HPV-based Cervical Cancer Screening Research Articles

Clinical evaluation of primary human papillomavirus (HPV) testing with extended HPV genotyping triage for cervical cancer screening: A pooled analysis of individual patient data from nine population-based cervical cancer screening studies from China.

To assess the clinical values of extended human papillomavirus (HPV) genotyping in triage of high-risk HPV-positive women, focusing on the trade-off between cervical precancer detections and colposcopy referrals. A bivariate random-effects model was used to estimate the diagnostic accuracy of primary HPV screening with following triage strategies to detect cervical precancers: (i) partial genotyping for HPV16/18 combined with cytological testing at atypical squamous cells of undetermined significance threshold (used as the comparator), (ii) genotyping for HPV16/18/58/52, (iii) genotyping for HPV16/18/58/52/33, (iv) genotyping for HPV16/18/58/33/31, (v) genotyping for HPV16/18/58/52/33/31, and (vi) genotyping for HPV16/18/58/52/33/31/39/51. Internal risk benchmarks for clinical management were used to evaluate the risk stratification of each triage strategy. A total of 16,982 women (mean age 46.1 years, range 17-69) were included in this analysis. For CIN3+ detection, triage with HPV16/18/58/33/31 genotyping achieved lower positivity (6.85% vs. 7.35%, p = 0.001), while maintaining similar sensitivity (91.35% vs. 96.42%, p = 0.32) and specificity (94.09% vs. 93.67%, p = 0.56) compared with the comparator strategy. Similar patterns were observed for CIN2+ detection. Women with a positive HPV16/18/58/33/31 genotyping test had high enough risk for CIN3+ for colposcopy referral, while the risk for women with a negative test was below the 1-year return decision threshold according to internal benchmarks. Our findings suggested extended HPV genotyping is of potential to be used as a triage technique integrated into HPV-based cervical cancer screening, leading to reduced need for colposcopy referral while maintaining similar disease detection and efficient risk stratification.

The impact of loss to follow-up in the Dutch organised HPV-based cervical cancer screening programme.

Loss to follow-up (LTFU) within cervical screening programmes can result in missed clinically relevant lesions, potentially reducing programme effectiveness. To examine the health impact of losing women during the screening process, we determined the proportion of women LTFU per step of the Dutch hrHPV-based screening programme. We then determined the probability of being LTFU by age, screening history and sampling method (self- or clinician-sampled) using logistic regression analysis. Finally, we estimated the number of missed CIN2+/3+ lesions per LTFU moment by using the CIN-risk in women compliant with follow-up. Data from the Dutch nationwide pathology databank (Palga) was used. Women eligible for screening in 2017 and 2018 were included (N = 840,428). For clinician collected (CC) samples, the highest proportion LTFU was found following 'referral advice for colposcopy' (5.5% after indirect referral; 3.8% after direct referral). For self-sampling, the highest proportions LTFU were found following the advice for repeat cytology (13.6%) and after referral advice for colposcopy (8.2% after indirect referral; 4.3% after direct referral). Self-sampling users and women with no screening history had a higher LTFU-risk (OR: 3.87, CI: 3.55-4.23; OR: 1.39, CI: 1.20-1.61) compared to women that used CC sampling and women that have been screened before, respectively. Of all women LTFU in 2017/18, the total number of potentially missed CIN2+ was 844 (21% of women LTFU). Most lesions were missed after 'direct referral for colposcopy' (N = 462, 11.5% of women LTFU). So, this indicates a gap between the screening programme and clinical care which requires further attention, by improving monitoring of patients after referral.

Should we use risk selection tests for HPV 16 and/or 18 positive cases: Comparison of p16/Ki67 and cytology.

