designs (prospective, modelling, impact) and populations (immunocompetent women, women living with HIV) are needed. Conclusion: Establishing international validation guidelines were identified as the way forward towards accurate validation and subsequent implementation in current screening programs.

Awareness, knowledge and attitudes of human papillomavirus infection, screening and vaccination: a survey study in Greece.

PURPOSE: To evaluate the awareness and existing knowledge of a portion of the Greek population about prevention, screening, and HPV vaccination. METHODS: A questionnaire designed in Google forms has been distributed through social media between June 2021 and December 2021 in men and women aged > 16 years old. Statistical analysis was performed using the SPSS 20.0 program. Inferential analysis was performed to evaluate differences in responses among men and women. RESULTS: We enrolled 2685 participants. Of those, 2285 were women, 386 were men, while 14 respondents chose not to respond to this question. Various age groups were detected with those aged between 26 and 30 years old being the predominant one. Participants with a higher education constituted 36.5% of the population. Most respondents were married (59.8%). In socioeconomic terms 75.5% of participants were employed whereas, monthly income ranged between 1000 and 1500 euros in the predominant group (36.8%). Only 40% of females and 3.9% of males were vaccinated against HPV. Adolescent immunization, acceptability rates reached 92.7% among female and 82.1% among male responders. Although, only a small proportion of the participants were not aware of the existence of HPV, 24.1% of males and 23.4% of females had the impression that condom use may provide absolute immunity to HPV and only 51.6% of males and 60.4% of females were aware about the high prevalence of HPV in the general population. Logistic regression analysis indicated that male participants as well as those aged > 50 years and those choosing to reject vaccination had decreased knowledge of the basic pathophysiology of HPV infection, as well as knowledge related to the existence and use of HPV DNA as a screening tool and the existence and efficacy of HPV vaccination. CONCLUSION: Our results indicate that although awareness of the existence of HPV infection is high in Greek general population, the actual perception of the pathophysiology of transmission and importance of HPV testing and vaccination is low. Targeting specific population groups is essential to help increase HPV coverage and screening.

Effect of the human papillomavirus vaccine on the risk of genital warts: a nationwide cohort study of Korean adolescent girls.

OBJECTIVES: The purpose of this study was to assess the effectiveness of human papillomavirus (HPV) vaccination administered to adolescent girls through Korea's National Immunization Program. METHODS: This retrospective cohort study included patients who were 12-13 years old, whether vaccinated or unvaccinated, between July 2016 and December 2017. The incidence of genital warts (GWs) was monitored through 2021. Time-stratified hazard ratios (HRs) were estimated, adjusting for birth year, socioeconomic status, and the level of urbanization of the region, and were presented with 95% confidence intervals (CIs). Data were sourced from the Immunization Registry Integration System, linked with the National Health Information Database. RESULTS: The study included 332,062 adolescent girls, with an average follow-up period of approximately 4.6 years. Except for the first year, the HRs for the vaccinated group were lower than those for the unvaccinated group. The HRs for specific cut-off years were as follows: year 2, 0.62 (95% CI, 0.31 to 1.13); year 3, 0.58 (95% CI, 0.35 to 0.96); and year 4 and beyond, 0.39 (95% CI, 0.28 to 0.52). CONCLUSIONS: Our findings indicate that HPV vaccination was associated with a reduction in the risk of GWs among adolescent girls. Notably, this reduction became significant as the incidence of GWs increased with age.

Effectiveness of trichloroacetic acid versus electrocautery for the treatment of anal high-grade squamous intraepithelial lesions in persons with HIV.

