Cost-effectiveness of single-visit cervical cancer screening in KwaZulu-Natal, South Africa: a model-based analysis accounting for the HIV epidemic.

Introduction: Women living with human immunodeficiency virus (WLHIV) face elevated risks of human papillomavirus (HPV) acquisition and cervical cancer (CC). Coverage of CC screening and treatment remains low in low-and-middle-income settings, reflecting resource challenges and loss to follow-up with current strategies. We estimated the health and economic impact of alternative scalable CC screening strategies in KwaZulu-Natal, South Africa, a region with high burden of CC and HIV. Methods: We parameterized a dynamic compartmental model of HPV and HIV transmission and CC natural history to KwaZulu-Natal. Over 100 years, we simulated the status quo of a multi-visit screening and treatment strategy with cytology and colposcopy triage (South African standard of care) and six single-visit comparator scenarios with varying: 1) screening strategy (HPV DNA testing alone, with genotyping, or with automated visual evaluation triage, a new high-performance technology), 2) screening frequency (once-per-lifetime for all women, or repeated every 5 years for WLHIV and twice for women without HIV), and 3) loss to follow-up for treatment. Using the Ministry of Health perspective, we estimated costs associated with HPV vaccination, screening, and pre-cancer, CC, and HIV treatment. We quantified CC cases, deaths, and disability-adjusted life-years (DALYs) averted for each scenario. We discounted costs (2022 US dollars) and outcomes at 3% annually and calculated incremental cost-effectiveness ratios (ICERs). Results: We projected 69,294 new CC cases and 43,950 CC-related deaths in the status quo scenario. HPV DNA testing achieved the greatest improvement in health outcomes, averting 9.4% of cases and 9.0% of deaths with one-time screening and 37.1% and 35.1%, respectively, with repeat screening. Compared to the cost of the status quo ($12.79 billion), repeat screening using HPV DNA genotyping had the greatest increase in costs. Repeat screening with HPV DNA testing was the most effective strategy below the willingness to pay threshold (ICER: $3,194/DALY averted). One-time screening with HPV DNA testing was also an efficient strategy (ICER: $1,398/DALY averted). Conclusions: Repeat single-visit screening with HPV DNA testing was the optimal strategy simulated. Single-visit strategies with increased frequency for WLHIV may be cost-effective in KwaZulu-Natal and similar settings with high HIV and HPV prevalence.

Investigating the role of Epstein-Barr virus and human papillomavirus types 16 and 18 co-infections in cervical disease of Iranian women.

Introduction: High-risk human papillomaviruses (HR-HPVs) are known to contribute to cervical cancer (CC), but the role of Epstein-Barr virus (EBV) in this process remains unclear, despite EBV's widespread detection in premalignant and malignant cervical tissues. Methods: In this cross-sectional study of 258 cervical samples, including both formalin-fixed paraffin-embedded (FFPE) and fresh cervical tissues, the presence and viral load of HR-HPVs (HPV-16 and HPV-18) and EBV were evaluated in Iranian women with cervical intraepithelial neoplasia (CIN), squamous cell carcinoma (SCC), and a cervicitis control group using real-time PCR. Results: The study revealed a significant correlation between disease severity and both increased HPV-16 positivity and HPV-16 and HPV-18 co-infection (p<0.001). Interestingly, the control group had a higher frequency of EBV-positive cases than SCC/CIN groups (p<0.001). HPV-16 DNA load increased with disease severity (P<0.001), while HPV-18 showed no significant difference (P=0.058). The control group had a higher EBV DNA load compared to SCC/CIN groups (P=0.033). HPV-16 increased the risk of CIN II, CIN III, and SCC, while HPV-18 increased the risk of CIN II and CIN III. Notably, EBV was associated with a lower risk of CIN groups and SCC. Conclusions: No significant difference in EBV co-infection with HPV-16/18 was found, failing to support the hypothesis that EBV is a cofactor in CC. However, high EBV viral load in the control group suggests a potential "hit and run hypothesis" role in CC progression. This hypothesis suggests that EBV may contribute briefly to the initiation of CC with an initial impact but then becomes less actively involved in its ongoing progression.