Major screening abnormalities in precolposcopic stage are tests results that imply direct referral to colposcopy (and/or expedited treatment) without performing additional high-grade squamous intraepithelial lesions or worse (HSIL+) risk selection testing. Currently, both clinically validated HSIL+ risk selection tests, reflex cytology and reflex p16/Ki67 dual staining (DS), are being compared for use in primaryhuman papillomavirus (HPV)-based screening to avoid possible overtreatment, but there is still no sufficient data available for their performance. Among 30 066 liquid-based cervical cancer screening tests results, a group of 332 women was selected with available high-risk types ofHPV tests results with 16/18 limited genotyping, liquid-based cytology, DS, and histology results from standardized colposcopy with biopsy. In HPV 16/18+ cases, three triage approaches were retrospectively analyzed. Predictive values for detection of HSIL+ were calculated and number of colposcopies required in each strategy. Both triage models with DS used (reflex cytology followed by DS, and reflex DS alone in all cases) had significantly higher positive predictive valuefor HSIL+ than strategy with reflex cytology alone (44.2%/45.7% vs. 28.3%; p < 0.0001). In models with DS, less colposcopies were required (95/92 vs. 152) and less colposcopies were needed per HSIL+ detection (2.26/2.19 vs. 3.54). Only oneHSIL+ case was missed in both triage models with DS incorporation. p16/Ki67 dual-stain may be an effective, alone or combined with cytology, triage test to detect HSIL+ in patients with major screening abnormalities in primary HPV-based cervical cancer screening. Performing cytology as the first triage test improves the strategy by enabling referrals to expedited treatment in selected cases.

The impact of text message reminders on cryotherapy uptake among women testing positive for HPV in western Kenya: a prospective cohort study

BackgroundMobile health (mHealth) has become an increasingly popular strategy to improve healthcare delivery and health outcomes. Communicating results and health education via text may facilitate program planning and promote better engagement in care for women undergoing human papillomavirus (HPV) screening. We sought to develop and evaluate an mHealth strategy with enhanced text messaging to improve follow-up throughout the cervical cancer screening cascade.MethodsWomen aged 25–65 participated in HPV testing in six community health campaigns (CHCs) in western Kenya as part of a single arm of a cluster-randomized trial. Women received their HPV results via text message, phone call, or home visit. Those who opted for text in the first four communities received “standard” texts. After completing the fourth CHC, we conducted two semi-structured focus group discussions with women to develop an “enhanced” text strategy, including modifying the content, number, and timing of texts, for the subsequent two communities. We compared the overall receipt of results and follow-up for treatment evaluation among women in standard and enhanced text groups.ResultsAmong 2368 women who were screened in the first four communities, 566 (23.9%) received results via text, 1170 (49.4%) via phone call, and 632 (26.7%) via home visit. In the communities where enhanced text notification was offered, 264 of the 935 screened women (28.2%) opted for text, 474 (51.2%) opted for phone call, and 192 (20.5%) for home visit. Among 555 women (16.8%) who tested HPV-positive, 257 (46.3%) accessed treatment, with no difference in treatment uptake between the standard text group (48/90, 53.3%) and the enhanced text group (22/41, 53.7%). More women in the enhanced text group had prior cervical cancer screening (25.8% vs. 18.4%; p < 0.05) and reported living with HIV (32.6% vs. 20.2%; p < 0.001) than those in the standard text group.ConclusionsModifying the content and number of texts as an enhanced text messaging strategy was not sufficient to increase follow-up in an HPV-based cervical cancer screening program in western Kenya. A one-size approach to mHealth delivery does not meet the needs of all women in this region. More comprehensive programs are needed to improve linkage to care to further reduce structural and logistical barriers to cervical cancer treatment.

Clinical use of the Onclarity test with extended HPV genotyping and phenotyping in patients with suspected squamous intraepithelial lesions.

Human papillomavirus (HPV) is the most widespread virus with oncogenic potential that infects humans and there is a need to look for the most effective screening method among the population. Understanding the role of HPV in cervical dysplasia and viruses typing increased the usage of HPV-based cervical cancer screening tests using genotyping. We aim to assess the usefulness the Onclarity Test with extended genotyping and phenotyping of HPV in detecting cervical squamous intraepithelial lesions in 695 subjects who registered for regular cervical screening or due to abnormal LBC result or positive HPV results. Incidence of positive HPV depended significantly on biopsy outcome (p < 0.001). It was the highest for patients with HSIL (92.5%), lower for patients with LSIL (57.9%) and with HPV outcome of biopsy (50.0%). The sensitivity of positive HPV for detecting HSIL was equal to 92.50% (95% CI: 79.61%-98.43%), and specificity equalled 55.26% (95% CI: 43.41-66.69%). Sensitivity of HPV positive for any of 16, 18, 31, 45, 51 or 52 genotypes but not belonging to the P1, P2 or P3 group for detecting HSIL equalled 62.50% (95% CI: 45.80-77.27%), specificity equalled 72.37% (95% CI: 60.91-82.01%). The Onclarity test is characterised by high sensitivity and specificity in detecting CIN2+ lesions. Extended genotyping enables the identification of the most common oncogenic HPV types in the population. It can be used as a basic tool for secondary prevention or together with LBC.

