Primary Cervical Cancer Screening Research Articles

Evaluation of the applicability of internal controls on self-collected samples for high-risk human papillomavirus is needed

BackgroundSelf-collection of cervical samples to detect high-risk human papillomavirus (hr-HPV) is a trending topic in primary cervical cancer screening. This study evaluates the applicability of a self-sampling device to routine molecular procedures for hr-HPV detection.MethodsIn a primary health care facility in Kinshasa, Congo, 187 self-collected samples (Evalyn Brush) were gathered and sent to Ghent University Hospital (UZ Ghent) and Algemeen Medisch Labo (AML) in Belgium where routine tests for hr-HPV were applied (Abbott RealTime hr-HPV and qPCR (E6/E7), respectively). Sample type effect was evaluated by comparing the internal control (IC) between the self-collected samples and routine, clinician-taken samples randomly selected from the UZ Ghent archive.ResultsIn UZ Ghent an error was encountered in 9.1% (17/187) of self-collected samples due to a lack of IC signal. The hr-HPV prevalence in the remaining 170 samples was 18,8%. Comparing IC results between the self-collected and clinician-collected groups, a significant difference (p < 0,001) was found, with higher IC signals in the clinician-collected group. In AML, an error was encountered in 17.6% (33/187) of samples, including 16/17 of the UZ Ghent. The remaining sample with IC error gave a negative result in AML. Among the 154 samples without IC error at AML, a correlation of 90% was seen between both laboratories with a 77% negativity rate.ConclusionTesting the self-collected specimens by 2 routine hr-HPV tests gave a high IC error rate (9.1–17.6%). A possible solution would be to differentiate cut-offs for IC values depending on sample type, as currently used cut-offs are set for clinician-taken samples.

P16/Ki67 dual stain triage versus cytology in primary human papillomavirus-based cervical cancer screening with limited genotyping.

The introduction of primary human papillomavirus (HPV) cervical cancer screening requires the implementation of an appropriate triage strategy that will be effective in detecting high-grade cervical disease without losing diagnostic specificity. From the 30.066 screening tests results, a total of 1086 with available high-risk human papillomavirus (HRHPV) with limited genotyping, cytology, and p16/Ki67 dual-stain were selected. Two triage strategies for primary HPV screening were analyzed retrospectively based on the study group. Performance characteristics for p16/Ki67 and cytology triage in the detection of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and grade 3 or worse (CIN3+) were calculated, detected in colposcopic biopsy. In HPV16/18-positive cases, primary HPV with p16/Ki67 triage was significantly more specific than cytology (53.1%/16.8% for CIN2+; p < 0.0001; 45.9%/17.0% for CIN3+; p < 0.0001), with yielded sensitivity (95.7%/84.8% for CIN2+; p = 0.0955; 100.0%/87.5% for CIN3+; p = 0.0832). In other HRHPV-positive cases (N16/N18), p16/Ki67 triage was also significantly higher specific (51.3%/15.3% for CIN2+; p < 0.0001; 44.5%/16.5% for CIN3+; p < 0.0001), with sensitivity (92.3%/74.4% for CIN2+; p = 0.0522; 90.9%/81.8% for CIN3+; p = 0.5637). Diagnostic predictive values were significantly higher for p16/Ki67 triage with the highest PPV in HPV16/18-positive cases for CIN2+ (45.4%; 95% confidence interval [CI]: 35.2-55.8; p < 0.0001) and very high NPV in all HPV-positive cases regardless of detected genotype (96.3%-100.0%). The risk (1-NPV) for CIN3+ in HRHPV16/18-positive/p16/Ki67-negative women was 0.0%. Superior diagnostic performance compared to cytology for detecting cervical cancer precursors indicates that p16/Ki67 dual-immunostain may be a highly effective tool of triage in primary HPV screening with limited HPV 16/18 genotyping in secondary cervical cancer prevention.

Triage Strategies for Non-16/Non-18 HPV-Positive Women in Primary HPV-Based Cervical Cancer Screening: p16/Ki67 Dual Stain vs. Cytology.