PURPOSE: This study aimed to compare trichloroacetic acid (TCA) versus electrocautery (ECA) for the treatment of anal high-grade squamous intraepithelial lesions (HSIL). METHODS: This is an observational, single-center study. All subjects with HIV who had anal HSIL treated with TCA or ECA from 2010 to 2022 were included. Effectiveness was evaluated by on-treatment analysis, defining response as the resolution of HSIL and recurrence as a new diagnosis of HSILs during follow-up. A propensity score analysis was used to adjust for confounding factors. RESULTS: In total, 227 and 260 HSIL episodes were treated with ECA and TCA, respectively. Response was observed in 61.7% (95% CI: 55.3-68) of cases treated with ECA and in 73.1% (95% CI: 67.8-78.5) with TCA (p = .004). The effectiveness of TCA was higher in large and multifocal HSILs. Side effects were common with both treatments, but no serious events were described. Tolerability was good in 77.1% and 80.7% of patients treated with ECA and TCA, respectively. At 24 months, recurrent HSIL were observed in 36.3% (95% CI: 27.3-45) and 28% (95% CI: 20.2-35.8) in the ECA and TCA groups (p = .049). A nadir CD4 cell count ≤200 cells/µl was found to be a risk factor for recurrence (OR: 1.77; 95% CI: 1.12-2.78). CONCLUSIONS: In this study, treatment with TCA showed high effectiveness, low recurrence and good tolerability. Considering the benefits of TCA, it could be considered one of the first-line treatments for anal HSIL.

Monogenic etiologies of persistent human papillomavirus infections: A comprehensive systematic review.

PURPOSE: Persistent human papillomavirus infection (PHPVI) causes cutaneous, anogenital, and mucosal warts. Cutaneous warts include common warts, Treeman syndrome, and epidermodysplasia verruciformis, among others. Although more reports of monogenic predisposition to PHPVI have been published with the development of genomic technologies, genetic testing is rarely incorporated into clinical assessments. To encourage broader molecular testing, we compiled a list of the various monogenic etiologies of PHPVI. METHODS: We conducted a systematic literature review to determine the genetic, immunological, and clinical characteristics of patients with PHPVI. RESULTS: The inclusion criteria were met by 261 of 40,687 articles. In 842 patients, 83 PHPVI-associated genes were identified, including 42, 6, and 35 genes with strong, moderate, and weak evidence for causality, respectively. Autosomal recessive inheritance predominated (69%). PHPVI onset age was 10.8 ± 8.6 years, with an interquartile range of 5 to 14 years. GATA2,IL2RG,DOCK8, CXCR4, TMC6, TMC8, and CIB1 are the most frequently reported PHPVI-associated genes with strong causality. Most genes (74 out of 83) belong to a catalog of 485 inborn errors of immunity-related genes, and 40 genes (54%) are represented in the nonsyndromic and syndromic combined immunodeficiency categories. CONCLUSION: PHPVI has at least 83 monogenic etiologies and a genetic diagnosis is essential for effective management.

Prevalencia y factores de riesgo de la neoplasia intraepitelial anal en pacientes con lesión intraepitelial cervical de alto grado / Prevalence and risk factors for anal intraepithelial neoplasia in patients with high- grade cervical intraepithelial lesion

Resumen OBJETIVO: Determinar la prevalencia de alteraciones en la citología anal, infección anal por virus del papiloma humano y en la neoplasia intraepitelial anal; además, explorar los factores de riesgo y los serotipos asociados en pacientes con lesión intraepitelial cervical de alto grado, a partir de la hipótesis de que esta población tiene mayor riesgo de lesiones precursoras o cáncer anal. MATERIALES Y MÉTODOS: Estudio observacional, descriptivo y transversal, con componente analítico, efectuado en pacientes con diagnóstico de lesión intraepitelial cervical de alto grado (LIEAG) en dos instituciones de salud: una privada y otra pública de Bogotá, atendidas entre enero de 2017 y febrero de 2018. Se efectuó un muestreo no probabilístico, por conveniencia. RESULTADOS: Se incluyeron 119 participantes, en 4 de ellas se evidenció, en la citología anal, el hallazgo de células anormales en el tejido que reviste la parte exterior del cuello uterino. Se encontraron 14 anoscopias anormales que dieron una prevalencia de neoplasia intraepitelial anal del 6.7%. Siete eran neoplasia intraepitelial anal de bajo grado y una de alto grado. Se encontró infección por VPH anal en 45 participantes (37.8%) y se detectaron genotipos de VPH-AR en 29 participantes (24.4%). Más de 3 compañeros sexuales, más de 3 hijos y tener menos de 21 años antes del primer embarazo tuvieron un valor de p < 0.05 que confiere mayor riesgo de infección por VPH anal. CONCLUSIÓN: Es importante establecer en Colombia protocolos para la detección de la neoplasia intraepitelial anal en grupos de alto riesgo, como las pacientes con neoplasia intraepitelial cervical o cáncer de cuello uterino, e incentivar el adiestramiento en la anoscopia de alta resolución en especialistas relacionados con el diagnóstico de patología anogenital.