High-risk human papillomavirus distribution according to human immunodeficiency virus status among women with cervical cancer in Abidjan, Côte d'Ivoire, 2018 to 2020.

As human papillomavirus (HPV) immunisation and HPV-based cervical cancer (CC) screening programmes expand across sub-Saharan Africa, we investigated the potential impact of human immunodeficiency virus (HIV) status on high-risk (HR)-HPV distribution among women with CC in Côte d'Ivoire. From July 2018 to June 2020, paraffin-embedded CC specimens diagnosed in Abidjan, Côte d'Ivoire were systematically collected and tested for HR-HPV DNA. Type-specific HR-HPV prevalence was compared according to HIV status. Of the 170 CC specimens analysed (median age 52 years, interquartile range: [43.0-60.0]), 43 (25.3%) were from women living with HIV (WLHIV) with a median CD4 count of 526 [373-833] cells/mm3 and 86% were on antiretroviral therapy (ART). The overall HR-HPV prevalence was 89.4% [95% CI: 84.7-94.1]. All were single HR-HPV infections with no differences according to HIV status (P = .8). Among HR-HPV-positive CC specimens, the most prevalent HR-HPV types were HPV16 (57.2%), HPV18 (19.7%), HPV45 (8.6%) and HPV35 (4.6%), with no significant differences according to HIV status. Altogether, infection with HPV16/18 accounted for 71.1% [95% CI: 55.9-86.2] of CC cases in WLHIV vs 78.9% [95% CI: 71.3-86.5] in women without HIV (P = .3). The study confirms the major role of HPV16/18 in CC in Côte d'Ivoire and should support a regional scale-up of HPV16/18 vaccination programmes regardless of HIV status. However, vaccines targeting additional HR-HPV types, including HPV45 and HPV35, could further decrease future CC incidence in Côte d'Ivoire, both for WLHIV and women without HIV.

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.

DNA methylation as a triage marker for colposcopy referral in HPV-based cervical cancer screening: a systematic review and meta-analysis

BackgroundScreening plays a key role in secondary prevention of cervical cancer. High-risk human papillomavirus (hrHPV) testing, a highly sensitive test but with limited specificity, has become the gold standard frontline for screening programs. Thus, the importance of effective triage strategies, including DNA methylation markers, has been emphasized. Despite the potential reported in individual studies, methylation markers still require validation before being recommended for clinical practice. This systematic review and meta-analysis aimed to evaluate the performance of DNA methylation-based biomarkers for detecting high-grade intraepithelial lesions (HSIL) in hrHPV-positive women.MethodsHence, PubMed, Scopus, and Cochrane databases were searched for studies that assessed methylation in hrHPV-positive women in cervical scrapes. Histologically confirmed HSIL was used as endpoint and QUADAS-2 tool enabled assessment of study quality. A bivariate random-effect model was employed to pool the estimated sensitivity and specificity as well as positive (PPV) and negative (NPV) predictive values.ResultsTwenty-three studies were included in this meta-analysis, from which cohort and referral population-based studies corresponded to nearly 65%. Most of the women analyzed were Dutch, and CADM1, FAM19A4, MAL, and miR124-2 were the most studied genes. Pooled sensitivity and specificity were 0.68 (CI 95% 0.63–0.72) and 0.75 (CI 95% 0.71–0.80) for cervical intraepithelial neoplasia (CIN) 2+ detection, respectively. For CIN3+ detection, pooled sensitivity and specificity were 0.78 (CI 95% 0.74–0.82) and 0.74 (CI 95% 0.69–0.78), respectively. For pooled prevalence, PPV for CIN2+ and CIN3+ detection were 0.514 and 0.392, respectively. Furthermore, NPV for CIN2+ and CIN3+ detection were 0.857 and 0.938, respectively.ConclusionsThis meta-analysis confirmed the great potential of DNA methylation-based biomarkers as triage tool for hrHPV-positive women in cervical cancer screening. Standardization and improved validation are, however, required. Nevertheless, these markers might represent an excellent alternative to cytology and genotyping for colposcopy referral of hrHPV-positive women, allowing for more cost-effective screening programs.

Testing for Human Papillomaviruses in Urine, Blood, and Oral Specimens: an Update for the Laboratory.

