Browsing by Subject "HPV"
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- ItemOpen AccessClinical validation of the HPVIR high-risk HPV test on cervical samples according to the international guidelines for human papillomavirus DNA test requirements for cervical cancer screening(2019-08-22) Gustavsson, Inger; Aarnio, Riina; Myrnäs, Mattias; Hedlund-Lindberg, Julia; Taku, Ongeziwe; Meiring, Tracy; Wikström, Ingrid; Enroth, Stefan; Williamson, Anna-Lise; Olovsson, Matts; Gyllensten, UlfAbstract Background The indicating FTA card is a dry medium used for collection of cervical samples. HPVIR is a multiplex real-time PCR test that detects 12 high-risk human papillomavirus types (hrHPV) and provides single genotype information for HPV16, − 31, − 35, − 39, − 51, − 56, and − 59 and pooled type information for HPV18/45 and HPV33/52/58. The aim of this study was to evaluate whether a strategy with cervical samples collected on the FTA card and subsequently analysed with the HPVIR test complies with the criteria of the international guidelines for a clinically validated method for cervical screening. Methods We performed a non-inferiority test comparing the clinical sensitivity and specificity of the candidate test (FTA card and HPVIR) with a clinically validated reference test (Cobas® HPV test) based on liquid-based cytology (LBC) samples. Two clinical samples (LBC and FTA) were collected from 896 participants in population-based screening. For evaluation of the specificity we used 799 women without ≥ CIN2, and for clinical sensitivity we used 67 women with histologically confirmed ≥ CIN2. The reproducibility was studied by performing inter- and intra-laboratory tests of 558 additional clinical samples. Results The clinical sensitivity and specificity for samples collected on the FTA card and analysed using the HPVIR test were non-inferior to samples analysed with the Cobas® HPV test based on LBC samples (non-inferiority test score, p = 1.0 × 10− 2 and p = 1.89 × 10− 9, respectively). Adequate agreement of > 87% was seen in both the intra- and inter-laboratory comparisons. Conclusions Samples collected on the indicating FTA card and analysed with HPVIR test fulfil the requirements of the international guidelines and can therefore be used in primary cervical cancer screening.
- ItemOpen AccessExogenous Vimentin Supplementation Transiently Affects Early Steps during HPV16 Pseudovirus Infection(2021-12-10) Carse, Sinead; Lang, Dirk; Katz, Arieh A; Schäfer, GeorgiaUnderstanding and modulating the early steps in oncogenic Human Papillomavirus (HPV) infection has great cancer-preventative potential, as this virus is the etiological agent of virtually all cervical cancer cases and is associated with many other anogenital and oropharyngeal cancers. Previous work from our laboratory has identified cell-surface-expressed vimentin as a novel HPV16 pseudovirus (HPV16-PsVs)-binding molecule modulating its infectious potential. To further explore its mode of inhibiting HPV16-PsVs internalisation, we supplemented it with exogenous recombinant human vimentin and show that only the globular form of the molecule (as opposed to the filamentous form) inhibited HPV16-PsVs internalisation in vitro. Further, this inhibitory effect was only transient and not sustained over prolonged incubation times, as demonstrated in vitro and in vivo, possibly due to full-entry molecule engagement by the virions once saturation levels have been reached. The vimentin-mediated delay of HPV16-PsVs internalisation could be narrowed down to affecting multiple steps during the virus’ interaction with the host cell and was found to affect both heparan sulphate proteoglycan (HSPG) binding as well as the subsequent entry receptor complex engagement. Interestingly, decreased pseudovirus internalisation (but not infection) in the presence of vimentin was also demonstrated for oncogenic HPV types 18, 31 and 45. Together, these data demonstrate the potential of vimentin as a modulator of HPV infection which can be used as a tool to study early mechanisms in infectious internalisation. However, further refinement is needed with regard to vimentin’s stabilisation and formulation before its development as an alternative prophylactic means.
- ItemOpen AccessHigh 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, LBackground. 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.