In the context of primary HPV cervical cancer screening, the identification of minor screening abnormalities necessitates triage tests to optimize management and mitigate overtreatment. Currently, reflex cytology and reflex p16/Ki67 dual-stain (DS) are under scrutiny for their applicability in primary HPV-based screening. However, there remains a dearth of comprehensive data for comparing their performance. Among 30,066 results from liquid-based cervical cancer screening tests, a cohort of 332 cases was meticulously selected based on available high-risk human papillomavirus (HPV) test results, limited genotyping for HPV 16 and 18, liquid-based cytology, DS, and histology outcomes from standardized colposcopy with biopsy. For cases positive for 12 other high-risk HPV genotypes, three retrospective triage approaches were analyzed. We computed the positive predictive value (PPV) for the detection of high-grade squamous intraepithelial lesions or worse (HSIL+). Both triage models employing DS (reflex cytology followed by DS and reflex DS alone in all cases) exhibited significantly higher PPV for HSIL+ compared to the strategy with reflex cytology alone (35.9%/33.3% vs. 18.8%; p < 0.0001). Additionally, these DS-based models showed higher negative predictive values (NPV) (100%/96.2% vs. 69.2%; p = 0.0024/0.0079). In the DS-inclusive models, fewer colposcopies were necessitated (103/102 vs. 154), and fewer cases of HSIL+ were overlooked (0/3 vs. 8). Our findings suggest that p16/Ki67 dual-stain, either as a standalone or combined triage test, holds promise for the effective detection of HSIL+ in patients with minor screening abnormalities in primary HPV-based cervical cancer screening.

Performance of cervical cytology and HPV testing for primary cervical cancer screening in Latin America: an analysis within the ESTAMPA study

Cervical cytology remains widely used as the initial tool in cervical cancer screening worldwide. WHO guidelines recommend replacing cytology with primary HPV testing to reach cervical cancer elimination goals. We assessed the performance of cytology and high-risk HPV testing to detect cervical precancer, cervical intraepithelial neoplasia (CIN) grade 3 or worse (CIN3+) among women aged 30-64 years participating in the ESTAMPA study. Women were screened with cytology and HPV across ESTAMPA study centres in Latin America. Screen-positives were referred to colposcopy with biopsy collection and treatment as needed. Those with no evident precancer were recalled at 18-months for a second HPV test to complete disease ascertainment. Performance indicators for cytology and HPV to detect CIN3+ were estimated. 30,606 participants with available cytology and HPV results were included in the analysis. A total of 440 histologically confirmed CIN3s and 30 cancers were diagnosed. Cytology sensitivity for CIN3+ was 48.5% (95% CI: 44.0-53.0), whereas HPV testing had a sensitivity of 98.1% (95% CI: 96.3-96.7). Specificity was 96.5% (95% CI: 96.3-96.7) using cytology and 88.7% (95% CI: 88.3-89.0) with HPV. Performance estimates varied substantially by study centre for cytology (ranging from 32.1% to 87.5% for sensitivity and from 89.2% to 99.5% for specificity) while for HPV results were more consistent across sites (96.7%-100% and 83.6-90.8%, respectively). The limited and highly variable sensitivity of cytology strongly supports transition to the more robust and reproducible HPV-based cervical screening to ensure progress towards global cervical cancer elimination targets in Latin America. IARC/WHO, UNDP, HRP/WHO, NCI and local funders.

Triage Value of Cervical Exfoliated Cell DNA Ploidy Analysis in Cervical High-Risk Human Papillomavirus-Positive Women.