Twelve high-risk alpha human papillomavirus (HPV) genotypes cause approximately 690,000 cancer cases annually, with cervical and oropharyngeal cancer being the two most prominent types. HPV testing is performed in laboratory settings for various applications of a clinical, epidemiological, and research nature using a range of clinical specimens collected by clinicians or by individuals (self-collected specimens). Here, we reflect on the importance and justification of using the right test for the right application and provide practical updates for laboratories either participating in or anticipating involvement in HPV testing in three specimen types, namely, urine, blood, and oral specimens, which are considered "alternative" specimens by many. In addition to clinician-collected cervical samples and self-collected cervicovaginal samples, first-void urine is emerging as a credible specimen for HPV-based cervical cancer screening, triage of HPV screen-positive women, monitoring HPV vaccine impact, and HPV testing in groups for which a less invasive sample is preferred. Detection of cell-free DNA (including HPV DNA) in blood has great promise for the early detection of HPV-attributable oropharyngeal cancer (HPV-AOC) and potentially other HPV-driven cancers and as an adjunct prognostic marker in long-term tumor surveillance, including treatment response. The moderate sensitivity of HPV testing in oral rinses or swabs at HPV-AOC diagnosis prevents its use in HPV-AOC secondary prevention but represents a promising prognostic tool in HPV-AOC tertiary prevention, where the HPV persistence in oral rinses throughout treatment may predict early HPV-AOC recurrences and/or the development of secondary HPV-AOC. The increasing sophistication of specific collection devices designed for alternative samples and the enhanced precision of novel molecular technologies are likely to support the evolution of this field and catalyze potential translation into routine practice.

The features of high-risk human papillomavirus infection in different female genital sites and impacts on HPV-based cervical cancer screening

BackgroundThe causal role of high-risk Human papillomavirus (HR-HPV) in the pathogenesis of anogenital cancers is well established. In contrast, information on HR-HPV distribution of continuous anatomic sites within the female genital tract is limited, and the impact of sample type on the clinical performance in HPV-based cervical cancer screening warrants investigation.MethodsA total of 2,646 Chinese women were enrolled in the study from May 2006 to April 2007. We analyzed the infection features by infection status and pathological diagnoses of 489 women with complete HR-HPV type and viral load data on the cervix, upper vagina, lower vagina, and perineum samples. Additionally, we assessed the clinical performance for detecting high-grade cervical intraepithelial neoplasia of grade two or worse (≥ CIN2) among these four types of samples.ResultsHR-HPV positivity rate was lower in the cervix (51.53%) and perineum (55.83%), higher in the upper (65.64%) and lower vagina (64.42%), and increased with the severity of cervical histological lesions (all P<0.001). Single infection was more dominant than multiple infections at each anatomic site of the female genital tract. The proportion of single HR-HPV infection decreased successively from the cervix (67.05%) to the perineum (50.00%) (Ptrend=0.019) in cervical intraepithelial neoplasia grade 1 (CIN1) and was higher in samples of the cervix (85.11%) and perineum (72.34%) in ≥ CIN2. In addition, the highest viral load was observed in the cervix compared to the other three sites. The overall agreement of the cervical and perineum samples was 79.35% and increased continuously from normal (76.55%) to ≥ CIN2 (91.49%). As for the detection of ≥ CIN2, the sensitivity was 100.00%, 97.87%, 95.74%, and 91.49% for the cervix, upper vagina, lower vagina, and perineum samples, respectively.ConclusionsSingle HR-HPV infection predominated throughout the female genital tract, but the viral load was lower compared to multiple HR-HPV infections. Despite the decreasing viral load from cervix to perineum, the clinical performance for detecting ≥ CIN2 of the perineum sample was comparable to that of the cervix.