Abstract OBJECTIVE: To determine the prevalence of alterations in anal cytology, anal human papillomavirus infection, and anal intraepithelial neoplasia, and to explore the risk factors and associated serotypes in patients with high-grade cervical intraepithelial lesion, based on the hypothesis that this population is at higher risk for precancerous lesions or anal cancer. MATERIALS AND METHODS: Observational, descriptive, cross-sectional study, with analytical component, performed in patients diagnosed with high-grade cervical intraepithelial lesion (HG-CIL) in two health institutions: one private and one public in Bogota, visited between January 2017 and February 2018. A non-probabilistic sampling was performed, by convenience, with a sample calculated in 124 patients. RESULTS: 119 participants were included, in 4 of them it was evidenced in the anal cytology, the finding of abnormal cells in the tissue lining the outside of the cervix. Fourteen abnormal anoscopies were found, giving a prevalence of anal intraepithelial neoplasia of 6.7%. Seven were low-grade anal intraepithelial neoplasia and one was high-grade. Anal HPV infection was detected in 45 participants (37.8%) and HR-HPV genotypes were detected in 29 participants (24.4%). More than 3 sexual partners, more than 3 children and being younger than 21 years before first pregnancy had a p-value < 0.05 conferring an increased risk of anal HPV infection. CONCLUSION: It is important to establish protocols in Colombia for the detection of anal intraepithelial neoplasia in high-risk groups, such as patients with cervical intraepithelial neoplasia or cervical cancer, and to promote training in high-resolution anoscopy in specialties related to the diagnosis of anogenital pathology.

Efficacy of Human Papillomavirus Vaccines for Recalcitrant Anogenital and Oral Warts.

Human papillomavirus (HPV) vaccines are preventive measures to decrease HPV infection rates. Knowledge of their efficacy as treatment options for anogenital warts (AGWs) and oral warts (OWs) is limited. To evaluate the efficacy of HPV vaccinations in recalcitrant AGWs and OWs (lesions persisting more than 6 months despite conventional treatments), we compared a group of patients treated with standard therapies plus an HPV vaccine with a group of patients treated with standard therapies only. The response to treatment (in terms of the number of lesions) in the two groups was compared. Data were analyzed with the χ2 test and p values < 0.05 were considered to be statistically significant. The study included 14 patients (group A = cases) who received 3 doses of an intramuscular HPV vaccine (Gardasil 4 or Gardasil 9) in addition to the standard treatments for AGWs and OWs, and 15 age- and sex-matched patients (group B = controls) with an analogous number of lesions to group A who received only standard therapies. After 12 months, 85% of patients of group A versus 33% of group B had positive clinical outcomes (0.004). Our findings suggest a possible therapeutic role of HPV vaccines in addition to standard treatments for AGWs/OWs. Preventive vaccines, blocking the viral entry through the induction of L1-specific antibodies, can prevent autologous reinfections (through auto-inoculation) and favor the elimination of the virus.

p16 Overexpression in Sinonasal Squamous Cell Carcinoma: Association with Human Papillomavirus and Prediction of Survival Outcomes.

p16 overexpression is often used as a surrogate marker for human papillomavirus (HPV) infection in oropharyngeal squamous cell carcinoma but remains an uncertain diagnostic tool for HPV-related sinonasal squamous cell carcinoma (SNSCC). Our study involved 79 consecutive SNSCC patients who were treated at a tertiary referral university hospital during 2006-2021. We retrospectively examined their clinical characteristics and conducted p16 immunohistochemistry and HPV detection. We found that 12.7% of the patients exhibited p16 overexpression, which was significantly more common in the nasal cavity and increased from 2015 onward. The HPV was a high-risk type and viral loads ranged from 4.2 to 1.6 × 106 copies/ng DNA with genome integration. Five-year overall survival (OS) and five-year relapse-free survival (RFS) rates were 74.6% and 69.9%, respectively. Our multivariate analysis showed that T category (T1-4a) and hemoglobin levels (≥13.7) were significant favorable prognostic factors for OS, while T category, performance status, and p16 overexpression were significantly associated with RFS. In patients with p16 overexpression, OS was 100% and RFS was 90%. Our findings suggest that p16 overexpression is a reliable surrogate marker for transcriptionally active HPV infection and predicts a favorable prognosis.

