The Mulher Study: cervical cancer screening with primary HPV testing in Mozambique

Objective To evaluate cervical cancer screening with primary human papillomavirus (HPV) testing in Mozambique, a country with one of the highest burdens of cervical cancer globally. Methods Women aged 30­49 years were prospectively enrolled and offered primary HPV testing using either self- collected or provider- collected specimens. Patients who tested positive for HPV underwent visual assessment for treatment using visual inspection with acetic acid to determine eligibility for thermal ablation. If ineligible, they were referred for excision with a loop electrosurgical excision procedure, for cold knife conization, or for cervical biopsy if malignancy was suspected. Results Between January 2020 and January 2023, 9014 patients underwent cervical cancer screening. Median age was 37 years (range 30­49) and 4122 women (45.7%) were patients living with HIV. Most (n=8792, 97.5%) chose self- collection. The HPV positivity rate was 31.1% overall and 39.5% among patients living with HIV. Of the 2805 HPV- positive patients, 2588 (92.3%) returned for all steps of their diagnostic work- up and treatment, including ablation (n=2383, 92.1%), loop electrosurgical excision procedure (n=169, 6.5%), and cold knife conization (n=5, 0.2%). Thirty- one patients (1.2%) were diagnosed with cancer and referred to gynecologic oncology. Conclusion It is feasible to perform cervical cancer screening with primary HPV testing and follow- up in low- resource settings. Participants preferred self- collection, and the majority of screen- positive patients completed all steps of their diagnostic work- up and treatment. Our findings provide important information for further implementation and scale- up of cervical cancer screening and treatment services as part of the WHO global strategy for the elimination of cervical cancer.

Promise and Perils of Primary HPV Testing.

Cervical cancer screening has reduced morbidity and mortality in many countries, but efforts to optimize screening modalities and schedules are ongoing. Using data from a randomized trial conducted in British Columbia, Canada, in conjunction with a provincial screening registry, Gottschlich and colleagues demonstrated that the estimated risk for precancerous disease (cervical intraepithelial neoplasia grades 2 or worse) at 8 years following a negative human papillomavirus (HPV) test was similar to the current standard of care (Pap testing after 3 years). The study supports extending screening intervals for those with a negative HPV test beyond currently recommended 5-year intervals. In an ideal world, the resources saved through less frequent routine cervical screening could be redirected to increasing screening uptake and follow-up of abnormalities to improve equity in cervical cancer prevention. However, implementation of extending screening intervals remains less than straightforward in settings with fragmented healthcare systems that lack information systems to support patient call/recall, such as the United States. To achieve the full promise of primary HPV testing, stakeholders at every level must commit to identifying and addressing the diverse spectrum of barriers that undergird existing inequities in care access, appropriately resource implementation strategies, and improve health information systems. See related article by Gottschlich et al., p. 904.

Prevalence and correlates of Human Papillomavirus infection in females from Southern Province, Zambia: A cross-sectional study.

BACKGROUND: Human papillomavirus (HPV) infection is strongly associated with cervical cancer with almost all cases being associated with the infection. Cervical cancer is the leading cause of cancer death among women in Zambia and the fourth leading cause of cancer death in women worldwide. However, there is limited data on the burden and associated factors of HPV in sub-Saharan Africa. This study therefore aimed to determine the prevalence and correlates of HPV infection in the Southern province of Zambia. METHODS: This was a cross-sectional study conducted at Livingstone University Teaching Hospital (LUTH) among 4,612 women from different districts of the southern province being screened for HPV infection between September 2021 and August 2022. Demographic and clinical data were collected from an existing laboratory programmatic database. Multivariable logistic regression was used to estimate the factors associated with HPV infection. RESULTS: The study participants had a median age of 39 years [interquartile range (IQR) 30, 47]. The prevalence of HPV infection was 35.56% (95%CI). At multivariable analysis, the factors associated with a positive HPV result were younger age (adjusted odds ratio (AOR) 0.98; 95% confidence interval (CI) 0.98-0.99; p. value 0.001), having provider collected sample (AOR 2.15; 95%CI 1.66-2.79; p. value <0.001) and living with HIV (AOR 1.77; 95%CI 1.22-2.55; p. value <0.002). CONCLUSION: The prevalence of HPV in women in the southern province of Zambia is high, and likely influenced by age and HIV status. Additionally, the outcome of the HPV test is affected by the sample collection method. Therefore, there is a necessity to enhance HPV and cervical cancer screening, especially among people with HIV.

HPV Extended Genotyping to Triage Abnormal Cervical Cancer Screens-Balancing the Harms and Benefits of an Additional Triage Test before Direct Colposcopy Referral.