PAX1 and SEPT9 methylation analyses in cervical exfoliated cells are highly efficient for detecting cervical (pre)cancer in hrHPV-positive women

Studies have investigated PAX1 and SEPT methylation were closely associated with cervical cancer. For this study, we verified the expressions of PAX1 and SEPT9 methylation in 236 hrHPV women cervical exfoliated cells by using quantitative methylation-specific PCR and we further explored their diagnostic value in cervical (pre)cancer detection. Our results identified that the methylation rates and levels of PAX1 and SEPT9 increased with cervical lesion severity. For a diagnosis of cervical (pre)cancer, the area under the curve (AUC) of PAX1 methylation was 0.77 (95% CI 0.71–0.83) and the AUC of SEPT9 methylation was 0.86 (95% CI 0.81∼0.90). Analyses of the PAX1 and SEPT9 methylation statuses alone or combined with commonly used tests can efficiently identify cervical (pre)cancer. In particular, SEPT9 methylation might serve as an effective and powerful biomarker for the diagnosis of cervical (pre)cancer and as an alternative triage test in HPV-based cervical (pre)cancer screening programs. Impact Statement What is already known on this subject? This subject showed that PAX1 and SEPT9 methylation were closely associated with cervical cancer. The methylation rates and levels of PAX1 and SEPT9 increased with cervical lesion severity and reached a peak in cervical cancer exfoliated cells. We further assessed the diagnostic performances of PAX1 and SEPT9 methylation in cervical cancer screening. In detecting cervical (pre)cancer, the sensitivity values of PAX1 and SEPT9 methylation were up to 61.18% and 82.35%, respectively, and the specificity values of PAX1 and SEPT9 methylation were up to 95.36% and 86.75%, respectively. Moreover, the ROC curve analysis showed AUC values of 0.77 for PAX1 methylation and 0.86 for SEPT9 methylation tests, which were significantly superior to other commonly used tests. These findings suggest that PAX1 and SEPT9 methylation detection may have great clinical potential in cervical cancer screening. What the results of this study add? The rates and levels of PAX1 and SEPT9 methylation increased with the severity of the cervical lesions. For a diagnosis of cervical (pre)cancer, the area under the curve (AUC) of PAX1 methylation was 0.77 (95% CI 0.71–0.83), and the sensitivity and specificity values were 61.18% and 95.36%, respectively. The AUC value of the SEPT9 methylation was 0.86 (95% CI 0.81 ∼ 0.90), and the sensitivity and specificity values were 82.35% and 86.75%, respectively. Compared with the various tests we conducted, the PAX1 methylation showed the highest specificity (95.36%), and the SEPT9 methylation demonstrated the highest accuracy(86.00%). What the implications are of these findings for clinical practice and/or further research? The methylation levels of PAX1 and SEPT9 had a certain predictive effect on the severity of cervical lesions in hrHPV-positive women. In addition, SEPT9 methylation analysis performs better than PAX1 methylation analysis and commonly used tests in cervical exfoliated cells for detecting cervical (pre)cancer in hrHPV-positive women. SEPT9 methylation analysis merits consideration as an effective and objective, alternative triage test in HPV-based cervical (pre)cancer screening programs.

HPV prevalence and genotype distribution among women in eastern China during the Covid-19 pandemic

ABSTRACT Since March 2020, the pandemic caused by SARS-CoV-2 has affected nearly all aspects of daily life. In this study, we investigated the age-stratified prevalence and genotype distribution of human papillomavirus (HPV) among females in Shandong province (eastern China) and aimed to provide guidance on HPV-based cervical cancer screening and vaccination. The distribution of HPV genotypes was analyzed using PCR-Reverse Dot Hybridization. The overall infection rate of HPV was 16.4%, which was dominated by high-risk genotypes. The most prevalent genotype was HPV16 (2.9%), followed by HPV52 (2.3%), HPV53 (1.8%), HPV58 (1.5%), and HPV51 (1.3%). Among the positive cases with HPV infection, single-genotype infection was significantly higher than that of multi-genotype infection. In subgroup analyses by age (≤25, 26–35, 36–45, 46–55, >55), HPV16, 52, and 53 were consistently the three most common hrHPV genotypes in all age groups. The infection rate of multi-genotypes in the ≤25 and >55 age groups was significantly higher than that in other age groups. A bimodal distribution of HPV infection rate was observed in different age groups. Among lrHPV genotypes, HPV6, HPV11, and HPV81 were the three most common types in the ≤25 age group, while in other age groups, HPV81, HPV42, and HPV43 are the three most common lrHPV genotypes. This study provides basic information on the distribution and genotypes of HPV in the female population in eastern China, which could improve the application of HPV diagnostic probes and vaccines.

Comparison of human papillomavirus-based cervical cancer screening strategies in Tanzania among women with and without HIV.