Impact of cervical intraepithelial neoplasia and treatment on IVF/ICSI outcomes.

STUDY QUESTION: Does treatment selection for cervical lesions affect the outcome of IVF/ICSI? SUMMARY ANSWER: There was no difference in pregnancy outcome between treated and untreated groups, or between different types of IVF/ICSI treatment. WHAT IS KNOWN ALREADY: Human papillomavirus (HPV) infection and HPV-induced cervical lesions are associated with decreased fertility, and cervical intraepithelial neoplasia (CIN) treatment may increase the risk of adverse pregnancy outcomes. STUDY DESIGN, SIZE, DURATION: Between 2018 and 2020, 190 women with infertility who had abnormal HPV screening or cytology results prior to IVF/ICSI, and were diagnosed with CIN2/CIN3 by colposcopy biopsy at a tertiary hospital, were enrolled in a retrospective cohort study with follow-up until 31 December 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients with infertility who were diagnosed with CIN2/CIN3 by colposcopy biopsy were divided into the treatment and expectant management groups. The treatment group was divided into two intervention subgroups: the ablative therapy group and the surgical treatment group. The baseline data, number of oocytes retrieved, and rates of fertilization, high-quality embryos, positive serum HCG, clinical pregnancy, abortion, live birth, and cumulative pregnancy were compared among groups. MAIN RESULTS AND THE ROLE OF CHANCE: Among the 190 patients included in the study, 152 were diagnosed with CIN2, and 38 patients had CIN3. There was no significant difference in the baseline data between the treatment and expectant groups. The time from confirmed lesions to the onset of gonadotrophin administration in the surgical treatment group was significantly longer than in the ablative therapy group and the expectant group (P = 0.007 and P = 0.024, respectively). For the treatment and expectant groups, respectively, the average number of oocytes retrieved (12.95 ± 8.77; 13.32 ± 9.16), fertilization rate (71.01 ± 23.86; 64.84 ± 26.24), and high-quality embryo rate (48.93 ± 30.72; 55.17 ± 34.13) did not differ, and no differences were detected between the different treatment subgroups. There were no differences among groups in rates of HCG positivity, clinical pregnancy, miscarriage, live birth, or cumulative pregnancy. The live birth rate in the surgical treatment group was slightly higher than that in the expectant groups (77.78% versus 66.67%), but the difference was not statistically significant. The 3-year cumulative pregnancy rates in the surgical treatment and expectant groups were 58.19% and 64.00%, respectively. LIMITATIONS, REASONS FOR CAUTION: This is a retrospective study, which by nature can include selection bias, and the number of cases in the expectant group was <30, which may result in a false-negative result owing to the small sample size. WIDER IMPLICATIONS OF THE FINDINGS: For patients with CIN2/CIN3, the treatment of cervical lesions does not affect the outcome of IVF/ICSI. Patients with CIN2 can enroll for IVF/ICSI cycles, with close follow-up to prevent the progression of cervical lesions, in order to avoid further delay in starting ART. For patients with CIN3, ovulation induction and embryo cryopreservation can be initiated as soon as possible after cervical lesions are treated, and frozen-thawed embryo transfer can be carried out 9-12 months later. STUDY FUNDING/COMPETING INTEREST(S): This work was funded by the Key Clinical Projects of the Peking University Third Hospital (to Y.W., BYSYZD2021014). The authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

The Effects of Human Papillomavirus Status and Treatment on the Positive Predictive Value of Post-radiotherapy 18F-Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography in Advanced Head and Neck Squamous Cell Carcinoma.