The Oncogenic Potential of Human Papillomavirus in Relation to Multiple Types of Cancer in Saudi Arabia: A Systematic Review.

The oncogenic potential of human papillomavirus (HPV) has been widely acknowledged in relation to multiple types of cancer. The objective of this investigation was to conduct a comprehensive assessment of the available evidence pertaining to the correlation between HPV and various types of cancer, such as cervical, colon, ovarian, and head and neck cancers, in the Kingdom of Saudi Arabia (KSA). The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were complied with to conduct a systematic literature search aimed at identifying studies that explore the correlation between HPV and the specified cancers. Databases such as Web of Science, Embase, PubMed, and the Cochrane Library were queried up until May of 2023. Relevant literature was obtained, information was extracted, and the methodological rigor was evaluated. The high-risk HPV, namely HPV-16 and HPV-18, were detected as the most prevalent variants in KSA. A significant proportion of cervical cancer cases in the region were found to be associated HPV infection. The molecular tests have furnished evidence that establishes a connection between HPV infection and colonic polyps as well as colorectal cancer. This finding suggests that HPV may have a plausible role in the etiology of these medical conditions. The results of genotyping and integration analyses suggest a probable correlation between HPV and the development of ovarian cancer. Additionally, the prevalence of head and neck squamous cell cancer related to HPV was notably reduced in this particular geographical area. This study presents persuasive findings that establish a connection between HPV and cervical cancer and proposes plausible correlations with squamous cell carcinomas in the colon, ovaries, and head and neck. The aforementioned results emphasize the necessity for additional inquiry into the function of HPV in the onset and advancement of said malignancies. Further investigations are necessary to augment our comprehension of the role of HPV in these neoplasms.

The prevalence of human papillomavirus in ocular surface squamous neoplasia in HIV positive and negative patients in a South African population.

PURPOSE: To assess the prevalence and subtypes of Human Papillomavirus (HPV) in Ocular Surface Squamous Neoplasia (OSSN) in Human Immunodeficiency Virus (HIV) positive and negative patients in South Africa. BASIC PROCEDURES: This study was a single center retrospective cross-sectional study, conducted at Tygerberg Hospital, Western Cape, South Africa. We assessed 63 histopathologically confirmed OSSN formalin-fixed paraffin-embedded (FFPE) tissue blocks from 2015-2023. The presence of HPV was determined using the Hybrispot Direct Flow Chip Kit. Corresponding clinical data was retrieved from the National Health Laboratory Service (NHLS) central data warehouse. MAIN FINDINGS: Of the confirmed OSSN samples, 66.7% tested positive for HPV (95% confidence interval [CI] 54-77.3%). Of the 42 HPV positive samples, 38 (90.5%) had one or more known genotypes detected and 4 had unknown genotypes. The most prevalent subtypes were HPV 11, 16 and 18 (found in 61.9%, 52.4% and 33.3% of HPV positive samples respectively). 88.9% of the lesions biopsied were from HIV positive patients, of whom 56.4% had a CD4 + count of < 200 cells/µL. A lower median CD4 + count was detected among HIV positive patients with invasive squamous cell carcinoma compared to those with moderate dysplasia (p < 0.0198). CONCLUSIONS: There is a high prevalence of HPV in OSSN in South Africa. Certain subtypes namely, 11, 16, 18, 31, 33 and 35 may be more carcinogenic. HIV with HPV co-infection may be linked as a causative factor in the development of OSSN.

Human papillomavirus infection and the risk of cancer at specific sites other than anogenital tract and oropharyngeal region: an umbrella review.

BACKGROUND: 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. METHODS: 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). FINDINGS: 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. INTERPRETATION: 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. FUNDING: 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.

The Causes and Consequences of DNA Damage and Chromosomal Instability Induced by Human Papillomavirus.

