Enhancing Cervical Cancer Prevention in South African Women: Primary HPV mRNA Screening with Different Genotype Combinations
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SUBMITTER: Sørbye S
PROVIDER: S-EPMC10670851 | biostudies-literature | 2023 Nov
REPOSITORIES: biostudies-literature
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Project description:Background:The efficacy of cervical cancer screening programs is dependent on the participation rate. To increase participation among women not attending cervical cancer screening, self-collected samples for detection of high-risk human papillomavirus (hr-HPV) may be an option.The aims of this study were: to investigate the response rate to sending a self-collected vaginal sample for hr-HPV mRNA detection to long-term non-attendees; the compliance with follow-up among women positive for HPV in the self-sample; the prevalence of cervical dysplasia (high grade squamous intraepithelial lesion (HSIL), atypical squamous cells that cannot exclude HSIL (ASC-H) or adenocarcinoma in situ (AIS)) or cancer among the responders; as well as to explore reasons for not returning a self-sample. Methods:A vaginal self-sampling kit was sent to 6023 women aged 30-70?years who had not provided a cervical screening sample for ?7?years in the Region of Skåne, Sweden in November and December 2017. The self-sample was analyzed by Aptima HPV mRNA assay (Hologic). All vaginal self-samples returned no later than May 31, 2018 were included in the study. Follow-up of the results was registered until January 31, 2019 with a follow-up time varying between eight to 14?months. Women positive for hr-HPV mRNA were invited for a follow-up examination. This examination consisted of a cervical sample for cytological analysis and renewed Aptima HPV mRNA testing. Two hundred thirty-five women who had not returned the self-sample were randomly selected for telephone interviews, in order to explore their reasons. Results:The response rate for the self-collected vaginal hr-HPV sample was 13.2% [(797/6023), 95% CI 12.4-14.1%] and 9.9% [(79/796), 95% CI 7.9-12.2%] were positive for hr-HPV mRNA. The prevalence of severe dysplasia or cancer in the whole group of responders was 1.3% [(10/796), 95% CI 0.6-2.3%], with a cervical cancer prevalence of 0.4% [(3/796), 95% CI 0.1-1.1%]. Only 27 women participated in the telephone interviews, no particular reason for not returning self-samples was observed. Conclusions:Self-collected vaginal hr-HPV samples increased participation in the cervical cancer screening among long-term non-attendees. The prevalence of cervical cancer was almost seven times higher for long-term non-attendees than in the organized screening population.
| S-EPMC7017526 | biostudies-literature
Project description:Background. There are limited data on high-risk human papillomavirus (hr-HPV) genotypes among HIV-positive women in Africa, and little is known about their relationship with cervical cytology in these populations. Methods. We conducted a cross-sectional study among 194 HIV-positive women (143 from Tanzania, and 51 from South Africa) to evaluate HPV genotypes among HIV-positive women with normal and abnormal cytology. Cervical samples were genotyped for HPV types, and slides were evaluated for atypical squamous cell changes according to the Bethesda classification system. Results. Prevalence of high grade squamous intraepithelial dysplasia (HSIL) was 9%. Overall, more than half (56%) of women were infected with an hr-HPV type; 94% of women with HSIL (n = 16), 90% of women with LSIL (n = 35), and 42% of women within normal limits (WNL) (n = 58) tested positive for hr-HPV. Overall, the most prevalent hr-HPV subtypes were HPV16 (26%) and HPV52 (30%). Regional differences in the prevalence of HPV18 and HPV35 were found. Conclusion. Regional differences in HPV genotypes among African women warrant the need to consider different monitoring programmes for cervical preneoplasia. HPV-based screening tests for cervical preneoplasia would be highly inefficient unless coupled with cytology screening of the HPV-positive sample, especially in HIV-positive women.