AIMS: The high negative predictive value of post-chemoradiation (CRT) positron emission tomography-computed tomography (PET-CT) is well established in head and neck squamous cell cancers (HNSCC). The positive predictive value (PPV) remains under scrutiny, with increasing evidence that it is affected by several factors. The aim of this study was to assess the PPV of post-treatment PET-CT for residual nodal disease when stratified by treatment modality and tumour human papillomavirus (HPV) status. MATERIALS AND METHODS: This was a retrospective cohort study in a tertiary oncology centre carried out between January 2013 and December 2019. Patients were radically treated with radiotherapy only/CRT for node-positive HNSCC. PET-CT nodal responses were categorised as complete, equivocal (EQR) or incomplete (ICR), and outcomes extracted from electronic records. RESULTS: In total, 480 patients were evaluated, all had a minimum potential follow-up of 2 years, with a median of 39.2 months. The PPV of 12-week PET-CT was significantly different between HPV-positive (22.5%) and HPV-unrelated (52.7%) disease, P < 0.001. It was also significantly different between the CRT (24.8%) and radiotherapy-only (51.1%) groups, P = 0.001. The PPV of an EQR was significantly less than an ICR, irrespective of HPV status and primary treatment modality. In HPV-positive disease, the PPV of an EQR was 9.0% for the CRT group compared with 21.4% for radiotherapy only, P = 0.278. The PPV in those who achieved an ICR was 34.2% in the CRT group, significantly lower than 70.0% in the radiotherapy-only group, P = 0.03. CONCLUSION: The PPV of 12-week PET-CT is significantly lower for HPV-positive compared with HPV-unrelated HNSCC. It is poorer in patients with HPV-positive disease treated with CRT compared with radiotherapy alone.

Prevalence and Risk Factors for High-Risk Human Papillomavirus Infection and Cervical Disorders: Baseline Findings From an Human Papillomavirus Cohort Study.

BACKGROUND: A persistent infection by high-risk human papillomavirus (HR-HPV) is a prerequisite for the development of cervical neoplasms; however, most studies have focused on risk factors associated with HPV-16 and HPV-18 only. OBJECTIVES: We assessed the association of risk factors with the prevalence of HPV-16, HPV-18, and non-16/18 HR-HPV infection and with the occurrence of cervical lesions in the baseline of a cohort study of HPV persistence in a Mexican population. METHODS: Cross-sectional study within the baseline of a 5-year dynamic cohort study of HR-HPV persistence in women with an abnormal cytology study result from 2015 to 2021. HPV DNA was detected using the Anyplex II HPV 28 kit. Data on lifestyle, sociodemographic, and reproductive factors were assessed using bivariate and multivariate analyses to determine the association of risk factors with HR-HPV infection status and histopathologic diagnosis. RESULTS: A total of 373 women were included in the study. The overall prevalence of HR-HPV infection was 69.97%. The most prevalent HR-HPV genotypes, including single and multiple infections, were HPV-53 (13.4%), HPV-16 (11.8%), HPV-58 (10.9%), HPV-31 (10.9%), and HPV-66 (10.7%). We found 90 multiple HR-HPV infection patterns, all of them with α-6 and -9 species. Significant associations of multiple HPV-16 and non-16/18 HR-HPV infections were found with marital status, number of lifetime sexual partners, and smoking history. The most prevalent genotype in CIN1 and CIN2 patients was HPV-16. No association was found between biological plausibility risk factors and cervical lesions. CONCLUSIONS: The risk factors for non-16/18 HR-HPV multiple infections are no different than those linked to HPV-16 multiple infections.

Association of Nasopharynx Cancer with Human Papillomavirus Infections.