High-risk human papillomaviruses (HPVs) are the main cause of cervical, oropharyngeal, and anogenital cancers, which are all treated with definitive chemoradiation therapy when locally advanced. HPV proteins are known to exploit the host DNA damage response to enable viral replication and the epithelial differentiation protocol. This has far-reaching consequences for the host genome, as the DNA damage response is critical for the maintenance of genomic stability. HPV+ cells therefore have increased DNA damage, leading to widespread genomic instability, a hallmark of cancer, which can contribute to tumorigenesis. Following transformation, high-risk HPV oncoproteins induce chromosomal instability, or chromosome missegregation during mitosis, which is associated with a further increase in DNA damage, particularly due to micronuclei and double-strand break formation. Thus, HPV induces significant DNA damage and activation of the DNA damage response in multiple contexts, which likely affects radiation sensitivity and efficacy. Here, we review how HPV activates the DNA damage response, how it induces chromosome missegregation and micronuclei formation, and discuss how these factors may affect radiation response. Understanding how HPV affects the DNA damage response in the context of radiation therapy may help determine potential mechanisms to improve therapeutic response.

Cutaneous Applications of the Antiviral Drug Cidofovir: A Review.

Background/Objectives: Cidofovir, an antiviral drug approved for cytomegalovirus retinitis, has emerged as an alternative treatment option for virally induced cutaneous and mucocutaneous conditions, as well as being trialed as a treatment for select neoplasms. In this review, we highlight the existing evidence, clinical uses, and rationale of using cidofovir for the treatment of cutaneous pathologies. Methods: A PubMed database literature search was conducted to identify relevant articles for inclusion in this review. Results: Cidofovir has several cutaneous applications in various formulations including intravenous, topical, and subcutaneous administrations. Primarily through case reports, case series, and retrospective reviews, cidofovir has demonstrated efficacy in treating a variety of virally induced conditions-verruca vulgaris, herpes simplex virus, molluscum contagiosum-as well as in adjuvant treatment for select neoplasms. The drug has shown efficacy in immunocompromised and immunocompetent adults and children alike. Conclusions: The body of literature supports the use of cidofovir as an effective and well-tolerated treatment for many viral cutaneous pathologies, and encourages further study for its use as an adjuvant therapy for neoplastic disease.

Human Papillomavirus-Associated Giant Clear Cell Acanthoma and Squamous Cell Carcinoma: A Rare Case Report and Literature Review.

Clear cell acanthoma (CCA) and squamous cell carcinoma (SCC) represent distinct entities within dermatological oncology, each posing unique diagnostic and therapeutic challenges. CCA is a rare, benign epidermal growth, often not associated with human papillomavirus (HPV) infection, whereas SCC, a more aggressive form of skin cancer, has been linked to both ultraviolet (UV) exposure and HPV. Understanding the co-occurrence of these conditions in a single patient can enhance diagnostic accuracy and therapeutic outcomes. We report a 64-year-old male who underwent an operation for a verruciform lesion in the right groin, which was diagnosed as HPV-positive CCA alongside keratinised SCC. A literature search across January 2024 revealed limited evidence directly linking HPV to CCA, suggesting a need for further investigation. The speculative association between HPV and CCA warrants deeper exploration, especially considering the potential for HPV to contribute to lesion development through indirect mechanisms. The coexistence of CCA and SCC in an elderly patient presents a unique clinical scenario. This emphasises the need for vigilant diagnosis and tailored treatment strategies, highlighting the gap in understanding the pathogenesis of CCA, particularly its potential association with HPV. Further research is crucial for elucidating the complex interactions governing these conditions and for developing targeted interventions.

The Impact of Diagnosis of Human Papillomavirus (HPV) Infection and Electrosurgical Excision Procedure (LEEP) for Cervical Intraepithelial Neoplasia 3 (CIN3) on Women's Sexual Lives.

The aim of the study was to assess sexual health in women who underwent Loop Electrosurgical Excisional Procedure (LEEP) for the treatment of cervical intraepithelial neoplasia 3 (CIN 3). One hundred thirty-one women were enrolled, and the Female Sexual Function Index (FSFI) questionnaire was administered before LEEP and 6 months after the procedure. In almost all of the participants, data revealed a statistically significant worsening in sexual quality of life after LEEP. Therefore, clinicians should be aware of these possible negative effects on sexual behavior, and provide women with appropriate, wide-ranging, and detailed counseling. The data obtained in the present study should help to plan appropriate counseling from communicating HPV diagnosis and medical treatment to CIN3 surgical procedure.

