Physician-collected Samples Research Articles

Evaluating different samples & techniques for hr-HPV DNA genotyping to improve the efficiency of risk profiling for oral & cervical cancers in Sikkim, India.

Background & objectives Oral and genital HPV infection in men may be a source of cervical diseases in their women partners as well as disease in themselves. This study aimed to evaluate and compare the performance of Hybrid Capture 2 (HC2) in physician-collected cervical samples and qPCR in self-collected urine and oral gargle samples of women and men, respectively, for hr-HPV infection status and genotyping. Methods One thousand and two hundred biological samples were collected from 200 women (urine, oral gargle, and cervical smear) and 200 men (urine and oral gargle) visiting a referral hospital in the remote Himalayan State of Sikkim. The extracted genomic DNA from urine and gargle samples were profiled for hr-HPV genotypes using quantitative polymerase chain reaction (qPCR) and HC2 for cervical samples. Results In women, hr-HPV was detected in 17.5 per cent of cervical samples by HC2, 25.5 per cent of urine, and 7 per cent of gargle samples by qPCR. For men, hr-HPV was detected in 8 per cent urine and 5 per cent gargle samples by qPCR. Among the HPV-positive women, 56 per cent of urine samples and 20 per cent of oral samples showed single-genotype infection, while the remaining had multiple genotypes. Amongst the HPV-positive men, 62.7 per cent of urine samples and 85.7 per cent of oral samples showed single-genotype infection while the remaining had multiple genotypes. Compared to Pap, the area under ROC was good for HC2 (AUC=0.89) and for qPCR (AUC= 0.852). Interpretation & conclusions HC2 for cervical and qPCR-based HPV DNA assay for urine and gargle sample is suitable for risk profiling for cervical cancer (CC) and oral cancer (OC) screening programmes.

The Vaginal Microbiome: Patient- versus Physician-Collected Microbial Swab: A Pilot Study.

The composition of the vaginal microbiota prior to an IVF/IVF-ICSI treatment can predict the chance of achieving a pregnancy. To improve clinical applicability and be more patient-friendly, the self-collection of vaginal samples would be preferable. However, the reliability of patient-collected samples compared to physician-collected samples remains unclear. This study compares microbiome outcomes from patient-collected versus physician-collected vaginal samples. This is a prospective pilot study consisting of two cohorts: Cohort I involved patient self-sampling of the vagina, followed by a physician-collected vaginal swab, while Cohort II involved the reversed order of collection. The interspace profiling (IS-Pro) technique was used to analyze the microbiota composition in all samples. From May 2021 to March 2022, a total of 444 samples were collected from n = 222 patients (aged 21-44 years), with Cohort I (n = 109) and Cohort II (n = 113). The vaginal microbiome composition of both cohorts was highly similar, regardless of the sampling order, with a mean cosine similarity of 0.93 (95% CI 0.91, 0.95) in Cohort I and 0.94 (95% CI 0.92, 0.96) in Cohort II. Furthermore, ANOVA analysis revealed no significant differences in bacterial species abundance between physician- and patient-collected samples, nor between first and second sample collections. The self-collection of vaginal samples can be considered comparable to physician-collected samples and indicates a more patient-friendly and convenient collection of the vaginal microbiome in an outpatient clinical setting.

Lessons learned from comparing self-collected vs. physician-collected vaginal swabs for diagnosing infections in resource-limited settings: a 24-year review