The Netherlands' cervical cancer screening program transitioned to primary human papillomavirus (HPV) screening in 2017. After the introduction of HPV-based screening, the country saw increases in colposcopy referral rates and detections of low-grade lesions. In July 2022, genotyping was introduced, and those with borderline or mild dyskaryotic (BMD) cytologic abnormalities were only referred to colposcopy if positive for HPV type 16 or 18, and repeat screening otherwise. In this article, various strategies using extended genotyping (HPV16/18/31/33/45/52/58) as a triage test after an abnormal screen were explored using data from HPV-positive participants with normal or BMD cytology in the Population-Based Screening Study Amsterdam (POBASCAM) trial. The authors assessed positive and negative predictive values and colposcopy referral rates for each strategy using extended genotyping to triage women to either direct referral to colposcopy or repeat screening. Direct referral did not meet positive and negative predictive value thresholds for efficiency for any strategies. However, the authors note that direct referral may nonetheless be useful among those with BMD due to minimal increases in colposcopy referrals and concerns of loss to follow-up at repeat screening. These findings demonstrate the potential utility of extended genotyping as a triage test in primary HPV screening programs. The results should be considered alongside the fact that referral to repeat screening may result in loss of engagement of women who need treatment to prevent invasive cancer. See related article by Kroon et al., p. 1037.

Distribution and diagnostic value of single and multiple high-risk HPV infections in detection of cervical intraepithelial neoplasia: A retrospective multicenter study in China.

The risk associated with single and multiple human papillomavirus (HPV) infections in cervical intraepithelial neoplasia (CIN) remains uncertain. This study aims to explore the distribution and diagnostic significance of the number of high-risk HPV (hr-HPV) infections in detecting CIN, addressing a crucial gap in our understanding. This comprehensive multicenter, retrospective study meticulously analyzed the distribution of single and multiple hr-HPV, the risk of CIN2+, the relationship with CIN, and the impact on the diagnostic performance of colposcopy using demographic information, clinical histories, and tissue samples. The composition of a single infection was predominantly HPV16, 52, 58, 18, and 51, while HPV16 and 33 were identified as the primary causes of CIN2+. The primary instances of dual infection were mainly observed in combinations such as HPV16/18, HPV16/52, and HPV16/58, while HPV16/33 was identified as the primary cause of CIN2+. The incidence of hr-HPV infections shows a dose-response relationship with the risk of CIN (p for trend <0.001). Compared to single hr-HPV, multiple hr-HPV infections were associated with increased risks of CIN1 (1.44, 95% confidence interval [CI]: 1.20-1.72), CIN2 (1.70, 95% CI: 1.38-2.09), and CIN3 (1.08, 95% CI: 0.86-1.37). The colposcopy-based specificity of single hr-HPV (93.4, 95% CI: 92.4-94.4) and multiple hr-HPV (92.9, 95% CI: 90.8-94.6) was significantly lower than negative (97.9, 95% CI: 97.0-98.5) in detecting high-grade squamous intraepithelial lesion or worse (HSIL+). However, the sensitivity of single hr-HPV (73.5, 95% CI: 70.8-76.0) and multiple hr-HPV (71.8, 95% CI: 67.0-76.2) was higher than negative (62.0, 95% CI: 51.0-71.9) in detecting HSIL+. We found that multiple hr-HPV infections increase the risk of developing CIN lesions compared to a single infection. Colposcopy for HSIL+ detection showed high sensitivity and low specificity for hr-HPV infection. Apart from HPV16, this study also found that HPV33 is a major pathogenic genotype.

Epidemiological distribution of high-risk human papillomavirus genotypes and associated factors among patients with esophageal carcinoma at Bugando medical center in Mwanza, Tanzania.

BACKGROUND: Esophageal carcinoma is a growing concern in regions that have a high incidence of human papillomavirus (HPV) infection such as East Africa. HPV, particularly the high-risk genotypes, is increasingly recognized as a risk factor for esophageal carcinoma. We set out to investigate the prevalence and associated factors of high-risk HPV in formalin-fixed paraffin-embedded (FFPE) tissue blocks with esophageal carcinoma at Bugando Medical Center, a tertiary referral hospital in Mwanza, Tanzania, East Africa. METHODS: A total of 118 esophageal carcinoma FFPE tissue blocks, collected from January 2021 to December 2022, were analyzed. Genomic DNA was extracted from these tissues, and multiplex polymerase chain reaction (PCR) was performed to detect HPV using degenerate primers for the L1 region and type-specific primers for detecting HPV16, HPV18, and other high-risk HPV genotypes. Data were collected using questionnaires and factors associated with high-risk HPV genotypes were analyzed using STATA version 15 software. RESULTS: Of the 118 patients' samples investigated, the mean age was 58.3 ± 13.4 years with a range of 29-88 years. The majority of the tissue blocks were from male patients 81/118 (68.7%), and most of them were from patients residing in Mwanza region 44/118 (37.3%). Esophageal Squamous Cell Carcinoma (ESCC) was the predominant histological type 107/118 (91.0%). Almost half of the tissue blocks 63/118 (53.3%) tested positive for high-risk HPV. Among these, HPV genotype 16 (HPV16) was the most common 41/63 (65.1%), followed by HPV genotype 18 (HPV18) 15/63 (23.8%), and the rest were other high-risk HPV genotypes detected by the degenerate primers 7/63 (11.1%). The factors associated with high-risk HPV genotypes were cigarette smoking (p-value < 0.001) and alcohol consumption (p-value < 0.001). CONCLUSION: A substantial number of esophageal carcinomas from Bugando Medical Center in Tanzania tested positive for HPV, with HPV genotype 16 being the most prevalent. This study also revealed a significant association between HPV status and cigarette smoking and alcohol consumption. These findings provide important insights into the role of high-risk HPV in esophageal carcinoma in this region.