Cervical cancer is the most common female cancer in Eastern Africa, and the World Health Organization (WHO) recommends human papillomavirus (HPV)-based screening as a key element to eliminate the disease. In this cross-sectional study from Tanzania, we compared nine HPV-based cervical cancer screening strategies, including HPV testing at standard cut-off; HPV testing at increased viral load cut-offs; HPV testing with partial/extended genotyping, and HPV testing with visual inspection with acetic acid (VIA). We pooled data collected during 2008 to 2009 and 2015 to 2017 from 6851 women aged 25 to 65. Cervical cytology samples were HPV tested with Hybrid Capture 2, and HPV positive samples were genotyped with INNO-LiPA Extra II. Human immunodeficiency virus (HIV) testing and VIA were done according to local standards. We calculated sensitivity, specificity, positive and negative predictive value of screening strategies, with high-grade cytological lesions as reference, separately for women with and without HIV. HPV testing at standard cut-off (1.0 relative light units [RLU]) had highest sensitivity (HIV+: 97.8%; HIV-: 91.5%), but moderate specificity (HIV+: 68.1%; HIV-: 85.7%). Increasing the cut-off for HPV positivity to higher viral loads (5.0/10.0 RLU) increased specificity (HIV+: 74.2%-76.5%; HIV-: 89.5%-91.2%), with modest sensitivity reductions (HIV+: 91.3%-95.7%; HIV-: 83.5%-87.8%). Limiting test positivity to HPV types 16/18/31/33/35/45/52/58 improved specificity while maintaining high sensitivity (HIV+: 90.2%; HIV-: 81.1%). Triage with VIA and/or partial genotyping for HPV16/18 or HPV16/18/45 had low sensitivities (≤65%). In conclusion, HPV testing alone, or HPV testing with extended genotyping or increased viral load cut-offs, may improve cervical cancer screening in Sub-Saharan Africa.

Clinical Performance of the RealTime High Risk HPV Assay on Self-Collected Vaginal Samples within the VALHUDES Framework.

ABSTRACTThe VALHUDES framework (NCT03064087) was established to evaluate the clinical accuracy of HPV testing on self-samples compared with HPV testing on matched clinician-taken cervical samples. Women referred to colposcopy due to previous cervical abnormalities were recruited at five Belgian colposcopy centers. A total of 486 pairs of matched cervical samples and vaginal self-samples were included in the analysis (228 collected with Evalyn Brush and 258 with Qvintip). The dry vaginal brushes were transferred into 20 mL ThinPrep PreservCyt solution. All specimens were tested with the Abbott RealTime High Risk HPV assay (Abbott RT). Testing on vaginal and cervical specimens was considered the index and comparator tests, respectively, and colposcopy and histology as the reference standard. The clinical sensitivity for CIN2+ of Abbott RT (cutoff ≤32 cycle number [CN]) on vaginal self-samples (Evalyn Brush and Qvintip combined) was 8% lower than on the cervical clinician-collected samples (ratio = 0.92 [95% CI, 0.87 to 0.98]), while the specificity was similar (ratio = 1.04 [95% CI, 0.97 to 1.12]). Sensitivity (ratio = 0.95 [95% CI, 0.89 to 1.02]) and specificity (ratio = 1.11 [95% CI, 0.995 to 1.23]) on Evalyn Brush samples was similar to cervical, while on Qvintip samples, the sensitivity was 12% lower than cervical samples (ratio = 0.88 [95% CI, 0.78 to 0.998]) with similar specificity (0.99 [95% CI, 0.90 to 1.10]). Exploratory cutoff optimization (cutoff ≤35 CN) resulted in an improvement of the relative sensitivity (self-sampling versus clinician sampling: ratio = 0.96 [95% CI, 0.91 to 1.02]) but yielded a loss in relative specificity (ratio = 0.92 [0.85 to 1.00]). The clinical accuracy of Abbott RT differed from the self-sampling device. However, after cutoff optimization, the sensitivity on self-samples taken with either of two vaginal brushes became similar to clinician-collected samples.IMPORTANCE Self-samples are becoming a crucial part of HPV-based cervical cancer screening programs to reach nonattendee women and increase screening coverage. Therefore, the VALHUDES framework was established to validate and evaluate HPV tests and devices on self-samples. Here, in the present manuscript, we evaluated the accuracy of the RealTime High Risk HPV assay (Abbott RT) on two different vaginal devices to detect cervical intraepithelial neoplasia grade two or higher (CIN2+). The study results demonstrated that the Abbott RT assay is similarly accurate on vaginal self-samples as on matched clinician-taken cervical samples after adjusting cutoff values. Moreover, we observed that some vaginal devices perform better than others in CIN2+ detection. We also underline the necessity of standardization and validation of general workflow and sample handling procedures for vaginal self-samples.