This study aimed to investigate the triage value obtained in DNA ploidy analysis of cervical exfoliated cells in women with high-risk human papillomavirus (HR-HPV)-positive status in the primary screening of cervical cancer. The authors selected 3,000 HR-HPV-positive women for cervical exfoliated cell sampling and conducted DNA ploidy analysis, liquid-based cytology (LBC), colposcopy, and cervical biopsy. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of high-grade squamous intraepithelial lesion (HSIL)-positive detection between DNA ploidy analysis and LBC were compared according to histopathology diagnosis as the golden criteria, and the efficacy of predicting HSIL-positive immediate risk was evaluated. A total of 2,892 HR-HPV-positive women were enrolled in the investigation. For HSIL+ women, the DNA ploidy group showed a significantly higher sensitivity (CIN2+: 79.21% vs 65.35%, p = .022; CIN3+: 81.48% vs 70.37%, p = .013), lower specificity (CIN2+: 85.00% vs 96.59%, p < .001; CIN3+: 84.14% vs 93.41%, p < .001), and lower PPV (CIN2+: 16.23% vs 29.33%, p = .001; CIN3+: 8.92% vs 16.89%, p = .002) compared with the LBC group, whereas the NPV showed no significant difference. Compared with LBC alone in diagnosing HSIL, DNA ploidy combined with LBC showed higher specificity (CIN2+: 99.21% vs 96.59%, p = .003; CIN3+: 96.48% vs 93.41%, p < .001) and higher PPV (CIN2+: 41.35% vs 29.33%, p = .022; CIN3+: 24.81% vs 16.89%, p = .028), whereas no significant difference was observed in the sensitivity (CIN2+: 54.46% vs 65.35%, p = .063; CIN3+: 61.11% vs 70.37%, p = .221) and NPV ( p > .05). Among the HR-HPV-positive women positive for DNA ploidy, the imminent risk of CIN2+ and CIN3+ were 15.62% and 8.92%, respectively, above the threshold for the colposcopy positive rate. Among the positive cases both for DNA ploidy and the LBC result of negative for intraepithelial lesion or malignancy, the immediate risk of CIN3+ was 3.31%, below the threshold for colposcopy positive rate. Besides, for women with LBC result of ASC-US and above, the immediate risk of CIN3+ was greater than 4%. The DNA ploidy analysis can be used as an effective triage method for HR-HPV-positive women during the primary screening of cervical cancer, although it can provide higher specificity when combined with LBC and reduce the referral rate for colposcopy.

Are Canadian Women Prepared for the Transition to Primary HPV Testing in Cervical Screening? A National Survey of Knowledge, Attitudes, and Beliefs.

As Canadian provinces and territories prepare to transition to HPV-based primary screening for cervical cancer, failure to identify and address potential barriers to screening could hinder program implementation. We examined screening-eligible Canadians' attitudes towards and knowledge of cervical screening. A nationally representative sample of screening-eligible Canadians (N = 3724) completed a web-based survey in the summer of 2022. Oversampling ensured that half of the sample were underscreened for cervical cancer (>3 years since previous screening or never screened). The participants completed validated scales of cervical cancer, HPV, and HPV test knowledge and HPV test and self-sampling attitudes and beliefs. Between-group differences (underscreened vs. adequately screened) were calculated for scales and items using independent sample t-tests or chi-square tests. The underscreened participants (n = 1871) demonstrated significantly lower knowledge of cervical cancer, HPV, and the HPV test. The adequately screened participants (n = 1853) scored higher on the Confidence and Worries subscales of the HPV Test Attitudes and Beliefs Scale. The underscreened participants scored higher on the Personal Barriers and Social Norms subscales. The underscreened participants also endorsed greater Autonomy conferred by self-sampling. Our findings suggest important differential patterns of knowledge, attitudes, and beliefs between the underscreened and adequately screened Canadians. These findings highlight the need to develop targeted communication strategies and promote patient-centered, tailored approaches in cervical screening programs.

Diagnostic accuracy of extended HPV DNA genotyping and its application for risk-based cervical cancer screening strategy.