Evaluation of female university students' knowledge, attitudes, and practices toward human papillomavirus infection and vaccination. Multicenter cross-sectional study.

INTRODUCTION: Having good knowledge and a favorable attitude toward human papillomavirus (HPV) and HPV vaccinations is the cornerstone for increasing the use of HPV vaccinations and preventing cervical cancer. The objective of this study was to evaluate the level of knowledge, attitudes, and practices regarding HPV and HPV vaccinations, as well as to identify associated factors among female undergraduate health science students at both the University of Gondar (UoG) and Bahir Dar University (BDU), Amhara, Ethiopia. METHODS: Institutional-based multicenter descriptive cross-sectional study was conducted from June 1, 2023, to July 30, 2023. A multistage sampling technique was used to select 633 female undergraduate health science students, and data were collected using a structured, self-administered questionnaire. The data were coded, entered in Epi-data, and exported to SPSS for analysis. Variables with a P-value < 0.25 in the bivariate analysis were inserted in a multivariate logistic regression model, and those with a P-value of < 0.05 in the multivariate binary logistic regression were considered statistically significant factors for knowledge, attitude, and practice regarding HPV and vaccine against it. RESULTS: The study included 600 participants with a mean age of 20.8 ± 0.75 years. Using Bloom's cutoff points for the KAP study, among the participants, 436 (72.7%) had good knowledge about HPV, whereas 315 (52.5%) had good knowledge about HPV vaccinations. More than half of the participants, 359 (59.8%) heard about HPV vaccinations in Ethiopia. More than half of the participants, 342 (57%) had favorable attitudes toward HPV vaccinations. Only 261 (43.5%) participants believed the HPV vaccine was safe and effective. All participants had never been tested for HPV, and 471 (78.5%) refused to have their samples for regular HPV testing. The factors like ages between 21 and 23 years (AOR, 2.12, 95% CI: 1.22-3.09) and favorable attitudes toward HPV vaccinations (AOR: 1.88; 95%, CI: 1.15-3.41) were associated with the participant's knowledge about HPV vaccinations. Having good knowledge about the virus (AOR: 1.92; 95%, CI: 1.11-5.88) and its vaccine (AOR:1.60; 95%CI: 1.07-2.47) were factors associated with the attitude of the participants about HPV vaccinations. Additionally, HPV vaccination practice was significantly associated with the attitude of the participants toward HPV vaccinations (AOR: 1.85; 95%CI: 1.15-3.45), knowledge about HPV (AOR: 1.18; 95%CI: 0.55-5.50), and HPV vaccinations (AOR: 1.85; 95%CI: 1.08-2.44). CONCLUSION: This study revealed that half of the students had good knowledge and a favorable attitude toward HPV vaccinations, but there was poor HPV vaccination practice. There is still a need for continued health education, training, and counseling services for students to strengthen HPV vaccination practices, improve students' attitudes and knowledge about the benefits of vaccination, and improve counseling abilities against HPV-induced cancer.

Morphologic Spectrum of HPV-associated Sinonasal Carcinomas.