- ItemRestrictedJuvenile onset Recurrent Respiratory Papillomatosis (JoRRP) at Red Cross War Memorial Children’s Hospital, Cape Town: A 2-year review(2019) Pretorius, Vincent; Peer, Shazia; Fagan, JohanIntroduction: Juvenile onset recurrent respiratory papillomatosis (JoRRP) is the commonest benign paediatric neoplasm. There is no curative treatment, but the condition is self-limiting. Current primary treatment is aimed at symptomatic relief, comprising of serial surgical debulking of obstructive papillomas along the respiratory tract, with voice preservation. Adjuvant therapy is indicated in severe cases. Objective: A review of children with JoRRP presenting to the ENT Department at Red Cross War Memorial Children’s Hospital (RCWMCH) over 2 years. Evaluation of the pattern of disease and factors that may contribute to disease severity were reviewed. Method: Retrospective folder review of children with histologically confirmed laryngeal papillomatosis over above the time period. Results: Twenty children were included. Nine were male, 11 were female. The median age at diagnosis was 2.4 years (11 - 109 months). Presentation at < 3 years was noted in 5/7 of the most severe cases. Nine of 20 were HPV serotyped; 5 were type 11, and 4 were type 6. Eighty percent (16/20) were HIV negative; 10% (2/20) HIV positive; and 10% (2/20) were unknown. A total of 90 surgical procedures were performed; the highest number of surgeries per child was 13. Inter-surgical time was 1 to 164 weeks (median 9 weeks). Four received Gardasil vaccination as adjuvant therapy, 3 of who showed a reduction in disease severity. Conclusion: JoRRP commonly presents around the first 3 years of life. Severe cases can be life-threatening, often with multiple hospital admissions for clearance of surgical papillomata. Severe cases presented before 3 years. Gardasil vaccination as adjuvant therapy has promise. No identifiable risk factors in our review were noted. HIV co-infection and HPV type were not risk factors for severity.
- ItemOpen AccessPlant-based vaccines against viruses(2014-12-03) Rybicki, Edward PPlant-made or “biofarmed” viral vaccines are some of the earliest products of the technology of plant molecular farming, and remain some of the brightest prospects for the success of this field. Proofs of principle and of efficacy exist for many candidate viral veterinary vaccines; the use of plant-made viral antigens and of monoclonal antibodies for therapy of animal and even human viral disease is also well established. This review explores some of the more prominent recent advances in the biofarming of viral vaccines and therapies, including the recent use of ZMapp for Ebolavirus infection, and explores some possible future applications of the technology.
- ItemOpen AccessPlant-based vaccines against viruses(2014) Rybicki, Edward PPlant-made or "biofarmed" viral vaccines are some of the earliest products of the technology of plant molecular farming, and remain some of the brightest prospects for the success of this field. Proofs of principle and of efficacy exist for many candidate viral veterinary vaccines; the use of plant-made viral antigens and of monoclonal antibodies for therapy of animal and even human viral disease is also well established. This review explores some of the more prominent recent advances in the biofarming of viral vaccines and therapies, including the recent use of ZMapp for Ebolavirus infection, and explores some possible future applications of the technology.