| S-EPMC3394385 | biostudies-literature
Project description:BackgroundHPV16/18 detection may improve cervical cancer risk stratification and better guide which HPV-positive women warrant immediate colposcopy/biopsy. We estimated risks of cervical precancer and cancer by HPV genotype and cytology during the implementation phase of primary HPV testing in Norway.MethodsA total of 3111 women, aged 34-69 years, testing HPV-positive at baseline and undergoing cytology testing from February 2015 to April 2018 had data available for analysis. Risk estimates with 95% confidence intervals (95%CIs) of cervical intraepithelial neoplasia grade 3 or more severe (CIN3+) were estimated for cytology results and HPV genotypes (HPV16, HPV18, and other high-risk HPV).ResultsCIN3+ risks were higher for HPV16/18 than other high-risk HPV genotypes. Among women with any cytologic abnormality [atypical squamous cells of undetermined significance or worse], immediate risks were 57.8% (95%CI = 53.0-62.6%) for HPV16, 40.2% (95%CI = 32.3-49.2%) for HPV18, and 31.4% (95%CI = 28.7-34.3%) for other high-risk HPV. Among those with normal cytology, CIN3+ risks were 19.9% (95%CI = 15.0-26.1%) for HPV16 positives, 10.8% (95%CI = 5.6-20.5%) for HPV18 positives, and 5.5% (95%CI = 4.2-7.1%) for other high-risk HPV.ConclusionsThe benefits and harms of managing women based on HPV positivity and cytology results can be better balanced by inclusion of HPV genotyping in screening and choosing more conservative management for other high-risk HPV compared to HPV16/18.
| S-EPMC7250848 | biostudies-literature
Project description:ObjectiveThe objective of this analysis was to assess human papillomavirus (HPV) infection persistence and incidence 7-months post-enrollment by HPV vaccine study arm (vaccine or placebo).MethodsHIV-negative, sexually active women aged 16-24 years in the Western Cape, South Africa, were enrolled in the EVRI Trial and were randomized to receive 4-valent HPV vaccine or placebo. Cervical specimens were collected at enrollment and at the 7-month visit and were genotyped for HPV. HPV prevalence, persistence, and incidence were calculated. Prevalence ratios and odds ratios were calculated to assess factors associated with a prevalent and incident HPV infection.ResultsHPV incidence rates were marginally higher for the placebo group (n = 163) compared to the vaccine group (n = 169). A large proportion of the prevalent high-risk (HR-HPV) HPV types (49%) persisted over the 7-month period in both arms. Prevalent HR-HPV infection was significantly associated with a prevalent gonorrhea infection and detection of Herpes simplex type 2 antibodies. Incident HR-HPV infection was significantly associated with abnormal cervical cytology at enrollment and younger age.ConclusionsWomen living in geographic areas, such as southern Africa, at high-risk for HPV need to receive HPV vaccination at a very young age to maximally prevent infection and subsequent disease.
| S-EPMC4698060 | biostudies-literature
Project description:Human papillomavirus (HPV) prevalence and genotype distribution data is important for HPV vaccine monitoring. This study investigated the prevalence and distribution of HPV genotypes in cervical lesions of unvaccinated women referred to Nelson Mandela Academic Hospital Gynaecology Department due to different abnormal cervical conditions. A total of 459 women referred to the Nelson Mandela Academic Hospital Gynaecology department were recruited. When the cervical biopsy was collected for histopathology, an adjacent biopsy was provided for HPV detection. Roche Linear Array HPV genotyping assay that detects 37 HPV genotypes was used to detect HPV infection in cervical biopsies. HPV infection was detected in 84.2% (383/455) of participants. The six most dominant HPV types were HPV-16 (34.7%), followed by HPV-35 (17.4%), HPV-58 (12.1%), HPV-45 (11.6%), HPV-18 (11.4%) and HPV-52 (9.7%). HPV-35 was the third most dominant type among women with cervical intraepithelial lesion (CIN)-2 (12.6%; single infection: 5.7% and multiple infection: 6.9%), the second most dominant type among women with CIN3 (22.2%; single infection: 8.0% and multiple infection: 14.2%); and the fourth most dominant type among women with cervical cancer (12.5%; single infection: 7.1% and multiple infection: 5.4%). A proportion of 41.1% (187/455) was positive for HPV types targeted by the Cervarix®, 42.4% (193/455) by Gardasil®4, and 66.6% (303/455) by Gardasil®9. There was a statistically significant increase when the prevalence of women infected with HPV-35 only or with other HPV types other than Gardasil®9 types was included to those infected with Gardasil®9 HPV types (66.6%, 303/455 increase to 76.0%, 346/455, p = 0.002). High HPV-35 prevalence in this population, especially among women with CIN3 warrants attention since it is not included in current commercially available HPV vaccines.