To evaluate the consistency of 14 high-risk HPVs (hr-HPVs) detection between extended HPV DNA genotyping and a well-validated partial HPV genotyping kit, and to explore the diagnostic accuracy of risk stratification strategy based on extended HPV genotyping for cervical cancer (CC) screening. Baseline data from a clinical trial of recombinant HPV 9-valent vaccine in China was analyzed. All enrolled women aged 20-45 years received cervical cytology, HPV detection by extended and partial HPV genotyping kits. Those who met the indications would further receive colposcopy. The primary endpoints were cervical intraepithelial neoplasia 2/3 or worse (CIN2+/CIN3+). A total of 8,000 women were enrolled between April 2020 and July 2020 and 83/33 cases were diagnosed as CIN2+/CIN3+. The overall agreement between the extended and partial HPV genotyping was 92.66 %. And the agreement further increased with the progression of lesions, which lead to similarly high sensitivity and negative predictive value of these kits. A stratified triage strategy of CC screening was constructed based on the immediate CIN2+/CIN3+ risk of specific HPV. Compared with the conventional HPV primary CC screening strategy, the risk-based strategy had higher specificity for CIN (CIN2+: 94.84 vs. 92.46 %, CIN3+: 96.05 vs. 91.92 %), and needed fewer colposcopies for detecting one cervical disease. Extended HPV genotyping had good agreement with a well-validated partial HPV genotyping CC primary screening kit in hr-HPV detection. Extended HPV genotyping could facilitate risk-based stratified management strategy and improve the diagnostic accuracy of primary CC screening.

The time has come to implement primary human papillomavirus screening for cervical cancer in the United States.

For the American Cancer Society (ACS), the time for primary human papillomavirus (HPV) screening implementation has unequivocally arrived for the United States, but it will require broad knowledge mobilization and addressing logistical barriers to engage the public and health providers. The ACS is using its convener role and marshalling its considerable educational and knowledge dissemination resources to advance primary HPV screening in the United States and to share best practices from countries that have done the same through the ACS Primary HPV Screening Initiative.

Clinical Performance of Cobas 6800 for the Detection of High-Risk Human Papillomavirus in Urine Samples.

Testing for high-risk human papillomavirus (HPV) as part of primary cervical cancer screening has become more common recently. The Cobas 6800, an FDA-approved cervical screening platform, detects 14 high-risk HPVs, including HPV16 and HPV18. However, this test is limited to only women, which leads to low screening rates in trans men and other non-binary people. The cervical screening of trans men and other genders, especially those lying on the female-to-male spectrum, is equally important. Furthermore, cisgender males, particularly homosexuals, are also prone to chronic HPV infections and serve as HPV carriers, transmitting it to women and other men through sexual contact. Another limitation of the test is its invasive specimen collection, which induces discomfort and genital dysphoria. Therefore, there is a need for an innovative, less invasive method that would allow the sampling process to be more comfortable. In this study, we assess the performance of the Cobas 6800 for high-risk HPV detection in urine samples spiked with HPV16, HPV18, and HPV68. The limit of detection (LOD) was calculated using a dilution series (1.25-10,000 copies/mL) over a course of three days. Furthermore, the clinical validation was performed by calculating sensitivity, specificity, and accuracy. The limit of detection ranged from 50-1000 copies/mL depending upon the genotype. Moreover, the urine test demonstrated a high clinical sensitivity of 93%, 94%, and 90% for HPV16, HPV18, and HPV68, with 100% specificity. The overall percent agreement was calculated to be 95% for both HPV16 and HPV18, and 93% for HPV68. The high concordance, reproducibility, and clinical performance of the current assay suggest that the urine-based HPV test fulfills the requirements for its use in primary cervical screening. Moreover, it has the potential to be used for mass screening to not only identify high-risk individuals, but also to monitor vaccine effectiveness.

Two self-sampling strategies for HPV primary cervical cancer screening compared with clinician-collected sampling: an economic evaluation

ObjectiveTo compare the costs and effects of three sampling strategies for human papillomavirus (HPV) primary screening.DesignCost-consequence analysis from a health system perspective using a deterministic decision tree model.SettingEngland.ParticipantsA cohort of...