BACKGROUND: High-risk human papillomavirus (HR-HPV) infection has been increasingly recognized as a risk factor for sinonasal tract carcinomas. However the prevalence and prognostic significance of HPV-associated sinonasal carcinomas is not well known due to limited studies and inconsistency in HPV testing modalities in literatures. Morphologically, HPV-associated sinonasal carcinomas encompass a diverse group of tumors. HPV-associated sinonasal adenocarcinoma has not been reported. The purpose of this study was to determine the prevalence, morphologic spectrum and prognostic implication of HPV-associated sinonasal carcinomas. METHODS: This cohort included 153 sinonasal carcinomas. Tissue microarrays were constructed. P16 immunohistochemistry and HR-HPV E6/7 in-situ Hybridization (ISH) were performed. Carcinomas were deemed HPV-associated based on a positive ISH testing. Clinicopathologic data was collected. RESULTS: 28/153 (18%) sinonasal carcinomas were HPV-associated. HPV-associated carcinomas consisted of 26 (93%) squamous cell carcinomas and variants, 1 (3.5%) HPV-related multiphenotypic sinonasal carcinoma and 1 (3.5%) adenocarcinoma. The HPV-associated adenocarcinoma closely resembled HPV-associated endocervical adenocarcinoma morphologically. HPV-associated carcinomas occurred in 8 (29%) women and 20 (71%) men with a median age of 66 years old. HPV-associated carcinomas were predominantly located at nasal cavity. A trend toward improved overall survival and progression free survival in HPV-associated carcinomas patients was observed, yet without statistical significance. CONCLUSION: Our study identifies a novel HPV-associated sinonasal adenocarcinoma subtype, highlights the broad morphologic spectrum of HPV-associated sinonasal carcinomas, and supports routine p16 testing during pathology practice regardless of tumor subtype followed by a confirmatory HR-HPV testing. This practice is critical for studying the clinical behavior of HPV-associated sinonasal carcinomas.

CER818: A Highly Specific and Sensitive HPV L1 High-Risk Serological Lateral Flow Rapid Test for Early Detection of Cervical Cancer and Its Precursor Lesions.

Objective: The objective of the study is to validate a new human papillomavirus (HPV) L1 high-risk specific serological assay in a case-control study. Methods: Serum samples of 138 patients (cervical intraepithelial neoplasia (CIN) 1, 2, and 3 and cervical cancer), 21 vaccinees, and 246 female controls were tested for the presence of HPV L1 high-risk specific antibodies. Results: HPV L1 high-risk antibodies were detected in 100% of the CIN1 and 2, 86.6% of the CIN3 and 82.4% of the cervical cancer cases, 100% of the vaccinees, and 3.9% of the female controls. Area under the curve (AUC) was calculated with 0.91 for controls versus CIN2+, 0.923 for controls versus CIN1+, and 0.968 for controls versus CIN1/2. Conclusion: The HPV L1 high-risk specific serological lateral flow rapid test shows promising data in the field of early detection of HPV high-risk induced cervical cancer and its precursor lesions. This easy-to-use, robust, and affordable approach could offer a chance to reach women in low- or middle-income countries (LMICs) that could not be reached by HPV molecular testing-based cervical cancer screening programs.

Genome composition-based deep learning predicts oncogenic potential of HPVs.

Human papillomaviruses (HPVs) account for more than 30% of cancer cases, with definite identification of the oncogenic role of viral E6 and E7 genes. However, the identification of high-risk HPV genotypes has largely relied on lagged biological exploration and clinical observation, with types unclassified and oncogenicity unknown for many HPVs. In the present study, we retrieved and cleaned HPV sequence records with high quality and analyzed their genomic compositional traits of dinucleotide (DNT) and DNT representation (DCR) to overview the distribution difference among various types of HPVs. Then, a deep learning model was built to predict the oncogenic potential of all HPVs based on E6 and E7 genes. Our results showed that the main three groups of Alpha, Beta, and Gamma HPVs were clearly separated between/among types in the DCR trait for either E6 or E7 coding sequence (CDS) and were clustered within the same group. Moreover, the DCR data of either E6 or E7 were learnable with a convolutional neural network (CNN) model. Either CNN classifier predicted accurately the oncogenicity label of high and low oncogenic HPVs. In summary, the compositional traits of HPV oncogenicity-related genes E6 and E7 were much different between the high and low oncogenic HPVs, and the compositional trait of the DCR-based deep learning classifier predicted the oncogenic phenotype accurately of HPVs. The trained predictor in this study will facilitate the identification of HPV oncogenicity, particularly for those HPVs without clear genotype or phenotype.

Proximity ligation-based sequencing for the identification of human papillomavirus genomic integration sites in formalin-fixed paraffin embedded oropharyngeal squamous cell carcinomas.