| S-EPMC8906620 | biostudies-literature
Project description:PurposeThis study aimed to evaluate the effectiveness of the national human papillomavirus (HPV) vaccination program of South Korea among its entire female population, particularly among younger age groups.Materials and methodsWe first predicted the incidence of cervical cancer over the next 20 years (2021-2040) using the Nordpred package based on Møller's age-period-cohort model under several scenarios for the national HPV vaccination program. We calculated the potential impact fractions and proportional differences under the current national vaccination programs, and alternative scenarios using the no-vaccination assumption as a reference.ResultsWe estimated that the current national vaccination program would prevent 4.13% of cervical cancer cases and reduce the age-standardized incidence rate (ASR) by 8.79% in the overall population by 2036-2040. Under the alternative scenario of implementing the nine-valent vaccine, 5.13% of cervical cancer cases could be prevented and the ASR reduced by 10.93% during the same period. In another scenario, expanding the vaccination age to 9-17 years could prevent 10.19% of cervical cancer cases, with the ASR reduced by 18.57% during the same period. When restricted to ages < 40 years, the prevention effect was remarkably greater. We predict that the current national HPV program will reduce its incidence by more than 30% between 2036 and 2040 in women aged < 40 years.ConclusionThe effectiveness of the vaccination program in reducing the incidence of cervical cancer was confirmed, with a considerable impact anticipated in younger age groups.
| S-EPMC11261207 | biostudies-literature
Project description:ObjectiveA screening centre in Soweto, South Africa (SA), investigated high-risk human papillomavirus (HR-HPV), HIV, cervical cancer risk amongst women.MethodsThis cross-sectional study (June 2018-March 2019) describes screening results (Roche Linear Array HPV test and Pap smear liquid based cytology) and history of screening (known HIV status, antiretroviral therapy [ART] use, previous Pap smears). Data were stratified by age group (18-29, 30+ years), HIV status, Pap smear results and tested for statistical significance.ResultsOf 280 women, 20.4% were HIV-positive, 18.2% had abnormal Pap smears, 41.8% had HR-HPV. Of older women, 48.2% (n = 78/162) had never had a Pap smear. Of younger women, 89.0% (n = 105/118) never had a Pap smear, but had significantly more low-grade squamous intraepithelial lesions (LSIL) and other HR-HPV infection than older women (12.7%[n = 15/118] vs 4.9%[n = 8/162], p = 0.0193; and 49.2%[n = 58/118] vs 29.0%[n = 47/162], p = 0.0006; respectively). HIV-positive women had more abnormal cytology results and infection with other HR-HPV types or co-infection with other HR-HPV type(s)/HPV-16 compared to HIV-negative women (35.1%[n = 20/57] vs 13.9%[n = 31/223], p = 0.0002; 56.1%[n = 32/57] vs 32.7%[n = 73/223], p = 0.001; and 12.3%[n = 7/57] vs 4.9%[n = 11/223], p = 0.044; respectively). Of 57 HIV-positive women, 45.6% (n = 26) already knew their HIV status; of which 69.2% were on ART and 34.6% never had a Pap smear.ConclusionSouth African women have high rates of HIV, Pap smear abnormalities and HR-HPV, with low cervical cancer screening coverage. SA cervical cancer screening policy excludes (undiagnosed) HIV-positive and HIV-negative women <30 years, both populations found to have high prevalence of HR-HPV. HPV-based primary screening from 25 years could improve outcomes.