Copious vaginal discharge finally diagnosed as cervical adenocarcinoma: A case report.

Copious vaginal discharge is a frequent manifestation of reproductive tract infections. However, when little effect can obtain treated as vaginitis, cervical disease should be highly suspected. A 41-year-old woman had suffering from abnormally increased vaginal discharge without any other signs of discomfort for the past 4 years. A lot of medical examinations and treatment of vaginosis were administered, resulting in unclear diagnosis and little effect. Cervical adenocarcinoma. Gynecological examination, vaginal microbiome culture, and primary cervical cancer screening were negative, and a positron emission tomography revealed an increased 18F-fluorodeoxyglucose metabolism in the local cervix. After a thorough description, the patient demanded a hysterectomy and bilateral salpingo-oophorectomy. Histopathological evaluation confirmed adenocarcinoma in situ of the uterine cervix. The correct diagnosis of symptomatic patients with increased vaginal discharge is challenging. Human papillomavirus-negative patients presenting profuse watery vaginal discharge with an abnormal signal of cervix lesion on positron emission tomography or magnetic resonance imaging should be alert to cervical adenocarcinoma. Deep-seated cervical biopsy, conization, or even hysterectomy is conducive to early diagnosis, treatment and improvement of prognosis.

Cost-Effectiveness Analysis of HPV Extended versus Partial Genotyping for Cervical Cancer Screening in Singapore.

Human papillomavirus (HPV) partial genotyping (PGT) identifies HPV16 and HPV18 individually, alongside 12 other high-risk HPV genotypes (hrHPV) collectively. HPV extended genotyping (XGT) identifies four additional hrHPV individually (HPV31, 45, 51, and 52), and reports the remaining eight in three groups (HPV33|58; 56|59|66; 35|39|68). Quality-adjusted life years (QALY), health care resource use, and costs of XGT were compared to PGT for cervical cancer screening in Singapore using DICE simulation. Women with one of the three hrHPV identified by XGT (HPV35|39|68; 56|59|66; 51), and atypical squamous cells of undetermined significance (ASCUS) on cytology, are recalled for a repeat screening in one year, instead of undergoing an immediate colposcopy with PGT. At the repeat screening, the colposcopy is performed only for persistent same-genotype infections in XGT, while with PGT, all the women with persistent HPV have a colposcopy. Screening 500,122 women, aged 30-69, with XGT, provided an incremental cost-effectiveness ratio (ICER) versus PGT of SGD 16,370/QALY, with 7130 (19.4%) fewer colposcopies, 6027 (7.0%) fewer cytology tests, 9787 (1.6%) fewer clinic consultations, yet 2446 (0.5%) more HPV tests. The XGT ICER remains well below SGD 100,000 in sensitivity analyses, (-SGD 17,736/QALY to SGD 50,474/QALY). XGT is cost-effective compared to PGT, utilizes fewer resources, and provides a risk-based approach as the primary cervical cancer screening method.

Acceptability and Preferences of Dry HR HPV Self-Sampling Mailed Kits Among Canadian Women: A Cross-Sectional Study

Human papillomavirus (HPV), a sexually transmitted disease, is identified as the source of 99.7% of cervical cancers. Screening for cervical cancer using oncogenic HPV (high-risk [HR] HPV) detection is more sensitive than traditional cytology. However, few Canadian data exist on HR HPV self-sampling. ObjectiveTo evaluate the acceptability of HR HPV self-sampling by patients, the percentage of correctly collected samples, the return rate of mailed kits, and the HPV positivity rate in a population sample based on different cervical cancer risk factors. MethodsWe conducted an observational cross-sectional study on HPV primary cervical cancer screening with self-collected cervicovaginal samples through mail service. ResultsA total of 400 kits were mailed and 310 kits were returned, making a return rate of 77.5%. Of these, 84.2% of patients were very satisfied with this method and 95.8% (297/310) of patients would choose self-sampling over cytology as their primary screening method. All patients would recommend this screening method to their friends or family members. Of the samples, 93.8% could be analyzed correctly and the HPV positivity rate was 11.7%. ConclusionIn this large and random sample, there was a strong interest in self-testing. Offering HR HPV self-sampling could increase access to cervical cancer screening. The self-screening method could also be a part of the solution to reaching under-screened populations, in particular, those who do not have a family doctor or avoid gynaecologic exams because of pain or anxiety.