Human papillomavirus (HPV) infections are an increasing cause of oropharyngeal squamous cell carcinomas (OPSCC). Integration of the viral genome into the host genome is suggested to affect carcinogenesis, however, the correlation with OPSCC patient prognosis is still unclear. Research on HPV integration is hampered by current integration detection technologies and their unsuitability for formalin-fixed paraffin-embedded (FFPE) tissues. This study aims to develop and validate a novel targeted proximity-ligation based sequencing method (targeted locus amplification/capture [TLA/TLC]) for HPV integration detection in cell lines and FFPE OPSCCs. For the identification of HPV integrations, TLA/TLC was applied to 7 cell lines and 27 FFPE OPSCCs. Following preprocessing steps, a polymerase chain reaction (PCR)-based HPV enrichment was performed on the cell lines and a capture-based HPV enrichment was performed on the FFPE tissues before paired-end sequencing. TLA was able to sequence up to hundreds of kb around the target, detecting exact HPV integration loci, structural variants, and chromosomal rearrangements. In all cell lines, one or more integration sites were identified, in accordance with detection of integrated papillomavirus sequences PCR data and the literature. TLC detected integrated HPV in 15/27 FFPE OPSCCs and identified simple and complex integration patterns. In general, TLA/TLC confirmed PCR data and detected additional integration sites. In conclusion TLA/TLC reliably and robustly detects HPV integration in cell lines and FFPE OPSCCs, enabling large, population-based studies on the clinical relevance of HPV integration. Furthermore, this approach might be valuable for clonality assessment of HPV-related tumors in clinical diagnostics.

Prevalence of human papilloma virus among cervical cancer patients in India: A systematic review and meta-analysis.

BACKGROUND: Cervical cancer, predominantly caused by the human papillomavirus (HPV), is a major health challenge in India, with high morbidity and mortality rates. Given India's vast geographic and socio-economic diversity, understanding regional variations in HPV prevalence is crucial for developing targeted and effective public health interventions. This systematic review and meta-analysis were conducted to elucidate the prevalence of HPV among cervical cancer patients in India. METHODS: A literature search was executed across PubMed, EMBASE, and Web of Science up to December 07, 2023. Observational studies reporting HPV prevalence among cervical cancer patients in India are included. A Modified Newcastle-Ottawa scale was used for quality assessment. A random-effects meta-analysis was used to determine pooled HPV prevalence, and heterogeneity was evaluated using the I² statistic. Subgroup and sensitivity analyses were performed to assess result stability and investigate heterogeneity sources. All statistical analyses were performed using R software version 4.3. RESULTS: The meta-analysis included 17 studies with a total of 2529 cervical cancer cases, of which 1977 were HPV-positive. The pooled HPV prevalence was 85% (95% CI: 71-92%), with substantial heterogeneity (I²â€…= 94%). Subgroup analysis by geographic zones showed notable differences: South (88%, 95% CI: 76-95%), North (73%, 95% CI: 1-100%), East (99%, 95% CI: 1-100%), Central (71%, 95% CI: 54-84%), and West (77%, 95% CI: 0-100%). Sensitivity analysis demonstrated the consistency of the results, and a reanalysis, excluding influential studies, yielded a prevalence of 82% (95% CI: 67-91%). CONCLUSION: Our analysis reveals a high prevalence of HPV in cervical cancer patients in India, with significant regional variations. The observed heterogeneity highlights the complexity of HPV epidemiology in India and necessitates further research to explore underlying causes and regional characteristics. Future studies should aim to expand geographic representation and deepen understanding of the factors contributing to the variability in HPV prevalence.

Manipulating host secreted protein gene expression: an indirect approach by HPV11/16 E6/E7 to suppress PBMC cytokine secretion.

Human papillomavirus (HPV) 11/16 E6/E7 proteins have been recognized to be pivotal in viral pathogenesis. This study sought to uncover the potential mechanisms of how HPV11/16 E6/E7-transfected keratinocytes inhibit cytokine secretion in peripheral blood mononuclear cells (PBMC). Upon co-culturing HPV11/16 E6/E7-transfected keratinocytes with PBMC in a non-contact manner, we observed a marked decrease in various cytokines secreted by PBMC. To determine if this suppression was mediated by specific common secreted factors, we conducted transcriptomic sequencing on these transfected cells. This analysis identified 53 common differentially secreted genes in all four HPV-transfected cells. Bioinformatics analysis demonstrated these genes were predominantly involved in immune regulation. Results from quantitative PCR (qPCR) and an extensive literature review suggested the downregulation of 12 genes (ACE2, BMP3, BPIFB1, CLU, CST6, CTF1, HMGB2, MMP12, PDGFA, RNASE7, SULF2, TGM2), and upregulation of 7 genes (CCL17, CCL22, FBLN1, PLAU, S100A7, S100A8, S100A9), may be crucial in modulating tumor immunity and combating pathogenic infections, with genes S100A8 and S100A9, and IL-17 signaling pathway being particularly noteworthy. Thus, HPV11/16 E6/E7 proteins may inhibit cytokine secretion of immune cells by altering the expression of host-secreted genes. Further exploration of these genes may yield new insights into the complex dynamics of HPV infection.

