We review developments in molecular triaging options for women who test positive for high-risk human papillomavirus (hrHPV) on self-collected samples in the context of cervical cancer elimination. ...The World Health Organization (WHO) recommends hrHPV screening as the primary test for cervical screening due to its high sensitivity compared to other screening tests. However, when hrHPV testing is used alone for treatment decisions, a proportion of women of childbearing age receive unnecessary treatments. This provides the incentive to optimize screening regimes to minimize the risk of overtreatment in women of reproductive age. Molecular biomarkers can potentially enhance the accuracy and efficiency of screening and triage. HrHPV testing is currently the only screening test that allows triage with molecular methods using the same sample. Additionally, offering self-collected hrHPV tests to women has been reported to increase screening coverage. This creates an opportunity to focus health resources on linking screen-positive women to diagnosis and treatment. Adding an additional test to the screening algorithm (a triage test) may improve the test's positive predictive value (PPV) and offer a better balance of benefits and risks for women. Conventional triage methods like cytology and visual inspection with acetic acid (VIA) cannot be performed on self-collected samples and require additional clinic visits and subjective interpretations. Molecular triaging using methods like partial and extended genotyping, methylation tests, detection of E6/E7 proteins, and hrHPV viral load in the same sample as the hrHPV test may improve the prediction of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and invasive cancer, offering more precise, efficient, and cost-effective screening regimes. More research is needed to determine if self-collected samples are effective and cost-efficient for diverse populations and in comparison to other triage methods. The implementation of molecular triaging could improve screening accuracy and reduce the need for multiple clinical visits. These important factors play a crucial role in achieving the global goal of eliminating cervical cancer as a public health problem.
Of women with cervical cancer (CC) and HIV, 85% live in sub-Saharan Africa, where 21% of all CC cases are attributable to HIV infection. We aimed to generate internationally acceptable facility-based ...indicators to monitor and guide scale up of CC prevention and care services offered on-site or off-site by HIV clinics.
We reviewed the literature and extracted relevant indicators, grouping them into domains along the CC control continuum. From February 2021 to March 2022, we conducted a three-round, online Delphi process to reach consensus on indicators. We invited 106 experts to participate. Through an anonymous, iterative process, participants adapted the indicators to their context (round 1), then rated them for 5 criteria on a 5-point Likert-type scale (rounds 2 and 3) and then ranked their importance (round 3).
We reviewed 39 policies from 21 African countries and 7 from international organizations; 72 experts from 15 sub-Saharan Africa countries or international organizations participated in our Delphi process. Response rates were 34% in round 1, 40% in round 2, and 44% in round 3. Experts reached consensus for 17 indicators in the following domains: primary prevention (human papillomavirus prevention, n = 2), secondary prevention (screening, triage, treatment of precancerous lesions, n = 11), tertiary prevention (CC diagnosis and care, n = 2), and long-term impact of the program and linkage to HIV service (n = 2).
We recommend that HIV clinics that offer CC control services in sub-Saharan Africa implement the 17 indicators stepwise and adapt them to context to improve monitoring along the CC control cascade.
Preliminary clinical evidence suggests a detrimental effect of pathogenic variants of BRCA1 and 2 genes on fertility outcome. This meta-analysis evaluates whether women carrying BRCA mutations ...(BRCAm) have decreased ovarian reserve, in terms of Anti-Muellerian Hormone (AMH), compared to women without BRCAm (wild-type).
Systematic searches of PubMed, Medline, Scopus, Embase, Science Direct and the Cochrane Library from inception until July 2020 were conducted. All studies comparing AMH level in fertile age women, with and without BRCA pathogenic variants were considered. Sub-analyses were performed according to age, presence of breast cancer, and type of mutation.
Among 64 studies, 10 series were included. For the entire cohort, a trend of reduced AMH level were found between BRCAm carriers and women without pathogenic variants. BRCAm carriers aged 41-years or younger had lower AMH levels compared to 41-years or younger wild type women (OR: 0.73 95%CI-1.12;-0.35; p = 0.0002). This finding was confirmed for BRCA1m carriers (OR: 1 95%CI-1.96;-0.05; p = 0.004) whereas no difference was observed between BRCA2m carriers and wild type women. The same analysis on breast cancer patients with and without BRCAm achieved the same results.