Human Papillomavirus Carcinogenicity and the Need of New Perspectives: Thoughts from a Retrospective Analysis on Human Papillomavirus Outcomes Conducted at the Hospital University of Bari, Apulia, Italy, between 2011 and 2022.

BACKGROUND: The current manuscript's aim was to determine the human papillomavirus (HPV) genotype-specific prevalence and distribution among individuals, males, and females, of different ages in the region of Apulia, Italy, highlighting the possible variables involved in the carcinogenicity mechanism. In addition, we proposed two hypothetical models of HPV's molecular dynamics, intending to clarify the impact of prevention and therapeutic strategies, explicitly modeled by recent survey data. METHODS: We presented clinical data from 9647 participants tested for either high-risk (HR) or low-risk (LR) HPV at the affiliated Bari Policlinic University Hospital of Bari from 2011 to 2022. HPV DNA detection was performed using nested-polymerase chain reaction (PCR) and multiplex real-time PCR assay. Statistical analysis showed significant associations for all genders and ages and both HR- and LR-HPV types. A major number of significant pairwise associations were detected for the higher-risk types and females and lower-risk types and males. RESULTS: The overall prevalence of HPV was 50.5% (n-4.869) vs. 49.5% (n-4.778) of the study population, of which 74.4% (n-3621) were found to be HPV high-risk (HR-HPV) genotypes and 57.7% (n-2.807) low-risk HPV (LR-HPV) genotypes, of which males were 58% and females 49%; the three most prevalent HR-HPV genotypes were HPV 53 (n707-15%), 16 (n704-14%), and 31 (n589-12%), and for LR-HPV, they were 42 (19%), 6 (16%), and 54 (13%); 56% of patients screened for HPV were ≤ 30 years old, 53% were between 31 and 40 years old, 46% were 41-50 and 51-60 years old, and finally, 44% of subjects were >60 years old. CONCLUSIONS: Our study provided comprehensive epidemiological data on HPV prevalence and genotype distribution among 9647 participants, which could serve as a significant reference for clinical practice, and it implied the necessity for more effective screening methods for HPV carcinogenesis covering the use of more specific molecular investigations. Although this is a predominantly descriptive and epidemiological study, the data obtained offer not only a fairly unique trend compared to other studies of different realities and latitudes but also lead us to focus on the HPV infection within two groups of young people and adults and hypothesize the possible involvement of dysbiosis, stem cells, and the retrotransposition mechanism.

Acceptance, Hesitancy, and Refusal Among Parents of Young Girls in Relation to Human Papillomavirus Vaccination: A Study From the Mohammed VI University Hospital Center in Oujda, Morocco.

INTRODUCTION: Morocco has joined the global efforts to eliminate cervical cancer by introducing human papillomavirus (HPV) vaccination into its national immunization program. However, vaccination rates remain insufficient relative to the importance of the vaccine. Therefore, the objective of the study was to understand better the factors associated with acceptance, hesitance, or refusal of the HPV vaccine. MATERIALS AND METHODS: A descriptive and analytical study was conducted among 450 parents of girls of HPV vaccination age at the Mohammed VI University Hospital Center in Oujda, Morocco, over a period of three months. RESULTS: A total of 450 parents were included in the study, most of them being mothers. Most parents were unaware of HPV infection (66%) or the HPV vaccine (62%). The rate of HPV vaccination among the study population was only 33%. Factors associated with nonvaccination included a lack of information about the HPV vaccine (57%), concern about side effects (33%), and unvaccinated family and friends (10%). Parents' intention to vaccinate their daughters was significantly lower in fathers (95% confidence interval, or 95% CI = 0.34-0.66), those with a low educational level (odds ratio, or OR = 0.53; 95% CI = 0.40-0.80), and those with an unfavorable socioeconomic level (OR = 0.41; 95% CI = 0.30-0.56), whereas it was significantly higher in cases of a vaccinated entourage, including friends and family (OR = 1.52; 95% CI = 1.22-2.12), and when vaccination was recommended by a doctor (OR = 1.92; 95% CI = 1.56-2.39). CONCLUSION: The results of our study highlighted parents' lack of information about HPV infection and the HPV vaccine. They also revealed a clear lack of HPV vaccination coverage and identified the reasons for reluctance to vaccinate against HPV. Much remains to be done to increase the rate of HPV vaccination in Morocco.