Prevalence, risk factors and genotype distribution of human papillomavirus infection among women with and without invasive cervical cancer: Findings from a hospital-based study in Bihar, India.

Background Human papillomavirus (HPV) infection is largely responsible for the development of invasive cervical cancer (ICC). Its prevalence, risk factors and genotype distribution among women residing in Bihar (third most populous Indian state) with and without ICC are not well known. Methods In this hospital-based study, we followed up 1439 participants with cytology and HPV report. HPV detection and genotyping were performed using the TaqMan-based real-time PCR method. Clinical and sociodemographic data were collected and analysed using statistical methods. Results The overall prevalence of HPV infection was 37.3% (537/1439) and 11 different types of HPV genotypes were observed. Higher HPV positivity was found in premalignant, intraepithelial and invasive malignant lesions of the cervix; 73.8% (93/126) of atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H) and high-grade squamous intraepithelial lesions (HSIL) and 93.4% (114/122) of invasive malignancies were infected with HPV in comparison to only 26.1% (245/938) of negative for intraepithelial lesion or malignancy (NILM) cytology. Moreover, HPV was found in 95.2% (236/248) of histologically confirmed cases of carcinoma cervix. HPV16 and HPV18 infections were reported in 78.2% (194/248) and 8.9% (22/248), respectively. The remaining patients had infection with other high-risk strains/co-infection with multiple strains or were HPV-negative. Various socio-demographic factors including women >50 years of age, >10 years of marriage and high parity were significantly associated with HPV infection. Conclusion Our data suggest that HPV16 infection may be the major cause for ICC among women residing in Bihar. Our findings may serve as a baseline for developing an appropriate screening and vaccination strategy for Bihar.

Factors that influence the uptake of human papillomavirus vaccine among preadolescent girls in South Africa: A Scoping Review.

Human papillomavirus (HPV) infection is a sexually transmitted infection which causes cancer, especially cervical cancer. HPV infection and cervical cancer are a public health concern in South Africa. Primary prevention interventions, such as vaccination against cervical cancer, have been rolled out in the country. However, the uptake of the vaccine faces challenges due to various factors. The aim of the review was to identify factors which influence the uptake of the vaccine. A six-step framework developed by Levac, Colquhon and O'Brien was adopted to guide this scoping review. The articles were searched in the following databases: EBSCOhost, PubMed, CINAHL and Google scholar. The search, conducted from May to July 2023 was limited to articles published in English between 2008-2023 and those conducted in Africa. The results showed that most studies were conducted in sub-Saharan Africa, with majority of the studies being from Nigeria. Subthemes were extracted from the articles and categorised under the four themes of the Social Ecological Model. The four themes used from the Social Ecological Model were individual factors; interpersonal factors; community and societal factors, and organisational factors and public policy. The subthemes were socioeconomic and sociodemographic of parents, knowledge, fear and mistrust, family structure and proximity to cancer/STI, misinformation from social media, religion, culture and tradition, free vaccination programme and lack of engagement. The identified gap in literature was a lack of studies of factors which influence HPV vaccination uptake in South Africa and qualitative studies that explore and provide the factors influencing uptake. We conclude that in designing effective interventions for the uptake of HPV vaccines, it is important to consider influential factors that are tailor-made for specific demographics.

L'infection par le virus du papillome humain (VPH) est une infection sexuellement transmissible qui provoque le cancer, notamment le cancer du col de l'utérus. L'infection au VPH et le cancer du col de l'utérus constituent un problème de santé publique en Afrique du Sud. Des interventions de prévention primaire, telles que la vaccination contre le cancer du col de l'utérus, ont été déployées dans le pays. Cependant, l'adoption du vaccin se heurte à des difficultés dues à divers facteurs. Le but de l'examen était d'identifier les facteurs qui influencent l'adoption du vaccin. Un cadre en six étapes élaboré par Levac, Colquhon et O'Brien a été adopté pour guider cet examen de la portée. Les articles ont été recherchés dans les bases de données suivantes : EBSCOhost, PubMed, CINAHL et Google Scholar. La recherche, menée de mai à juillet 2023, s'est limitée aux articles publiés en anglais entre 2008-2023 et à ceux menés en Afrique. Les résultats ont montré que la plupart des études ont été menées en Afrique subsaharienne, la majorité des études provenant du Nigeria. Les sous-thèmes ont été extraits des articles et classés sous les quatre thèmes du modèle socio-écologique. Les quatre thèmes utilisés dans le modèle socio-écologique étaient des facteurs individuels ; facteurs interpersonnels; les facteurs communautaires et sociétaux, ainsi que les facteurs organisationnels et les politiques publiques. Les sous-thèmes étaient socio-économiques et sociodémographiques des parents, connaissances, peur et méfiance, structure familiale et proximité du cancer/IST, désinformation provenant des médias sociaux, religion, culture et tradition, programme de vaccination gratuit et manque d'engagement. La lacune identifiée dans la littérature était le manque d'études sur les facteurs qui influencent le recours à la vaccination contre le VPH en Afrique du Sud et d'études qualitatives qui explorent et fournissent les facteurs qui influencent le recours à la vaccination. Nous concluons que lors de la conception d'interventions efficaces pour l'adoption des vaccins contre le VPH, il est important de prendre en compte les facteurs influents adaptés à des données démographiques spécifiques.