Cost-effectiveness of artificial intelligence-assisted liquid-based cytology testing for cervical cancer screening in China

The 2021 World Health Organization (WHO) guidelines for cervical cancer screening recommend human papillomavirus (HPV) DNA or mRNA testing. Artificial intelligence (AI)-assisted liquid-based cytology (LBC) systems also have the potential to facilitate rapid scale-up of cervical cancer screening. We aimed to evaluate the cost-effectiveness of AI-assisted LBC testing, compared with the manual LBC and HPV-DNA testing, for primary cervical cancer screening in China. We developed a Markov model for a cohort of 100,000 women aged 30 years over a lifetime to simulate the natural history of cervical cancer progression. We evaluated the incremental cost-effectiveness ratios (ICER) of 18 screening strategies (a combination of the three screening methods with six screening frequencies) from a healthcare provider's perspective. The willingness-to-pay threshold (US$30,828) was chosen as three times the Chinese per-capita gross domestic product in 2019. Univariate and probabilistic sensitivity analyses were performed to examine the robustness of the results. Compared with no screening, all 18 screening strategies were cost-effective, with an ICER of $622-24,482 per quality-adjusted life-year (QALY) gained. If HPV testing after scaling up to population level screening costs $10.80 or more, screening once every 5 years using AI-assisted LBC would be the most cost-effective strategy with an ICER of $8790/QALY gained compared with the lower-cost non-dominated strategy on the cost-effectiveness frontier. Its probability of being cost-effective was higher (55.4%) than other strategies. Sensitivity analyses showed that the most cost-effective strategy would become AI-assisted LBC testing once every 3 years if the sensitivity (74.1%) and specificity (95.6%) of this method were both reduced by ≥10%. The most cost-effective strategy would become HPV-DNA testing once every 5 years if the cost of AI-assisted LBC was more expensive than manual LBC or if the HPV-DNA test cost is slightly reduced (from $10.8 to <$9.4). AI-assisted LBC screening once every 5 years could be more cost-effective than manually-read LBC. Using AI-assisted LBC could have comparable cost-effectiveness to HPV DNA screening, but the relative pricing of HPV DNA testing is critical in this result. National Natural Science Foundation of China, National Key R&D Program of China.

Acceptability and Preference for Human Papilloma Virus Self-Sampling among Thai Women Attending National Cancer Institute.

Cervical cancer screening is an important public health strategy to reduce cervical cancer incidence and mortality. Human papillomavirus (HPV) self-sampling is the alternative method that can potentially increase participation in cervical cancer screening. This study aimed to evaluate the acceptability of HPV self-sampling as a primary cervical cancer screening among Thai women. A cross-sectional study was conducted at National Cancer Institute, Thailand, between March and September 2021. Eligible women were invited to collect their own samples with a vaginal cotton swab for cervical screening. The data on demographics, acceptability, and preference for HPV self-sampling were collected via a self-administered questionnaire. A Likert scale was used to assess the response of self-sampling acceptability. The multivariable logistic regression determined factors that influence preference for HPV self-sampling. A total of 265 participants were recruited. Over 70% agreed that self-sampling was easy, less embarrassing, and not painful. They also felt confident in their ability to self-sample correctly and would recommend this method to a friend or relative. For their next screening round, 66.4% preferred self-sampling whereas 33.6% preferred clinician-collected samples as routine screening. The factors that influence preference for self-sampling were age, marital status, feeling less embarrassed, and confidence in performing the tests. Most of the study participants accepted HPV self-sampling. This suggests that the self-sampling method will be an additional option to increase cervical cancer screening coverage which leads to improving the effectiveness of the national program.