An Atypical Squamous Papilloma of the Uvula.

Squamous papilloma of the oral cavity is frequently seen in adult patients and is typically presented as painless exophytic granular or cauliflower-like lesions over the tongue, floor of the mouth, palate, uvula, lips, and faucial pillars. Most of the lesions are solitary and grow rapidly to about 0.5 cm. Oral squamous papilloma has no known malignant potential, with conservative surgical excision being the treatment of choice. Recurrence is rare. It occasionally causes symptoms, unless the presentation is atypical, as in our case. An elongated uvula can cause discomfort and reduce a patient's quality of life. This study aims to report an atypical presentation of a squamous papilloma over the soft palate.

Trends in the Prevalence and Mortality of Cervical Cancer in the Kyrgyz Republic.

BACKGROUND: Cervical cancer represents a significant health concern globally and is the fourth most common cancer among women, leading to substantial morbidity and mortality. The primary cause is persistent infection with high-risk human papillomavirus (HPV) types. Despite advancements in prevention, screening, diagnosis, and treatment, disparities in cervical cancer outcomes persist due to variations in screening accessibility and socioeconomic factors. This study focuses on women in the Kyrgyz Republic, highlighting regional disparities and the critical role of early detection. METHODS: A retrospective data analysis was conducted on 1,338 women diagnosed with cervical cancer from 2012 to 2017 in the Kyrgyz Republic. Data were sourced from national health centers, focusing on sociodemographic metrics, clinical staging, and regional distributions. The study utilized statistical analysis to evaluate prevalence and mortality rates, employing the analysis of variance for comparison, significance, and analyzing trends over time. RESULTS: The prevalence of cervical cancer in the Kyrgyz Republic increased from 97.5 per 100,000 females in 2012 to 105.3 per 100,000 in 2017, with mortality rates of 8.3-9.7%. Notably, regional disparities were evident, with Chui, Osh, Jalal-Abad, and Bishkek experiencing increased prevalence rates, while Talas, Issyk-Kul, Naryn, and Batken reported decreased prevalence. Screening programs, particularly the introduction of Pap smears, have been effective in reducing both prevalence and mortality rates in areas with broad population coverage. However, the study highlighted significant variations in outcomes across different regions, underscoring the importance of targeted prevention and screening efforts. CONCLUSIONS: The study confirms the ongoing challenge of cervical cancer in the Kyrgyz Republic, emphasizing the need for improved screening and prevention strategies to address disparities in outcomes. The introduction of pilot screening programs represents a crucial step forward. However, the findings also point to the necessity for enhanced oncological literacy among primary care physicians and the implementation of comprehensive strategies to overcome socioeconomic and regional barriers to effective cervical cancer prevention and treatment. The reduction in prevalence observed in 2016 suggests progress, highlighting the potential impact of focused prevention and screening initiatives.

Exposure to polycyclic aromatic hydrocarbons promotes the progression of low-grade cervical intraepithelial neoplasia: A population-based cohort study in China.