This population-based study aims to examine the association between nasopharyngeal carcinoma and human papillomavirus infections. This study included 2747 individuals aged 20 years and older who were diagnosed with nasopharynx cancer as cases and 13,735 propensity-score-matching controls. Multivariate logistic regression models were employed to quantitatively assess the association of nasopharynx cancer with human papillomavirus infections while considering age, sex, monthly income, geographic location, and urbanization level of the patient's residence as well as diabetes, hypertension, and hyperlipidemia. Our chi-squared test indicated a significant dissimilarity in previous human papillomavirus infection rates between nasopharynx cancer patients and controls (12.7% vs. 7.2%, p < 0.001). The adjusted odds ratio (OR) for prior human papillomavirus infections was found to be significantly higher for nasopharyngeal carcinoma cases compared to controls at a value of 1.869 with confidence interval ranging from 1.640 to 2.128. Among female participants, compared to controls, the adjusted OR of prior human papillomavirus infections was 2.150 (95% CI = 1.763-2.626) in patients with nasopharynx cancer. In male participants sampled in this study, we observed a statistically significant association between prior human papillomavirus infections and nasopharynx cancer (adjusted OR = 1.689; 95% CI = 1.421-2.008). Our study indicates a noteworthy association between previous human papillomavirus infections and nasopharyngeal carcinoma.

Cervical precancer screening with HPV DNA testing and mobile colposcopy in women with sickle cell disease in Accra, Ghana.

Background: Worldwide, about 20-25 million people are affected by sickle cell disease (SCD), with 60% of patients living in sub-Saharan Africa. Despite recent therapeutic advancements resulting in improved life expectancy among SCD patients, the prevalence of high-risk human papillomavirus (hr-HPV) and cervical lesions have not been studied in women with SCD. We determined the prevalence of hr-HPV and cervical lesions among women with SCD and recommended strategies for reducing cervical cancer incidence in this cohort. Methods: Through the mPharma 10,000 Women Initiative, women with SCD attending routine visits at the Ghana Institute of Clinical Genetics SCD clinic were screened by trained nurses. Screening was performed via concurrent MA-6000 hr-HPV DNA testing and enhanced visual assessment (EVA) mobile colposcopy from mobileODT. Results: Among 168 participants screened (mean age, 43.0 years), the overall prevalence rates of hr-HPV infection and cervical lesions were 28.6% (95% CI, 21.7-35.4) and 3.6% (95% CI, 0.8-6.4), respectively. The hr-HPV prevalence rates stratified by haemoglobin genotype were 29.4% (95% CI, 19.7-39.1) and 28.6% (95% CI, 18.5-38.7) for genotypes SS and SC, respectively. None of the five women with the SF genotype tested hr-HPV positive, and the only patient with Sbthal genotype tested hr-HPV positive. Two women were EVA 'positive' but hr-HPV negative, whereas four were EVA positive and hr-HPV positive. Exploratory analysis revealed no significant associations between hr-HPV positivity and age, education level, marital status or parity. Conclusion: In the absence of a comprehensive national cervical screening programme aimed at including women with SCD as a special population, cervical cancer may increase in frequency among SCD patients. Thus, there is a need to build capacity and expand the scope of screening services for women with SCD.

Comparative Efficacy and Safety of Chinese Patent Medicines for Cervical High-risk Human Papillomavirus Infection: A Bayesian Network Meta-analysis.

Background: Many Chinese patent medicines have been reported to show anti-tumor cell effects on cervical cancer. To estimate the comparative effectiveness and safety of Chinese patent medicines for cervical high-risk human papillomavirus (HR-HPV) infection. Methods: Randomized controlled trials (RCTs) of Chinese patent medicines for HR-HPV infection were searched in eight databases until 31 August 2022, and two review authors independently extracted data and assessed the risk of bias. Outcomes concerning efficacy were evaluated as odds ratio (OR) and 95% credible intervals (CrI) utilizing R 4.1.2 and Stata 16.1. The protocol was registered on the International Prospective Register of Systematic Reviews (CRD42022351120). Results: We ultimately identified 60 RCTs that involved 5,951 participants and 8 interventions. Chinese patent medicines combined with recombinant human interferon (rhIFN) have better treatment effects than rhIFN alone. The results showed that Baofukang suppository (BFK) combined with rhIFN is greater for the rate of HR-HPV clearance follow-up at 6 months (SUCRA = 78.16%). Kushen gel (KS) combined with rhIFN ranked first for the rate of HR-HPV clearance after treatment (SUCRA = 90.77%). Furthermore, KS + rhIFN is most likely to be the best intervention for improving the clinical effectiveness rate (SUCRA = 87.39%). Adverse reactions were not statistically significant in BFK + rhIFN versus BFK, BFK + rhIFN versus rhIFN, and BFK versus rhIFN. Conclusion: The combination of Chinese patent medicines with rhIFN may demonstrate a higher efficacy than rhIFN alone in clearing the virus and improving cervical symptoms. Weighing with the clinical comprehensive efficacy, BFK + rhIFN and KS + rhIFN maybe the optimal treatments for cervical HR-HPV infection. However, more high-quality randomized controlled trials are needed in the future to further confirm the efficacy and safety of proprietary Chinese medicines for cervical HR-HPV infection.