Prevalence and genotype distribution of human papillomavirus infection among female outpatients in Northeast China: a population-based survey of 110,927 women.

Human papillomavirus (HPV) infection, especially high-risk HPV, is a major etiological factor for cervical cancer. This study aimed to investigate the distribution of human papillomavirus infection among female outpatients in Northeast China. A total of 110,927 women aged between 18 and 80years from Shengjing Hospital of China Medical University, tested with the HPV Geno-Array Test Kit (HybriBio), were enrolled in this study. The overall prevalence of HPV infection in the study population was 16.95% (18,802/110,927). A total of 21 HPV genotypes were identified and the six most prevalent ones were HPV16 (5.78%), HPV58 (2.62%), HPV52 (1.91%), HPV33 (1.55%), HPV53 (1.45%), and HPV18 (1.16%). The prevalence of single HPV was 83.58% (15,714/18802) and that of multiple HPV was 16.42% (3088/18802). HPV16, HPV58, and HPV52 were the most common types of HR-HPV infections, while CP8304, HPV11, and HPV6 were the most common types of LR-HPV infections. Among the multiple infection groups, HPV16 was the most common type of co-infection. Furthermore, the prevalence of HPV infections varied among different age groups. Age-specific prevalence of HPV exhibited two peaks in the youngest age group and in the group aged 50-60years. HPV16, 58, 52, 33, 53, and 18 were the most common types in the general female population. The prevalence of HPV infection varied among different age groups. This study provides guidance for future HPV-based cervical cancer screening tests and prophylactic HPV vaccinations in China.

A Case for Offering HPV Self-Sampling to Well-Screened Women. Comment on Lesack et al. Willingness to Self-Collect a Sample for HPV-Based Cervical Cancer Screening in a Well-Screened Cohort: HPV FOCAL Survey Results. Curr. Oncol. 2022, 29, 3860-3869.

Lesack et al. recently published a cross-sectional study that focused on human papillomavirus (HPV) self-sampling in the screened population, a population not conventionally thought of for HPV self-sampling. They found 52% of well-screened, highly educated women who participated in the Human Papillomavirus For Cervical Cancer (HPV FOCAL) screening trial in British Columbia, Canada, would be willing to self-collect an HPV sample. We published a similar study in 2021 on well-screened, highly educated women affiliated with a family medicine clinic in Edmonton, Alberta, Canada, and found that 60% of these women preferred to have the option of HPV self-sampling. Our findings reinforce Lesack et al.’s results and together provide evidence for offering HPV self-sampling as an option for the well-screened population.

Guidance for planning, designing and running a HPV-based primary cervical cancer screening clinic in sub-Saharan Africa

Cervical cancer is an important healthcare problem in sub-Saharan Africa and emphasis should be placed on implementing and strengthening capacities for screening and treating precancerous lesions. The World Health Organization’s recommendation for low- and medium-income countries to accelerate cervical cancer elimination is human papillomavirus-based primary screening followed directly by treatment or by triage with visual inspection with acetic acid then followed by treatment. To promote these approaches in a community health-care facility, a structurally and functionally dedicated cervical cancer screening and treatment clinic is required. Publications with practical details are rare in literature, imposing a challenge in such planning. In order to provide a toolkit and guidance for health professionals who plan to set up such a clinic, we herein report our experiences in the implementation and running of a cervical cancer screening and treatment clinic adapted to a district level.

Do they cope or mope? A survey of GPs’ experiences with the changes in the Norwegian Cervical Cancer Screening Programme