Introduction: Reproductive health is essential for women’s overall well-being, yet vaginal infections like Bacterial Vaginosis (BV), Candidiasis, and Trichomoniasis are prevalent and can lead to severe complications if left untreated. In high-income countries, healthcare systems are generally equipped to handle these infections; however, in resource-limited settings, barriers such as geographic isolation, financial constraints, and social stigmas hinder access to effective care. Self-collected vaginal swabs present a promising alternative to traditional physician-collected samples, offering potential benefits in these underserved regions. Objective: This study aims to evaluate the feasibility, diagnostic accuracy, and community acceptance of self-collected vaginal swabs compared to physician-collected samples for diagnosing bacterial vaginosis, candidiasis, and trichomoniasis in resource-limited settings, and to explore strategies for the broader implementation of this approach to improve women’s reproductive health. Methods: This narrative review synthesizes literature on the effectiveness, feasibility, and community acceptance of self-collected vaginal swabs compared to physician-collected samples for diagnosing BV, Candidiasis, and Trichomoniasis. A systematic search was conducted across PubMed, Google Scholar, and institutional repositories for studies from January 2000 to May 2024. The review encompasses various sections, including background on the significance of timely diagnosis, initiatives empowering women through self-collection, challenges and successes of these initiatives, and strategies for quality assurance and policy advocacy. Results: Self-collected vaginal swabs were found to be as accurate as physician-collected samples in diagnosing BV, Candidiasis, and Trichomoniasis. The method enhances accessibility and reduces stigma, showing potential for broader application in community health settings. Conclusion: Self-collected vaginal swabs represent a viable solution to reproductive health challenges in resource-limited settings. They offer comparable diagnostic accuracy, enhance accessibility, and can reduce cultural barriers to seeking care. Future efforts should focus on community education, technological innovations, and policy reforms to maximize the effectiveness and sustainability of this approach in improving global women’s health.

Investigating under-reported human papillomavirus genotypes in Grenadian women through self-sampling for cervical cancer screening.

To compare the adequacy, agreement, and acceptability of Papanicolaou testing (cytology) for cervical cancer screening using self-collected samples compared to physician-collected samples in Grenada in the Caribbean. Furthermore, the study identifies the human papillomavirus (HPV) genotypes present among asymptomatic women testing positive for HPV, the etiologic cause of cervical cancer. Participants were divided into two groups and two cervical samples were collected from the women in each group: a self-collected sample and a physician-collected sample. Cervical specimens were tested for cytology and HPV. HPV genotyping was performed on positive specimens. Self-collected samples were adequate and in agreement with physician-collected samples, showing no difference between the two sampling methods. Oncogenic high-risk HPV genotypes were identified in cervical samples which were positive for atypical squamous cells and low-grade squamous intraepithelial lesions. The high-risk HPV genotypes found, notably HPV 45 and 53, differed from those most commonly reported. Although the commonly reported high-risk genotypes HPV 16 and 18 were found, so were 31, 33, 35, 52, 66, 68, and 82. Using self-collection facilitated the discovery of unexpected HPV genotypes among asymptomatic women in Grenada. These findings add new information to the literature regarding cervical cancer and neoplasia screening and HPV genotypes in the Caribbean. This genotype information may impact surveillance of women with low-grade lesions, HPV vaccine selection, and possibly further vaccine research. Research regarding HPV in Caribbean pathology samples of cervical neoplasia and cancer is needed.

Human papillomavirus testing using HPV APTIMA® assay and an external cellularity control in self-collected samples.

In cervical cancer screening programs, the detection of high-risk human papillomavirus (HR-HPV)is now widely implemented on physician-collected samples and has expanded to include self-collected samples. The use of a cellularity control (CC)is needed to reduce false-negative HPV results. An external mRNA CC forthe HPV APTIMA®assay was assessed for its analytical performance and the results were compared with both cervix cytobrush samples taken by physicians and self-collected vaginal samples from 148 women. The performance of the CC was adjusted to control for the presence of cellular mRNA in the ThinPrep® and Multitest® transport media. This CC is user-friendly but implies to perform two independent assays on PANTHER®automate. Self-collected vaginal sampling gives a lower median CC results (13.2 vs. 16.9 min) but a higher risk of negative CC results (3.3 vs. 0%). The usefulness of the CC for the HR-HPVassay may be optimized by the definition of a threshold for a minimum cell number to be tested to increase confidence in HPV-negative results. The systematic use of an RNA CC increases confidence for HPV RNA assays on self-collected vaginal samples.

Validation of novel DNA methylation markers in cervical precancer and cancer.