Low-grade cervical intraepithelial neoplasia (CIN1) is an early stage of cervical cancer development. Previously, we reported that exposure to polycyclic aromatic hydrocarbons (PAHs) increases the risk of cervical precancerous lesions, especially in females with a high-risk human papillomavirus (HR-HPV) infection. However, the effects of PAHs on CIN1 progression remain unclear. A community-based prospective cohort study was conducted to evaluate the role of exposure to PAHs in the progression of CIN1. A total of 564 patients diagnosed with CIN1 were followed-up at 6, 12, and 24 months, post-diagnosis, to determine CIN1 reversion, persistence, and progression. Exposure to PAHs was determined by the urine 1-hydroxipayrene (1-OHP) level. Our results showed that the 1-OHP level was significantly higher in patients with CIN1 persistence/progression than in those with reversion (P < .05). High exposure to PAHs increased the risk of CIN1 persistence/progression, with hazard ratios (HR), 95% confidence intervals (CI) of (1.62, 1.24-2.67), (1.98, 1.42-2.75), and (2.37, 1.61-3.49) at 6, 12, and 24 months, post-diagnosis, respectively. The effect was enhanced with HR-HPV positivity, as determined at 6 (1.82, 1.24-2.67), 12 (3.02, 1.74-5.23), and 24 (2.51, 1.48-4.26) months, post-diagnosis. Moreover, the predictive value of exposure to PAHs for CIN1 persistence/progression was higher in HR-HPV-positive patients than in HR-HPV-negative patients. The results revealed that exposure to PAHs facilitated the malignant progression of CIN1 and hindered its reversal, particularly in patients with HR-HPV infection. Our findings provide novel insights into early prevention and intervention targeting the initiation and progression of cervical neoplasia.

Survival outcomes in head and neck squamous cell carcinoma of unknown primary: A national cohort study.

INTRODUCTION: To investigate factors influencing survival in head and neck squamous cell carcinoma of unknown primary (HNSCCUP). METHODS: A retrospective observational cohort study was conducted, over 5 years from January 2015, in UK Head and Neck centres, of consecutive adults undergoing 18F-Fluorodeoxyglucose-PET-CT within 3 months of diagnosis with metastatic cervical squamous cell carcinoma. Patients treated as HNSCCUP underwent survival analysis, stratified by neck dissection and/or radiotherapy to the ipsilateral neck, and by HPV status. RESULTS: Data were received from 57 centres for 965 patients, of whom 482 started treatment for HNSCCUP (65.7% HPV-positive, n = 282/429). Five-year overall survival (OS) for HPV-positive patients was 85.0% (95% CI 78.4-92.3) and 43.5% (95% CI 32.9-57.5) for HPV-negative. HPV-negative status was associated with worse OS, disease-free (DFS), and disease-specific (DSS) survival (all p < .0001 on log-rank test) but not local control (LC) (p = .16). Unilateral HPV-positive disease treated with surgery alone was associated with significantly worse DFS (p < .0001) and LC (p < .0001) compared to radiotherapy alone or combined modalities (5-year DFS: 24.9%, 82.3% and 94.3%; 5-year LC: 41.8%, 98.8% and 98.6%). OS was not significantly different (p = .16). Unilateral HPV-negative disease treated with surgery alone was associated with significantly worse LC (p = .017) (5-year LC: estimate unavailable, 93.3% and 96.6%, respectively). Small numbers with bilateral disease precluded meaningful sub-group analysis. CONCLUSIONS: HPV status is associated with variable management and outcomes in HNSCCUP. Unilateral neck disease is treated variably and associated with poorer outcomes when managed with surgery alone. The impact of diagnostic oropharyngeal surgery on primary site emergence, survival and functional outcomes is unestablished.

Tobacco Smoke Condensate Induces Morphologic Changes in Human Papillomavirus-Positive Cervical Epithelial Cells Consistent with Epithelial to Mesenchymal Transition (EMT) with Activation of Receptor Tyrosine Kinases and Regulation of TGFB.

High-risk human papillomavirus (HR-HPV; HPV-16) and cigarette smoking are associated with cervical cancer (CC); however, the underlying mechanism(s) remain unclear. Additionally, the carcinogenic components of tobacco have been found in the cervical mucus of women smokers. Here, we determined the effects of cigarette smoke condensate (CSC; 3R4F) on human ectocervical cells (HPV-16 Ect/E6E7) exposed to CSC at various concentrations (10-6-100 µg/mL). We found CSC (10-3 or 10 µg/mL)-induced proliferation, enhanced migration, and histologic and electron microscopic changes consistent with EMT in ectocervical cells with a significant reduction in E-cadherin and an increase in the vimentin expression compared to controls at 72 h. There was increased phosphorylation of receptor tyrosine kinases (RTKs), including Eph receptors, FGFR, PDGFRA/B, and DDR2, with downstream Ras/MAPK/ERK1/2 activation and upregulation of common EMT-related genes, TGFB SNAI2, PDGFRB, and SMAD2. Our study demonstrated that CSC induces EMT in ectocervical cells with the upregulation of EMT-related genes, expression of protein biomarkers, and activation of RTKs that regulate TGFB expression, and other EMT-related genes. Understanding the molecular pathways and environmental factors that initiate EMT in ectocervical cells will help delineate molecular targets for intervention and define the role of EMT in the initiation and progression of cervical intraepithelial neoplasia and CC.