Young BRCA1m carriers seem to have lower AMH level compared with wild type women and therefore a potential decreased ovarian reserve.
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•BRCAm carriers have similar AMH levels to wild-type women.•In women under 42 years old, AMH level is statistically lower in BRCA1m.•Fertility preservation counselling should be offered once BRCA pathogenic variant is diagnosed.
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Cervical cancer (CC) is the leading cause of cancer-related death among women in sub-Saharan Africa. It occurs most frequently in women living with HIV (WLHIV) and is classified as an AIDS-defining ...illness. Recent World Health Organisation (WHO) recommendations provide guidance for CC prevention policies, with specifications for WLHIV. We systematically reviewed policies for CC prevention and control in sub-Saharan countries with the highest HIV prevalence.
We included countries with an HIV prevalence ≥ 10% in 2018 and policies published between January 1
2010 and March 31
2022. We searched Medline via PubMed, the international cancer control partnership website and national governmental websites of included countries for relevant policy documents. The online document search was supplemented with expert consultation for each included country. We synthesised aspects defined in policies for HPV vaccination, sex education, condom use, tobacco control, male circumcision,cervical screening, diagnosis and treatment of cervical pre-cancerous lesions and cancer, monitoring mechanisms and cost of services to women while highlighting specificities for WLHIV.
We reviewed 33 policy documents from nine countries. All included countries had policies on CC prevention and control either as a standalone policy (77.8%), or as part of a cancer or non-communicable diseases policy (22.2%) or both (66.7%). Aspects of HPV vaccination were reported in 7 (77.8%) of the 9 countries. All countries (100%) planned to develop or review Information, Education and Communication (IEC) materials for CC prevention including condom use and tobacco control. Age at screening commencement and screening intervals for WLHIV varied across countries. The most common recommended screening and treatment methods were visual inspection with acetic acid (VIA) (88.9%), Pap smear (77.8%); cryotherapy (100%) and loop electrosurgical procedure (LEEP) (88.9%) respectively. Global indicators disaggregated by HIV status for monitoring CC programs were rarely reported. CC prevention and care policies included service costs at various stages in three countries (33.3%).
Considerable progress has been made in policy development for CC prevention and control in sub Saharan Africa. However, in countries with a high HIV burden, there is need to tailor these policies to respond to the specific needs of WLHIV. Countries may consider updating policies using the recent WHO guidelines for CC prevention, while adapting them to context realities.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The coronavirus-induced pandemic has put great pressure on health systems worldwide. Nonemergency health services, such as cancer screening, have been scaled down or withheld as a result of travel ...restrictions and resources being redirected to manage the pandemic. The present article discusses the challenges to cancer screening implementation in the pandemic environment, suggesting ways to optimize services for breast, cervical, and colorectal cancer screening.
The manuscript was drafted by a team of public health specialists with expertise in implementation and monitoring of cancer screening. A scoping review of literature revealed the lack of comprehensive guidance on continuation of cancer screening in the midst of waxing and waning of infection. The recommendations in the present article were based on the advisories issued by different health agencies and professional bodies and the authors' understanding of the best practices to maintain quality-assured cancer screening.
A well-coordinated approach is required to ensure that essential health services such as cancer management are maintained and elective services are not threatened, especially because of resource constraints. In the context of cancer screening, a few changes in invitation strategies, screening and management protocols and program governance need to be considered to fit into the new normal situation. Restoring public trust in providing efficient and safe services should be one of the key mandates for screening program reorganization. This may be a good opportunity to introduce innovations (eg, telehealth) and consider de-implementing non-evidence-based practices. It is necessary to consider increased spending on primary health care and incorporating screening services in basic health package.
The article provides guidance on reorganization of screening policies, governance, implementation, and program monitoring.
Background: The Zika virus (ZIKV) caused a large outbreak in the Americas leading to the declaration of a Public Health Emergency of International Concern in February 2016. A causal relation between ...infection and adverse congenital outcomes such as microcephaly was declared by the World Health Organization (WHO) informed by a systematic review structured according to a framework of ten dimensions of causality, based on the work of Bradford Hill. Subsequently, the evidence has continued to accumulate, which we incorporate in regular updates of the original work, rendering it a living systematic review.