| S-EPMC8323926 | biostudies-literature
Project description:It is estimated that 5% of the global cancer burden, or approximately 690,000 cancer cases annually, is attributable to human papillomavirus (HPV). Primary prevention through prophylactic vaccination is the best option for reducing the burden of HPV-related cancers. Most high-income countries (HICs) have introduced the HPV vaccine and are routinely vaccinating adolescent boys and girls. Unfortunately, although they suffer the greatest morbidity and mortality due to HPV-related cancers, many lower- and middle-income countries (LMICs) have been unable to initiate and sustain vaccination programs. Secondary prevention in the form of screening has led to substantial declines in cervical cancer incidence in areas with established screening programs, but LMICs with absent or inadequate screening programs have high incidence rates. Meanwhile, HICs have seen incidence rates of anal and oropharyngeal cancers rise owing to the limited availability of organized screening for anal cancer and no validated screening options for oropharyngeal cancer. The implementation of screening programs for individuals at high risk of these cancers has the potential to reduce the burden of cervical cancer in LMICs, of anal and oropharyngeal cancers in HICs, and of anal cancer for highly selected HIV+ populations in LMICs. This review will discuss primary prevention of HPV-related cancers through vaccination and secondary prevention through screening of cervical, anal, and oropharyngeal cancers. Areas of concern and highlights of successes already achieved are included.
| S-EPMC10124108 | biostudies-literature
Project description:BackgroundNew Zealand (NZ) is considering transitioning from 3-yearly cervical cytology screening in women 20-69 years (current practice) to primary HPV screening. We evaluated HPV-based screening in both HPV-unvaccinated women and cohorts offered HPV vaccination in New Zealand (vaccination coverage ~50%).MethodsA complex model of HPV transmission, vaccination, cervical screening, and invasive cervical cancer was extensively validated against national population-based datasets. Sixteen potential strategies for HPV screening were considered.ResultsMost primary HPV strategies were more effective than current practice, for both unvaccinated women and cohorts offered vaccination. The optimal strategy for both groups was 5-yearly HPV screening in women aged 25-69 years with partial genotyping for HPV 16/18 and referral to colposcopy, and cytological triage of other oncogenic types. This is predicted to reduce cervical cancer incidence and mortality by a further 12-16% and to save 4-13% annually in program costs (excluding overheads). The findings are sensitive to assumptions about future adherence to initiating screening at 25 years.ConclusionPrimary HPV screening with partial genotyping would be more effective and less costly than the current cytology-based screening program, in both unvaccinated women and cohorts offered vaccination. These findings have been considered in a review of cervical screening in NZ.
| S-EPMC4871332 | biostudies-literature
Project description:ObjectiveHypermethylation of human papillomavirus (HPV) and host genes has been reported in cervical cancer. However, the degree of methylation of different HPV types relative to the severity of the cervical lesions remains controversial. Studies of the degree of methylation associated with the host gene and the HPV genome to the severity of cervical lesions are rare. We examined the association of methylation status between host genes and late gene 1 (L1) regions of HPV16, 18, 52, and 58 in cervical brushings.MethodsCervical brushings from 147 HPV-infected patients were obtained. The samples comprised normal (n=28), cervical intraepithelial neoplasia (CIN) 1 (n=45), CIN2 (n=13), and CIN3/carcinoma in situ (n=61). The methylation status of HPV and host genes was measured using bisulfite pyrosequencing and quantitative methylation-specific polymerase chain reaction (PCR).ResultsThe degree of methylation of L1 in HPV16, 18, and 52 was associated with the severity of the cervical lesion. In HPV52, C-phosphate-G (CpG) sites 6368m, 6405m, and 6443m showed significantly higher methylation in lesions ≥CIN3 (p=0.005, 0.003, and 0.026, respectively). Methylation of most HPV types except HPV52 (r<-0.1) was positively correlated with the degree of methylation of host genes including PAX1 and SOX1 (0.4≤r≤0.7). Combining HPV methylation with PAX1 methylation improved the clustering for ≥CIN2.ConclusionOur study showed that the degree of L1 methylation of HPV16, 18, and 52 but not 58 is associated with the severity of cervical lesions. The association between HPV methylation and host gene methylation suggests different responses of host cellular epigenetic machinery to different HPV genotypes.
| S-EPMC5447154 | biostudies-literature