Study on the safety and efficacy of HIFU in the treatment of VaIN.

PURPOSE: This study aimed to investigate the safety and efficacy of High-Intensity Focused Ultrasound (HIFU) treatment for vaginal intraepithelial neoplasia(VaIN). METHODS: Retrospective analysis was conducted on clinical, pathological, and follow-up data of 43 patients who underwent HIFU treatment for VaIN at Xiangya Third Hospital of Central South University between January 2018 and December 2022. The preliminary efficacy and safety of HIFU in treating VaIN were discussed. RESULTS: The 36 patients were analyzed, and the average age was 50.09 ± 12.06 years, including 24 patients with VaIN I and 12 patients with VaIN II. Five cases had a history of hysterectomy (4 due to cervical lesions, 1 due to hysteromyoma), and 2 cases had conization of cervical intraepithelial lesions (CIN). All 36 cases were complicated by human papillomavirus (HPV) infection, with 3 cases also having grade I-II CIN and undergoing cervical HIFU treatment. All patients successfully completed the HIFU treatment, with an average treatment time of 5.99 ± 1.25 min, treatment power of 3.5 W, and average total treatment dose of 1118.99 ± 316.20 J. Patients tolerated the treatment well, experiencing only slight pain with VAS score of 3. There was a mild postoperative burning sensation, which resolved within approximately 10-20 min. After 6 follow-up visits, 33 patients (91.66%) achieved cure, 1 patient (2.77%) showed persistence, 2 patients (5.55%) exhibited progression, and 27 patients (75%) tested negative for HPV. At 12 months of follow-up, the results were consistent with those of 6 months. No complications occurred during the procedure and the follow-up period. CONCLUSION: HIFU is a safe and effective treatment for VaIN. However, this study had a small sample size, a relatively short follow-up period, and lacked a control group, requiring further investigation.

Reduced risk of CIN2+ recurrence in women immunized with a 9-valent HPV vaccine post-excision: Retrospective cohort study.

The main aim of our study was to investigate the specific contribution of a 9-valent human papillomavirus vaccine (9vHPV) to the recurrence risk of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) in women vaccinated post-excision. Therefore, we conducted a retrospective monocentric cohort study in women aged 22-49 years undergoing conization between 2014 and 2023. The 9vHPV-vaccinated women were matched to unvaccinated women for age and follow-up duration in a 1:2 ratio to eliminate allocation bias. The risk of CIN2+ recurrence was estimated by the incidence rate ratio using Poisson regression with adjustment for comorbidities, smoking status, nulliparity, CIN grade, positive cone margin, and HPV genotypes. The CIN2+ recurrence rates in 147 women enrolled in the analysis were 18 and 2 cases per 100,000 person-days for unvaccinated and vaccinated women, respectively, during a mean follow-up period of 30 months (±22 months). A reduction in CIN2+ recurrences by 90% (95% confidence interval: 12-99%) was documented in 9vHPV-vaccinated participants compared to women undergoing only surgical excision. Moreover, vaccinated women with a positive cone margin showed a 42% (though non-significant) reduction in relapse (p = .661). Full post-conization vaccination with the 9vHPV contributed to an additional reduction in the risk of CIN2+ recurrence. This finding is consistent with current knowledge and suggests a high adjuvant effect of the 9vHPV vaccine.

Primary Human Papillomavirus Test Uptake and Cervical Cancer Screening Trends in the Midwest, United States.