- ItemOpen AccessThe role of inflammation in HPV infection of the Oesophagus(BioMed Central Ltd, 2013) Schäfer, Georgia; Kabanda, Siti; van Rooyen, Beverly; Marusic, Martina Bergant; Banks, Lawrence; Parker, M IqbalBACKGROUND: Several human cancers are known to be associated with inflammation and/or viral infections. However, the influence of tumour-related inflammation on viral uptake is largely unknown. In this study we used oesophageal squamous cell carcinoma (OSCC) as a model system since this type of cancer is associated with chronic irritation, inflammation and viral infections. Although still debated, the most important viral infection seems to be with Human Papillomavirus (HPV). The present study focused on a possible correlation between inflammation, OSCC development and the influence of HPV infection. METHODS: A total of 114 OSCC biopsies and corresponding normal tissue were collected at Groote Schuur Hospital and Tygerberg Hospital, Cape Town (South Africa), that were subjected to RNA and DNA isolation. RNA samples were analysed by quantitative Light Cycler RT-PCR for the expression of selected genes involved in inflammation and infection, while conventional PCR was performed on the DNA samples to assess the presence of integrated viral DNA. Further, an in vitro infection assay using HPV pseudovirions was established to study the influence of inflammation on viral infectivity using selected cell lines. RESULTS: HPV DNA was found in about 9% of OSCC patients, comprising predominantly the oncogenic type HPV18. The inflammatory markers IL6 and IL8 as well as the potential HPV receptor ITGA6 were significantly elevated while IL12A was downregulated in the tumour tissues. However, none of these genes were expressed in a virus-dependent manner. When inflammation was mimicked with various inflammatory stimulants such as benzo-alpha-pyrene, lipopolysaccharide and peptidoglycan in oesophageal epithelial cell lines in vitro, HPV18 pseudovirion uptake was enhanced only in the benzo-alpha-pyrene treated cells. Interestingly, HPV pseudovirion infectivity was independent of the presence of the ITGA6 receptor on the surface of the tested cells. CONCLUSION: This study showed that although the carcinogen benzo-alpha-pyrene facilitated HPV pseudovirion uptake into cells in culture, HPV infectivity was independent of inflammation and seems to play only a minor role in oesophageal cancer.
- ItemOpen AccessThe prevalence of human papillomavirus infections and associated risk factors in men-who-have-sex-with-men in Cape Town, South Africa(2016) MYller, Etienne E; Rebe, Kevin; Chirwa, Tobias F; Struthers, Helen; McIntyre, James; Lewis, David AAbstract Background We investigated the prevalence of human papillomavirus (HPV) infection and associated behavioural risk factors in men-who-have-sex-with-men (MSM) attending a clinical service in Cape Town, South Africa. Methods MSM were enrolled at the Ivan Toms Centre for Men’s Health in Cape Town. A psychosocial and sexual behavioral risk questionnaire was completed for each participant and urine, oro-pharyngeal and anal swabs were collected for HPV testing using the Linear Array HPV Genotyping Test. Logistic regression analyses were performed to determine sexual risk factors associated with HPV infection at the three anatomical sites. Results The median age of all 200 participants was 32 years (IQR 26-39.5), of which 31.0 % were black, 31.5 % mixed race/coloured and 35.5 % white. The majority of the participants (73.0 %) had completed high school, 42.0 % had a tertiary level qualification and 69.0 % were employed. HPV genotypes were detected in 72.8 % [95 % CI: 65.9–79.0 %], 11.5 % [95 % CI: 7.4–16.8 %] and 15.3 % [95 % CI: 10.5–21.2 %] of anal, oro-pharyngeal and urine specimens, respectively. Prevalence of high-risk (HR)-HPV types was 57.6 % [95 % CI: 50.3–64.7 %] in anal samples, 7.5 % [95 % CI: 4.3–12.1 %] in oro-pharyngeal samples and 7.9 % [95 % CI: 4.5–12.7 %] in urine, with HPV-16 being the most common HR-HPV type detected at all sites. HPV-6/11/16/18 was detected in 40.3 % [95 % CI: 33.3–47.6 %], 4.5 % [95 % CI: 2.1–8.4 %] and 3.2 % [95 % CI: 1.2–6.8 %] of anal, oro-pharyngeal and urine samples, respectively. Multiple HPV types were more common in the anal canal of MSM while single HPV types constituted the majority of HPV infections in the oropharynx and urine. Among the 88 MSM (44.0 %) that were HIV positive, 91.8 % [95 % CI: 83.8–96.6 %] had an anal HPV infection, 81.2 % [95 % CI: 71.2–88.8 %] had anal HR-HPV and 85.9 % [95 % CI: 76.6–92.5 %] had multiple anal HPV types. Having sex with men only, engaging in group sex in lifetime, living with HIV and practising receptive anal intercourse were the only factors independently associated with having any anal HPV infection. Conclusions Anal HPV infections were common among MSM in Cape Town with the highest HPV burden among HIV co-infected MSM, men who have sex with men only and those that practiced receptive anal intercourse. Behavioural intervention strategies and the possible roll-out of HPV vaccines among all boys are urgently needed to address the high prevalence of HPV and HIV co-infections among MSM in South Africa.