Using focus groups to plan culturally acceptable primary cervical cancer screening in Grenada, West Indies.

To document Grenadian women's knowledge about cervical cancer and human papillomavirus (HPV) infection, as well as their attitudes towards primary cervical cancer screening methods. In this qualitative study, we used focus groups in Grenada to gather information concerning women's knowledge about, attitudes towards and perceptions of screening for cervical cancer and general knowledge about HPV. Ten focus groups comprising 73 participants representing 5 of the 6 parishes in Grenada were conducted with women aged 19-59. Participants were asked about pelvic exams, Pap smears, HPV, reasons for seeking or avoiding cervical cancer screening and how different modalities of testing might affect their decision-making. Responses were then coded and organized into common themes. While many respondents had heard of HPV, far fewer knew about its causative role in cervical cancer, how to prevent HPV infection or testing for the high-risk HPV types that cause almost all cases of cervical cancer. Many participants were aware that cervical cancer screening was beneficial, but numerous barriers to obtaining that screening were noted, including concerns about privacy and stigma, potential discomfort, and the cost and inconvenience involved. Our findings have implications for future cervical cancer screening efforts in Grenada. Central to these efforts should be a focus on educating Grenadians about the role of HPV infection in cervical cancer and the importance of early detection through screening. In addition, addressing issues of stigma and privacy are key to eliminating cervical cancer in Grenada.

Feasibility and acceptability of self-collection of Human Papillomavirus samples for primary cervical cancer screening on the Caribbean Coast of Nicaragua: A mixed-methods study.

Cervical cancer is the primary cause of cancer death for women in Nicaragua, despite being highly preventable through vaccination against high-risk genotypes of the Human Papillomavirus (hrHPV), screening for hrHPV, and early detection of lesions. Despite technological advances designed to increase access to screening in low resource settings, barriers to increasing population-level screening coverage persist. On the Caribbean Coast of Nicaragua, only 59% of women have received one lifetime screen, compared to 78.6% of eligible women living on the Pacific and in the Interior. In concordance with the WHO's call for best practices to eliminate cervical cancer, we explored the feasibility and acceptability of self-collection of samples for hrHPV testing on the Caribbean Coast of Nicaragua through a multi-year, bi-national, community-based mixed methods study. Between 2016 and 2019, focus groups (n=25), key informant interviews (n=12) [phase I] and an environmental scan [phase II] were conducted on the Caribbean Coast of Nicaragua in partnership and collaboration with long-term research partners at the University of Virginia and community-based organizations. In spring 2020, underscreened women on the Caribbean Coast of Nicaragua were recruited and screened for hrHPV, with the choice of clinician collection or self-collection of samples. Over the course of the study, providers and potential patients expressed significant acceptability of self-collection of samples as a strategy to reduce barriers currently contributing to the low rates of screening (phases I and II). Ultimately 99.16% (n=1,767) of women chose to self-collect samples, demonstrating a high level of acceptability of self-collection in this pilot sample (phase III). Similarly, focus groups, key informant interviews, and the environmental scan (phases I and II) of resources indicated critical considerations for feasibility of implementation of both HPV primary screening and subsequently, self-collection of samples. Through phase III, we piloted hrHPV screening (n=1,782), with a 19.25% hrHPV positivity rate. Self-collection of samples for hrHPV testing demonstrated high acceptability and feasibility. Through concerted effort at the local, regional, and national levels, this project supported capacity building in reporting, monitoring, and surveilling cervical cancer screening across the continuum of cervical cancer control.

Human papillomavirus testing using existing nucleic acid testing platforms to screen women for cervical cancer: implementation studies from five sub-Saharan African countries

ObjectivesTo demonstrate acceptability and operational feasibility of introducing human papillomavirus (HPV) testing as a principal cervical cancer screening method in public health programmes in sub-Saharan Africa.Setting45 primary and secondary health...