INTRODUCTION/OBJECTIVES: Despite U.S. Preventive Services Task Force and American Cancer Society endorsement of primary HPV screening, limited published data shows low uptake. PRIMARY AIM: Assess cervical cancer screening rates over time, particularly primary HPV test uptake, among patients in a midwestern practice. SECONDARY AIM: Evaluate associations between sociodemographics and screening adherence. METHODS: Cross-sectional study. Qualifying subjects and type of screening test used were identified by applying ICD-9, ICD-10, lab test, and CPT codes to the Unified Data Platform. Sociodemographics were found through the electronic health record. RESULTS: Primary HPV uptake represented <1% of annual screening from 1/2017 to 1/2022. On 1/1/2022, only 55% of 21 to 29 year old and 63% of 30 to 65 year old were up to date with screening among the studied population. For 21 to 29 year old, compared with White women, Black women were 28% less likely to be screened [RR = 0.72 (0.66-0.79)]. Compared with never-smokers, current smokers were 9% less likely to be screened [RR = 0.91 (0.87-0.96)], past smokers were 14% more likely [RR = 1.14 (1.09-1.2)]. Among 30 to 65 year old, compared with White women, Black women were 14% less likely to be screened [RR = 0.86 (0.81-0.9)]. Compared with never-smokers, current smokers were 21% less likely to be screened [RR = 0.79 (0.77-0.81)], past smokers were 6% less likely [RR = 0.94 (0.92-0.95)]. Jointly considering race, ethnicity, smoking status, Charlson score, and rurality, findings were similar for 21 to 29 year old; Black women were screened less than White women [RR = 0.73 (0.67-0.79)]; current smokers [RR = 0.9 (0.85-0.94)] and past smokers [RR = 1.12 (1.06-1.17)] were screened less than never smokers. For 30 to 65 year old, Black women were screened less than White women [RR = 0.83 (0.79-0.88)]; current smokers [RR = 0.8 (0.78-0.81)] and past smokers [RR = 0.95 (0.93-0.96)] were screened less than never smokers. CONCLUSIONS: Screening rates remained below the Healthy People 2030 goal of 79.2% over time, particularly for younger Black women and current smokers, with minimal use of primary HPV screening.

The Saudi Population's Knowledge and Attitude Towards Human Papillomavirus (HPV) Infection and Its Vaccination.

BACKGROUND: Human papillomavirus (HPV) infection is a major worldwide public health concern that can result in a range of clinical disorders, including cervical cancer. Saudi Arabia, similar to numerous other nations, has difficulties in facing HPV and its impact on society. The high incidence of cervical cancer in Saudi Arabia continues to be a cause for worry, highlighting the need for the adoption of efficient immunization programs. Nevertheless, public hesitation and inadequate knowledge can hinder the acceptance of vaccines. Evaluating public knowledge and attitudes concerning HPV and its vaccination is essential in order to create focused programs that enhance awareness and increase vaccine acceptance. METHODS: This study was cross-sectional in nature, using data from a sample of 516 Saudi participants 18 years and above. The participants completed online questionnaires that were distributed using Google Forms across social media platforms and ensured anonymity. RESULTS: A total of 516 participants made up the sample for this study, which had a predominance of females (83.5%, n=431); the majority aged 18-25 years (78.3%, n=404) and most of them (28.3%, n=146) were from the central region. The study results revealed that 43.7% (n=225) of the participants had a good knowledge level while 56.3% (n=291) of them had a poor level of knowledge about the HPV vaccine. A substantial proportion (35.9%, n=185) of the participants had good knowledge that HPV can be transmitted sexually from one person to another with only 30.2% (n=156) of them being aware that HPV is a common infection that causes cervical cancer (41.5%, n=214) and most of them (76.2%, n=393) knew that cervical cancer can be cured particularly when detected in early stages. The results established statistically significant associations between gender, education level, and occupation with p-values <0.005 (0.023, 0.003 and 0.001 respectively) and level of knowledge about the HPV vaccine. CONCLUSION: The study emphasizes the necessity of implementing focused health education and vaccination initiatives in Saudi Arabia to enhance understanding and attitudes regarding HPV infection and its vaccine. The results can provide guidance to healthcare professionals, legislators, and public health authorities in creating programs that increase knowledge and acceptance of the HPV vaccine, ultimately decreasing the prevalence of HPV-related diseases in the nation.