Methods: We present an update of our living systematic review on the causal relation between ZIKV infection and adverse congenital outcomes and between ZIKV and GBS for four dimensions of causality: strength of association, dose-response, specificity, and consistency. We assess the evidence published between January 18, 2017 and July 1, 2019.
Results: We found that the strength of association between ZIKV infection and adverse outcomes from case-control studies differs according to whether exposure to ZIKV is assessed in the mother (OR 3.8, 95% CI: 1.7-8.7, I
2=19.8%) or the foetus/infant (OR 37.4, 95% CI: 11.0-127.1, I
2=0%). In cohort studies, the risk of congenital abnormalities was 3.5 times higher after ZIKV infection (95% CI: 0.9-13.5, I
2=0%). The strength of association between ZIKV infection and GBS was higher in studies that enrolled controls from hospital (OR: 55.8, 95% CI: 17.2-181.7, I
2=0%) than in studies that enrolled controls at random from the same community or household (OR: 2.0, 95% CI: 0.8-5.4, I
2=74.6%). In case-control studies, selection of controls from hospitals could have biased results.
Conclusions: The conclusions that ZIKV infection causes adverse congenital outcomes and GBS are reinforced with the evidence published between January 18, 2017 and July 1, 2019.
Portable devices that can be used to perform colposcopy may improve cervical cancer screening in low- and middle-income countries (LMIC) where access to colposcopy is limited. The objective of this ...study was to systematically review the diagnostic test accuracy (DTA) of these devices for the detection of cervical intraepithelial neoplasia grade 2 or higher (CIN2+).
In accordance with our protocol (Prospero CRD42018104286), we searched Embase, Medline and the Cochrane Controlled Register of Trials up to 9/2019. We included DTA studies, which investigated portable devices with moderate-to-high optical magnification (≥ 6×) for colposcopy, as described in the manual for Colposcopy and Treatment by the International Agency for Research on Cancer, with a histopathological reference standard. We used the QUADAS-2 tool to assess study quality. We examined results for sensitivity and specificity in paired forest plots, stratified by stages in the clinical pathway. We pooled estimates of test accuracy for the index test, used as an add-on to other tests, using a bivariate random-effect model.
We screened 1737 references and assessed 239 full-text articles for eligibility. Five single-gate DTA studies, including 2693 women, met the inclusion criteria. Studies evaluated two devices (Gynocular™ and Pocket) at different stages of the screening pathway. In three studies, which used the index test in an add-on capacity in 1273 women, we found a pooled sensitivity of 0.79 (95% CI 0.55-0.92) and specificity of 0.83 (95% CI 0.59-0.94). The main sources of bias were partial verification, incorporation and classification bias.
Few studies have evaluated portable devices able to perform colposcopy, so their accuracy for the detection of CIN2+ remains uncertain. Future studies should include patient-relevant and long-term outcomes, including missed cases, overtreatment, residual and recurrent disease. To meet the challenge of eliminating cervical cancer in LMIC, methods for visual assessment of the cervix need urgent redress.
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Vulvovaginal yeast infections in pregnancy are common and can cause extensive inflammation, which could contribute to adverse pregnancy outcomes. Symptomatic yeast infections are likely to cause more ...inflammation than asymptomatic. The objective of this study was to investigate associations between symptomatic and asymptomatic vulvovaginal yeast infections in pregnancy and perinatal outcomes.
We did a systematic review and searched eight databases until 01 July 2022. We included studies reporting on pregnant women with and without laboratory confirmed vulvovaginal yeast infection and preterm birth or eight other perinatal outcomes. We used random effects meta-analysis to calculate summary odds ratios (OR), 95% confidence intervals (CI) and prediction intervals for the association between yeast infection and outcomes. We described findings from studies with multivariable analyses. We assessed the risk of bias using published tools.