[HPV-associated pathology of the oral mucosa and anogenital area. (Rationale for combined therapy)]. / VPCh-assotsiirovannaya patologiya slizistoi obolochki rta i anogenital'noi oblasti. (Opyt primeneniya kombinirovannoi terapii).

THE AIM OF THE STUDY: Was to evaluate the effectiveness and duration without a relapse period in patients with HPV-associated pathology of the oral mucosa and in combination with lesions of the anogenital region during combined therapy, including destruction and Panavir. MATERIALS AND METHODS: The study included 60 women diagnosed with «Viral warts. Genital condyloma of the oral cavity. 15 patients were also diagnosed with «Anogenital warts¼. The patients were divided into three groups of 20 women (15 with HPV-associated pathology of the oral cavity; 5 with combined HPV-associated pathology of the oral cavity and anogenital area). In the first group, the drug Panavir was administered intravenously. Between the third and fourth injections radiosurgical destruction of condylomas was carried out followed by Panavir gel applications until complete epithelialization of the destruction zone and further use of Panavir-inlight spray in the oral cavity and Panavir-intim spray in the anogenital area for 4 weeks. In the second group, the destruction of genital warts was carried out only with local treatment identical to that in the first group. In the third group after destruction applications of an oil solution of vitamin A were added to the oral mucosa 3-4 times a day until complete epithelization of the lesion, an alcohol solution of fucorcin and panthenol cream were applied externally in the anogenital area. RESULTS: According to clinical and laboratory monitoring after 3, 6 and 12 months, HPV elimination in the first group was achieved in 70, 85 and 90% of cases; in the second group in 50, 75 and 80%; in the third group in 30, 40 and 40%, respectively; within 12 months, relapses in the first group were registered in 10% of cases; in the second and third groups in 20% and 45% of cases, respectively. CONCLUSION: Combined therapy including destruction and complex use of different dosage forms of the drug Panavir showed higher clinical efficacy and allowed to achieve a reduction in the rate of condyloma relapses.

Transcriptional analysis reveals distinct gene expression profiles of three bowenoid papulosis patients.

Bowenoid papulosis (BP) is a benign and possibly carcinogenic disease associated with human papillomavirus (HPV) infection, which has been increasingly recognised and paid attention to in recent years, but the potential mechanisms still remain unclear. In our study, three patients who were diagnosed with BP were enrolled into our research. Skin biopsies were taken and were separated into two parts, one part was for HE staining and the others were for RNA-sequencing (RNA-seq). All the three patents were human papillomavirus (HPV) positive and HE staining revealed typical skin histopathological changes in BP, including dyskeratosis, hyperplasia and hypertrophy of the granular and spinous layers, atypical keratinocytes. RNA-seq analysis demonstrated that a total of 486 differentially expressed genes (DEGs) were detected between the skin tissues from BP and the controls, among which, 320 genes were significantly upregulated and 166 genes were dramatically downregulated. GO enrichment revealed that antigen binding, cell cycle, immune response and keratinisation to be the most notably altered pathways, whereas KEGG analysis indicated that cell cycle cytokine-cytokine receptor interaction, ECM receptor interaction and p53 signalling pathway to be the most significantly changed signalling pathways in BP. Furthermore, metabolism-associated enrichment analysis showed that cholesterol metabolism, metabolism of xenobiotics by cytochrome p450 and pyrimidine metabolism to be the most dramatically dysregulated metabolic pathways in BP as compared to normal controls. Our study revealed that inflammation, metabolism and cell proliferation signalling pathways might be the most important pathways for BP disease, targeted inhibiting of these signals might be a potential method for BP treatment.