High-risk human papillomavirus infection and cervical cytopathology: relationship with cervical nitric oxide levels.

BACKGROUND: Nitric oxide (NO) may contribute to the persistence of high-risk human papillomavirus (hrHPV) infection, which has been linked to the development of premalignant lesions and cervical cancer. Our study aimed to examine the relationship between cervical NO metabolite (NOx) levels, hrHPV infection, and cytopathological findings. Additionally, we assessed cervical NOx levels as a biomarker for predicting hrHPV infection and epithelial atypia. METHODS: The study involved 74 women who attended the Gynecology and Obstetrics outpatient clinics at Cairo University Hospitals between November 2021 and August 2022. Cervical samples were subjected to Pap testing, assessment of NOx levels by the Griess method, and detection of hrHPV DNA by real-time polymerase chain reaction. RESULTS: High-risk HPV was detected in 37.8% of women. EA was found in 17.1% of cases, with a higher percentage among hrHPV-positive than negative cases (35.7% vs. 4.3%, p = 0.001). The most prevalent hrHPV genotype was HPV 16 (89.3%). The cervical NOx level in hrHPV-positive cases was significantly higher (37.4 µmol/mL, IQR: 34.5-45.8) compared to negative cases (2.3 µmol/mL, IQR: 1.2-9.8) (p = < 0.001). Patients with high-grade atypia showed significantly higher NOx levels (38.0 µmol/mL, IQR: 24.6-94.7) in comparison to NILM and low-grade atypia cases (5.0 µmol/mL, IQR: 1.6-33.3 and 34.5 µmol/mL, IQR: 11.7-61.7, respectively) (p = 0.006). Although the NOx levels among hrHPV-positive cases with low-grade atypia (40.4 µmol/mL, IQR: 33.3‒61.8) were higher than those with NILM (36.2 µmol/mL, IQR: 35.7‒44.0) and high-grade atypia (38.0 µmol/mL, IQR: 24.6‒94.7), the difference was not significant (p = 0.771). ROC curve analysis indicated that the cervical NOx cut-off values of > 23.61 µmol/mL and > 11.35 µmol/mL exhibited good diagnostic accuracy for the prediction of hrHPV infection and EA, respectively. CONCLUSIONS: The high prevalence of hrHPV infection, particularly HPV 16, in our hospital warrants targeted treatment and comprehensive screening. Elevated cervical NOx levels are associated with hrHPV infection and high-grade atypia, suggesting their potential use as biomarkers for predicting the presence of hrHPV and abnormal cytological changes.

The landscape of circulating tumor HPV DNA and TTMV-HPVDNA for surveillance of HPV-oropharyngeal carcinoma: systematic review and meta-analysis.

BACKGROUND: Human papilloma virus (HPV) related cancers of the oropharynx are rapidly increasing in incidence and may soon represent the majority of all head and neck cancers. Improved monitoring and surveillance methods are thus an urgent need in public health. MAIN TEXT: The goal is to highlight the current potential and limitations of liquid biopsy through a meta analytic study on ctHPVDNA and TTMV-HPVDNA. It was performed a Literature search on articles published until December 2023 using three different databases: MEDLINE, Embase, and Cochrane Library. Studies that evaluated post-treatment ctHPVDNA and TTMV-HPVDNA in patients with HPV + OPSCC, studies reporting complete data on the diagnostic accuracy in recurrence, or in which the number of true positives, false positives, true negatives, and false negatives was extractable, and methods of detection of viral DNA clearly defined. The meta-analysis was conducted following the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) reporting guidelines. The aim of this meta-analysis was to evaluate the sensitivity, specificity, and accuracy of ctHPVDNA and TTMV by ddPCR to define its efficacy in clinical setting for the follow up of HPV-OPSCC. CONCLUSION: The 12 studies included in the meta-analysis provided a total of 1311 patients for the analysis (398 valuated with ctHPVDNA and 913 with TTMV-HPVDNA). Pooled sensitivity and specificity were 86% (95% CI: 78%-91%) and 96% (95% CI: 91%-99%), respectively; negative and positive likelihood ratios were 0.072 (95% CI: 0.057-0.093) and 24.7 (95% CI: 6.5-93.2), respectively; pooled DOR was 371.66 (95% CI: 179.1-918). The area under the curve (AUC) was 0.81 (95% CI, 0.67-0.91). Liquid biopsy for the identification of cell free DNA might identify earlier recurrence in HPV + OPSCC patients. At the present time, liquid biopsy protocol needs to be standardized and liquid biopsy cannot yet be used in clinical setting. In the future, a multidimensional integrated approach which links multiple clinical, radiological, and laboratory data will contribute to obtain the best follow-up strategies for the follow-up of HPV-OPSCC.