We screened 3909 references and included 57 studies. Only 22/57 studies reported information about participant vulvovaginal symptoms. Preterm birth was an outcome in 35/57 studies (49,161 women). In 32/35 studies with available data, the summary OR from univariable analyses was 1.01 (95% CI 0.84-1.21, I
60%, prediction interval 0.45-2.23). In analyses stratified by symptom status, we found ORs of 1.44 (95% CI 0.92-2.26) in two studies with ≥ 50% symptomatic participants, 0.84 (95% CI 0.45-1.58) in seven studies with < 50% symptomatic participants, and 1.12 (95% CI 0.94-1.35) in four studies with asymptomatic participants. In three studies with multivariable analysis, adjusted ORs were greater than one but CIs were compatible with there being no association. We did not find associations between vulvovaginal yeast infection and any secondary outcome. Most studies were at high risk of bias in at least one domain and only three studies controlled for confounding.
We did not find strong statistical evidence of an increased risk for preterm birth or eight other adverse perinatal outcomes, in pregnant women with either symptomatic or asymptomatic vulvovaginal yeast infection. The available evidence is insufficient to make recommendations about testing and treatment of vulvovaginal yeast infection in pregnancy. Future studies should assess vulvovaginal symptoms, yeast organism loads, concomitant vaginal or cervical infections, and microbiota using state-of-the-art diagnostics.
PROSPERO CRD42020197564.
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Globally, cervical cancer is the fourth leading cause of cancer-related death among women. Poor uptake of screening services contributes to the high mortality. We aimed to examine screening ...frequency, predictors of screening results, and patterns of sensitisation strategies by age group in a large, programmatic cohort.
We did a cohort study including 11 government health facilities in Lusaka, Zambia, in which we reviewed routine programmatic data collected through the Cervical Cancer Prevention Program in Zambia (CCPPZ). Participants who underwent cervical cancer screening in one of the participating study sites were considered for study inclusion if they had a screening result. Follow-up was accomplished per national guidelines. We did descriptive analyses and mixed-effects logistic regression for cervical cancer screening results allowing random effects at the individual and clinic level.
Between Jan 1, 2010, and July 31, 2019, we included 183 165 women with 204 225 results for visual inspection with acetic acid and digital cervicography (VIAC) in the analysis. Of all those screened, 21 326 (10·4%) were VIAC-positive, of whom 16 244 (76·2%) received treatment. Of 204 225 screenings, 92 838 (45·5%) were in women who were HIV-negative, 76 607 (37·5%) were in women who were HIV-positive, and 34 780 (17·0%) had an unknown HIV status. Screening frequency increased 65·7% between 2010 and 2019 with most appointments being first-time screenings (n=158 940 77·8%). Women with HIV were more likely to test VIAC-positive than women who were HIV-negative (adjusted odds ratio 3·60, 95% CI 2·14–6·08). Younger women (≤29 years) with HIV had the highest predictive probability (18·6%, 95% CI 14·2–22·9) of screening positive.
CCPPZ has effectively increased women's engagement in screening since its inception in 2006. Customised sensitisation strategies relevant to different age groups could increase uptake and adherence to screening. The high proportion of screen positivity in women younger than 20 years with HIV requires further consideration. Our data are not able to discern if women with HIV have earlier disease onset or whether this difference reflects misclassification of disease in an age group with a higher sexually transmitted infection prevalence. These data inform scale-up efforts required to achieve WHO elimination targets.
US President's Emergency Plan for AIDS Relief.
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While the Doha declaration has not been a panacea for the inequities in health care access between low- and high-income countries, its impact on the HIV/AIDS epidemic provides a compelling case study ...for today’s global health issues and the discrepancies that exist. ...efforts to replace visual inspection with acetic acid (VIA) with more accurate screening methods are urgently required and the affordability of HPV point-of-care testing warrants further evaluation. ...acceptable treatment must be linked with care. Other challenges include: (i) unwillingness to access the health facilities for vaccination or routine CC screening due to fear of COVID-19 exposure; (ii) inability to access health facilities due to transportation disruptions or overall restriction of movement due to lockdown; (iii) disruption to CC screening campaigns in communities due to risk of exposure during group meetings; (iv) disruption of school-based vaccinations due to their closure; (v) health care providers may treat patients differently if they feel unsafe due to lack of appropriate protective equipment, perpetuating further unwillingness of patients to seek medical care; (vi) inability to access the screening facility due to facility restrictions and a focus on essential health care provision only.
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