Browsing by Subject "cervical cancer"

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    Open Access
    Advances in Targeting HPV Infection as Potential Alternative Prophylactic Means
    (2021-02-23) Carse, Sinead; Bergant, Martina; Schäfer, Georgia
    Infection by oncogenic human papillomavirus (HPV) is the primary cause of cervical cancer and other anogenital cancers. The majority of cervical cancer cases occur in low- and middle- income countries (LMIC). Concurrent infection with Human Immunodeficiency Virus (HIV) further increases the risk of HPV infection and exacerbates disease onset and progression. Highly effective prophylactic vaccines do exist to combat HPV infection with the most common oncogenic types, but the accessibility to these in LMIC is severely limited due to cost, difficulties in accessing the target population, cultural issues, and maintenance of a cold chain. Alternative preventive measures against HPV infection that are more accessible and affordable are therefore also needed to control cervical cancer risk. There are several efforts in identifying such alternative prophylactics which target key molecules involved in early HPV infection events. This review summarizes the current knowledge of the initial steps in HPV infection, from host cell-surface engagement to cellular trafficking of the viral genome before arrival in the nucleus. The key molecules that can be potentially targeted are highlighted, and a discussion on their applicability as alternative preventive means against HPV infection, with a focus on LMIC, is presented.
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    Design and development of a speculum-free digital cervical cancer screening device
    (2024) Hefer, Lehan; Sivarasu, Sudesh; Saidu, Rakiya
    Introduction Cervical cancer poses a significant global health challenge, particularly in low- and middle income countries (LMICs), where the disease remains a leading cause of cancer-related deaths among women. Despite the success of cytology-based screening programs in developed nations, implementing effective screening in resource-constrained environments has proven challenging. Visual Inspection with Acetic acid (VIA), a cost-effective alternative, has limitations due to subjective diagnosis, hindering large scale implementation. This research addresses the need for improved cervical cancer screening in LMICs through the design and development of a speculum-free digital screening device. Recognising the potential of digital technology to enhance VIA's diagnostic accuracy, the project aims to create a device that combines the simplicity and cost-effectiveness of VIA with digital advancements. This research aims to develop a speculum-free cervical cancer screening device that matches the diagnostic accuracy of the standard screening tool while enhancing usability. The objectives include the development of the device, verification guided by ISO 8600 standards for medical endoscopes and ISO 14971 risk assessment, and validation of the developed device's diagnostic performance and usability through a simulated clinical study. Materials and Methods The design and development of the cervical cancer screening device, the CerviScreen, used rapid prototyping and testing principles. Comprising five subsystems—housing, visualisation, liquid application, dilation, and decontamination—the subsystems were independently designed and subsequently integrated. The dilation subsystem, developed to enable speculum-free screening, simplifies the screening process and prioritises patient comfort. The device offers a less invasive screening procedure, providing real-time video images, controllable lights, and an acetic acid application system for cleaning the cervix and inducing the acetowhitening effect for diagnosis. The first verification phase tested the dilation subsystem's compliance with engineering specifications and selected the optimal dilation cup design. Subsequently, the complete device underwent verification using tests aligned with ISO 8600 standards and auxiliary tests done by predicate devices. The second verification phase assessed the risk of the device to identify and mitigate usability and functionality risks. Validation involved simulating a cervical cancer screening procedure using a female pelvic training model in a gynaecology clinic. This comparative study assessed the CerviScreen's diagnostic accuracy against the colposcope, with experienced gynaecologists conducting diagnoses, as well as the usability of the device. Ethics approval (Reference number: HREC REF 570/2023) was obtained for this validation study. Results and Analysis Five experienced gynaecologists from Groote Schuur Hospital participated in the study, averaging 14±7.01 years of experience. The CerviScreen and colposcope demonstrated a diagnostic accuracy of 80%, indicating comparable accuracy. Usability, measured by the System Usability Score (SUS), scored 83.75, indicating 'good' usability. Post-test feedback from the participants reflected positive perceptions regarding device usability and features. Conclusion The speculum-free digital cervical cancer screening device fulfilled all design requirements to complete an entire screening procedure. It was validated to have diagnostic accuracy equivalent to that of the standard device and good usability in the simulated screening environment. While the validation testing strength lay in utilising highly experienced gynaecologists, limitations arose from inaccuracies introduced by the simplified anatomy and pathology of the female pelvic model and cervices. Despite positive results and feedback, future testing on more accurate human anatomy is essential to establish the device's efficacy. Ongoing work involves refining specific design aspects based on input from the validation study.