HPV vaccine behaviors and intentions among a diverse sample of women aged 27-45 years: implications for shared clinical decision-making.

BACKGROUND: The Advisory Committee on Immunization Practices issued a shared clinical decision-making (SCDM) recommendation for HPV vaccination in persons aged 27-45. Since expanded eligibility for the vaccine was issued, little information has been available about HPV vaccine behaviors and intentions among women in this age group. METHODS: We conducted a cross-sectional online survey among women aged 27-45 years recruited through a Qualtrics™ respondent panel (N = 324) to answer the following questions (1) What is the prevalence of HPV vaccination among a diverse sample of adult women aged 27-45 years? (2) What are the characteristics of those who have or have not previously been vaccinated? and (3) What factors are associated with the intention to obtain the HPV vaccine among those who had never been vaccinated? Multivariable logistic regression analyses estimated adjusted odds ratios (AORs) and 95% confidence intervals (95% CIs). RESULTS: Only 31.1% had at least one dose of the HPV vaccine. In multivariable analyses, those more likely to have been vaccinated were younger and were more likely to believe that the vaccine was effective. Of those unvaccinated or unsure, 54.8% indicated they were likely to get vaccinated in the future. Factors associated with future vaccine intention (compared to those not intending) included beliefs about vaccine testing, perceived likelihood of HPV infection, greater comfort in asking one's provider for vaccination, and prior negative healthcare experiences. CONCLUSIONS: Our findings suggest that many women in this age group are interested in HPV vaccination. While the recommendation is for SCDM rather than routine vaccination for all women in this age group, efforts to promote informed decision-making among mid-adult women may include educating women about the rigorous vaccine testing and approval process, their risk factors for HPV infection, and encouraging them to engage in SCDM with their medical providers. Targeted efforts to reach women who have had negative experiences with healthcare may also be needed.

Uptake of human papilloma virus vaccination among adolescent girls living with HIV in Uganda: A mixed methods study.

BACKGROUND: Human Papilloma Virus (HPV) vaccination can prevent more than 90% of cancers caused by HPV. Although this vaccination is recommended and provided at no cost to all adolescent girls aged 9 to19 years in Uganda, its uptake remains low. We sought to determine the uptake of, and factors associated with HPV vaccination among adolescent girls living with HIV in Uganda. METHODS: We conducted an explanatory sequential mixed methods study, among adolescent girls living with HIV, attending HIV care at the Mulago ISS HIV clinic in Kampala, Uganda. We administered a structured questionnaire to elicit data on HPV vaccination and its covariates to a systematic random sample of 264 adolescent girls with HIV. A participant who had received all the three recommended HPV vaccine doses was classified as fully vaccinated. We then conducted four focus group discussions among adolescent girls living with HIV (n = 32), eight in-depth interviews among their parents and five Key informant interviews among their healthcare providers. We conducted descriptive statistics and logistic regression analyses for the quantitative data before thematic analysis for the qualitative data. RESULT: Of 264 adolescent girls, 31% (83/264) had at least one HPV vaccine dose; 22% (59/264) two doses, while 8.0% (21/264) were fully vaccinated (received three doses). While most participants received their first and second doses (48% (40/83)) and 57.6% (34/59), respectively) from school, the largest number of participants (47.1% (12/21)) received their third dose at community outreaches. Participants who received counseling from community members were three times more likely to get fully vaccinated compared to those who did not receive counseling (aOR 3.28, Cl:1.07-10.08, P = 0.038). From the qualitative follow-up, three major themes were identified: (1): Limited information about HPV vaccination, which gave room for misconceptions and doubts about the vaccine; (2) Parental influence on adolescent decisions was strong despite parents having limited knowledge about HPV vaccination and (3) Inadequacy of HPV vaccination services at the hospital and in the schools. CONCLUSION: Full HPV vaccination was low among adolescent girls living with HIV. Counseling of the adolescents by community members, alongside HPV vaccination community outreaches, provided a platform for vaccination. There should be strategies to provide adequate information about HPV vaccine to health workers, parents, and the adolescents. In addition to schools, community-based initiatives, including outreaches and lay-health workers can be utilized to improve HPV vaccine uptake among girls with HIV.