Comparison of the performance of HPV DNA chip test and HPV PCR test in cervical cancer screening in rural China.

This study aimed to evaluate the performance of two different principles of HPV testing in primary cervical cancer screening and ASC-US triage in rural areas. 3,328 and 3,913 women were enrolled in Shanxi, China in 2017 and 2018, respectively, and screened using liquid-based cytology and different HPV tests with a 4-year follow-up. Different screening methods commonly used in clinical practice were evaluated. In the HPV PCR test cohort, the prevalence of HPV infection was 14.90%. A total of 38 cases of CIN2+ were identified at baseline, 2 of which were in the HPV-negative cohort and the rest in the HPV-positive cohort (2 = 186.85, p < 0.001). Fifty-three cases of CIN2+ were accumulated over 4 years. The HPV infection rate in the HPV DNA chip test cohort was 21.10%. A total of 26 CIN2+ cases were identified at baseline, all in the HPV-positive population (2 = 92.96, p < 0.001). 54 CIN2+ cases were cumulative over 4 years. At 4-year follow-up, HPV-negative results were significantly more protective against cervical intraepithelial neoplasia grade 2 or worse (CIN2+) than normal cytologic results at baseline. HPV screening was more sensitive and specific than cytologic screening (using ASC-US as the threshold) and performed better on the HPV DNA microarray test. In addition, compared with HPV 16/18 testing, sensitivity increases and specificity decreases when using HPV testing for cytologic ASC-US triage, regardless of which HPV test is used. In the rural areas where we implemented the study, HPV tests performed well for screening than LBC and HPV DNA chip testing performed better than HPV PCR testing in the screening cohort. Optimal screening was achieved technically when used in combination with LBC for ASC-US population triage, without thinking the feasibility for resource availability.

Validation of ASCL1 and LHX8 Methylation Analysis as Primary Cervical Cancer Screening Strategy in South African Women with Human Immunodeficiency Virus.

Compared with women who are human immunodeficiency virus (HIV) negative, women with human immunodeficiency virus (WWH) have a higher human papillomavirus (HPV) prevalence and increased cervical cancer risk, emphasizing the need for effective cervical cancer screening in this population. The present study aimed to validate methylation markers ASCL1 and LHX8 for primary screening in a South African cohort of WWH. In this post hoc analysis within the DIAgnosis in Vaccine And Cervical Cancer Screen (DiaVACCS) study, a South African observational multicenter cohort study, cervical scrape samples from 411 HIV-positive women were analyzed for hypermethylation of ASCL1 and LHX8 genes, HPV DNA, and cytology. Sensitivities, specificities, and positive and negative predictive values of primary methylation-based, HPV-based and cytology-based screening were calculated for the detection of cervical intraepithelial neoplasia of grade 3 or higher. Single markers ASCL1 and LHX8 resulted in a good performance for the detection of cervical intraepithelial neoplasia of grade 3 or higher, with sensitivities of 85.9% (95% confidence interval [CI], 78.2%-93.6%) and 89.7% (83.0%-96.5%), respectively, and specificities of 72.9% (67.3%-78.5%) and 75.0% (69.5%-80.5%). Combining markers ASCL1 and LHX8 resulted in a lower sensitivity compared with HPV testing (84.6% vs 93.6%, respectively; ratio, 0.90 [95% CI, .82-.99]) and a higher specificity (86.7% vs 78.3%; ratio 1.11 [1.02-1.20]) and reduced the referral rate from 46.8% to 33.4%. ASCL1/LHX8 methylation had a significantly higher sensitivity than cytology (threshold, high-grade intraepithelial squamous lesion or worse), (84.6% vs 74.0%, respectively; ratio, 1.16 [95% CI, 1.01-1.32]) and similar specificity (86.7% vs 91.0%; ratio, 0.95 [.90-1.003]). Our results validate the accuracy of ASCL1/LHX8 methylation analysis for primary screening in WWH, which offers a full-molecular alternative to cytology- or HPV-based screening, without the need for additional triage testing.