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    High uptake of Gardasil vaccine among 9 - 12-year-old schoolgirls participating in an HPV vaccination demonstration project in KwaZulu-Natal Province
    (2013) Moodley, Indres; Mubaiwa, V; Tathiah, N; Denny, L
    Background. Cervical cancer is linked to infection of the cervix by oncogenic human papillomavirus (HPV) subtypes. The quadrivalent Gardasil vaccine (against HPV types 6, 11, 16, 18), recommended in girls 9 - 12 years of age, has been shown to be safe, immunogenic and efficacious, with minimal or no side-effects. Aim. To demonstrate the capacity of school health teams to carry out vaccinations within a school environment. Objectives. To assess the uptake of 3 doses of the vaccine, document lessons learnt and provide recommendations for a national rollout of school-based HPV vaccination for learners. Methods. Female learners (age 9 - 12 years) from 31 primary schools in Nongoma and Ceza districts (KwaZulu-Natal province, South Africa) were identified for inclusion in the vaccination programme. The 3 doses of vaccine were administered by existing school health teams. Education and training sessions were held with all stakeholders: provincial departments of health and education; school health teams; primary healthcare nurses; hospital doctors and nurses; private practitioners; school principals, teachers and governing bodies; parents; and community and traditional leaders. Results. The overall uptake of the vaccine was found to be high: 99.7%, 97.9% and 97.8% for the first, second and third doses respectively (N=963). No adverse events were attributed to the HPV vaccine. Conclusion. This project demonstrated the successful implementation of HPV vaccination among learners (ages 9 - 12 years) using school health teams.
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    Recent Developments in Human Papillomavirus (HPV) Vaccinology
    (2023-06-26) Williamson, Anna-Lise
    Human papillomavirus (HPV) is causally associated with 5% of cancers, including cancers of the cervix, penis, vulva, vagina, anus and oropharynx. The most carcinogenic HPV is HPV-16, which dominates the types causing cancer. There is also sufficient evidence that HPV types 18, 31, 33, 35, 39, 45, 51, 52, 56, 58 and 59 cause cervical cancer. The L1 protein, which, when assembled into virus-like particles, induces HPV-type-specific neutralising antibodies, forms the basis of all commercial HPV vaccines. There are six licensed prophylactic HPV vaccines: three bivalent, two quadrivalent and one nonavalent vaccine. The bivalent vaccines protect from HPV types 16 and 18, which are associated with more than 70% of cervical cancers. Prophylactic vaccination targets children before sexual debut, but there are now catch-up campaigns, which have also been shown to be beneficial in reducing HPV infection and disease. HPV vaccination of adults after treatment for cervical lesions or recurrent respiratory papillomatosis has impacted recurrence. Gender-neutral vaccination will improve herd immunity and prevent infection in men and women. HPV vaccines are immunogenic in people living with HIV, but more research is needed on the long-term impact of vaccination and to determine whether further boosters are required.
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    The role of seminal fluid in cervical squamous carcinoma progression: Impact on cell proliferation, EMT, motility and gene expression
    (2023) Mkwanazi, Nonkululeko; Katz, Arieh; Leaner Virna
    Cervical cancer is the leading cause of cancer related deaths and the second most common cancer amongst South African women. The key cause for cervical cancer development is sexual transmission and persistent infection with high-risk Human Papillomavirus (HPV). However, it takes several years from infection to cervical cancer development, suggesting that other factors contribute to the disease. Exposure of neoplastic epithelial cells to Seminal Fluid (SF) has been shown to promote cell proliferation in culture and growth of explants in mice injected with HeLa cervical adenocarcinoma cells. Since the majority of cervical cancer cases are squamous cell carcinoma, in this study, we examined the effect of SF on cancer cell proliferation, EMT, motility and gene expression using two squamous cell carcinoma cell line model systems, SiHa and Me180. This study shows that SF significantly enhanced cell proliferation in both cell lines. Using confocal microscopy and phalloidin staining, it was further shown that SF caused morphological changes and induced stress fibre formation. SF upregulated the expression of EMT transcription factors Snail, Twist and ZEB1. EMT induction was confirmed by the increase of N-cadherin and a decrease in E-cadherin protein expression. Additionally, results showed that the induction of EMT transcription factors Snail, Twist and ZEB1 by SF occurs via EP4 receptor, ERK1/2 and COX signaling pathways. To investigate the effect of SF on migration and invasion, transwell migration assays were used. SF significantly enhanced directional cell migration and invasion of SiHa and Me180 cells. Cell invasion was associated with an increase in MMP-2 and MMP-9. SF also induced proinflammatory and angiogenic gene expression in cervical squamous carcinoma cells. SF mediated induction of inflammatory and angiogenic genes was shown to be associated with AP-1 and NFkB transcription factors. A small molecule inhibitor of nuclear import, INI-43 inhibited the nuclear localization and activity of SF activated NF-kB as well as the expression of SF induced inflammatory and angiogenic genes. Employing ectocervical tissue biopsies, SF caused the upregulation of EMT transcription factors, MMPs, inflammatory and angiogenic genes. Taken together, these results suggest that SF may play a role in promoting EMT and enhances the migratory and invasive potential of cervical squamous cell carcinoma. These findings together implicate SF as a possible factor that may promote cervical cancer progression.