Objective To explore Norwegian general practitioners’ (GPs) experiences with the changes in the cervical cancer screening programme and to uncover which aspects of the programme they find most challenging. Design We conducted an electronic cross-sectional survey. Setting Norwegian GPs were invited to participate in the survey between February and September in 2020. Subjects One hundred and fifty-five of 429 invited Norwegian GPs responded. Main outcome measures Self-reported measures were used to analyse GPs experiences and beliefs related to the screening programme. Results Most GPs did not find it particularly challenging to keep up with the changes in the screening programme, regardless of whether they came from areas with HPV-based or cytology-based cervical cancer screening implemented. Challenges concerning the follow-up of patients after an abnormal test were a frequently reported issue. We did not find any differences in how often GPs were uncertain of the follow-up of an abnormal test result in areas with HPV-based compared to cytology-based screening. Conclusions The implementation of HPV-based cervical cancer screening in women 34–69 years does not seem to have affected how challenging the GPs perceive the screening programme. Key Points How Norwegian general practitioners (GPs) keep up with changes in the Norwegian Cervical Cancer Screening Programme (NCCSP) has not been assessed previously. Most GPs did not find it particularly challenging to keep up with changes in the NCCSP regardless of whether they belonged to an area of HPV-based or cytology-based screening. The follow-up of patients with an abnormal test result was one of the main challenges reported by the GPs.

Willingness to Self-Collect a Sample for HPV-Based Cervical Cancer Screening in a Well-Screened Cohort: HPV FOCAL Survey Results.

Self-collection may provide an opportunity for innovation within population-based human papillomavirus (HPV) cervical cancer screening programs by providing an alternative form of engagement for all individuals. The primary objective was to determine willingness to self-collect a vaginal sample for primary HPV screening and factors that impact willingness in individuals who participated in the Human Papillomavirus For Cervical Cancer (HPV FOCAL) screening trial, a large randomized controlled cervical screening trial. A cross-sectional online survey was distributed between 2017 and 2018 to 13,176 eligible participants exiting the FOCAL trial. Bivariate and multivariable logistic regression assessed factors that influence willingness to self-collect on 4945 respondents. Overall, 52.1% of respondents indicated willingness to self-collect an HPV sample. In multivariable analysis, the odds of willingness to self-collect were significantly higher in participants who agreed that screening with an HPV test instead of a Pap test was acceptable to them (odds ratio (OR): 1.45 (95% confidence interval (CI): 1.15, 1.82), those who indicated that collecting their own HPV sample was acceptable to them (p < 0.001), and those with higher educational ascertainment (OR: 1.31, 95% CI: 1.12, 1.54). The findings offer insight into the intentions to self-collect in those already engaged in screening, and can inform cervical cancer screening programs interested in offering alternative approaches to HPV-based screening.

Iterative Development of a Mobile Phone App to Support Community Health Volunteers During Cervical Cancer Screening in Western Kenya: Qualitative Study.

BackgroundTo achieve the World Health Organization targets for cervical cancer elimination, low- and middle-income countries will need to develop innovative strategies to provide human papillomavirus (HPV)–based screening at a population level. Although mobile health (mHealth) interventions may help realize these goals by filling gaps in electronic specimen tracking and patient education, effective implementation of mHealth interventions is dependent upon context-specific development that is acceptable and usable by the target population. Detailed feedback should be gathered at the design and development stages to yield final products that reflect the needs, desires, and capabilities of target users.ObjectiveThe aim of this study is to develop an mHealth app (mSaada) to support HPV-based screening in partnership with community health volunteers (CHVs) and program planners in western Kenya.MethodsA team of student programmers developed a prototype to meet previously identified gaps in screening: patient education, protocol support, data capture, and specimen tracking. The prototype was iteratively developed through 2 waves of in-person working sessions with quantitative (survey) and qualitative (in-depth interview) feedback. Research staff engaged key stakeholders from both urban and rural locations and with varying levels of experience in delivering screening services. During the sessions, participants completed simulation exercises and role-play activities to become familiar with the platform. Once feedback was gathered and synthesized after each wave of in-person data collection, developers implemented changes to improve mSaada functionality.ResultsA total of 18 CHVs and clinicians participated in the in-person sessions. Participants found mSaada useful, easy to use, and would meet the needs of CHVs to provide HPV-based cervical cancer screening (electronic data capture, client education resources, and specimen tracking). They provided key feedback to enhance user experience, workflow, and sustainability. Key changes included altering the appearance of the wireframes, adding translation in additional local languages, changing potentially insensitive figures, alphabetizing lengthy dropdown menus, adding clinically relevant logic checks when entering data, and incorporating the ability to make real time edits to client records. They also made recommendations for additional features that might enhance mSaada’s impact at the facility and health system levels, specifically the inclusion of a report-generating tool consistent with the Ministry of Health standards.ConclusionsUsing a process of iterative feedback with key stakeholders and rapid response from developers, we have developed a mobile app ready for pilot testing in HPV-based screening programs led by CHVs.