We have recently identified, using a genome-wide approach, new methylation markers which were evaluated among various cervical intraepithelial neoplasia (CIN) grades and cervical cancer. We herein validate the methylated state of these genes in independent study populations, based on histology ascertained outcomes regardless of human papillomavirus status. CA10, DPP10, FMN2 and HAS1 (discovery set: 54 normal, 50 CIN1, 40 CIN2, 42 CIN3) were evaluated by targeted bisulfite next generation sequencing (NGS) (Illumina MiSeq platform) in 258 (training set: 100 normal, 50 CIN1, 50 CIN2, 50 CIN3, 8 cancers) and 373 (validation set: 100 normal, 57 CIN1, 61 CIN2, 53 CIN3, 102 cancers) physician-collected samples (PreservCyt). Using targeted amplification NGS data from the training set for 94 normal and eight cancer samples, we calculated for each gene the median methylation value. These were summed and normalized to compute a four-gene Marker Polygenic Score (MPS). We compared the relationship between MPS and progression from normal through CIN grades and cancer, separately in the training and validation sets, and tested its clinical performance via receiver-operating characteristic curves. MPS increased with increasing CIN grade, and accurately predicted cervical cancer in the training (area under the curve, AUC = 0.9950) and validation (AUC = 0.9337) sets, comparing normal to cancer. Using the highest threshold of 100% specificity, sensitivity for detection of cervical cancer was 67.7%; whereas reducing specificity to 95% increased sensitivity to 84.3%. Further evaluation of these biomarkers is warranted in prospective studies.

Diagnostic study of human papillomavirus DNA detection in cervical and vaginal samples using the filter paper card.

To determine the accuracy of high-risk human papillomavirus (HPV) DNA samples on filter paper in comparison to specimen transport medium (STM). This was a cross-sectional diagnostic study of 42 consecutive women who were prospectively recruited. Each had self-collected vaginal samples on filter paper, physician-collected cervical samples on filter paper, and physician-collected cervical samples in STM. HPV DNA testing was performed with a Hybrid Capture 2 system (Qiagen). Sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and agreement of filter paper methods with the standard procedure were calculated. The overall prevalence of HPV in STM was 67.5%. Detection of HPV DNA in the physician-collected cervical samples on filter paper had a sensitivity of 77.8%, a specificity of 100%, a PPV of 100%, and an NPV of 68.4%. The patient's self-sampling on filter paper had a sensitivity of 66.7%, a specificity of 100%, a PPV of 100%, and an NPV of 59.1%. The agreement between STM method and physician-collected sample on filter paper was substantial, (κ = 0.695, P < 0.001), while the agreement between STM and self-collected samples on filter paper was moderate (κ = 0.565, P < 0.001). Most patients reported that self-collection was acceptable (100%), painless (95%), and not embarrassing (95%). Filter paper, with dried self-collected vaginal samples, can be used to detect high-risk HPV with acceptable accuracy.

Cost-effectiveness of the screen-and-treat strategies using HPV test linked to thermal ablation for cervical cancer prevention in China: a modeling study

BackgroundSelf-sampling HPV test and thermal ablation are effective tools to increase screening coverage and treatment compliance for accelerating cervical cancer elimination. We assessed the cost-effectiveness of their combined strategies to inform accessible, affordable, and acceptable cervical cancer prevention strategies.MethodsWe developed a hybrid model to evaluate costs, health outcomes, and incremental cost-effectiveness ratios (ICER) of six screen-and-treat strategies combining HPV testing (self-sampling or physician-sampling), triage modalities (HPV genotyping, colposcopy or none) and thermal ablation, from a societal perspective. A designated initial cohort of 100,000 females born in 2015 was considered. Strategies with an ICER less than the Chinese gross domestic product (GDP) per capita ($10,350) were considered highly cost-effective.ResultsCompared with current strategies in China (physician-HPV with genotype or cytology triage), all screen-and-treat strategies are cost-effective and self-HPV without triage is optimal with the most incremental quality-adjusted life-years (QALYs) gained (220 to 440) in rural and urban China. Each screen-and-treat strategy based on self-collected samples is cost-saving compared with current strategies (−$818,430 to −$3540) whereas more costs are incurred using physician-collected samples compared with current physician-HPV with genotype triage (+$20,840 to +$182,840). For screen-and-treat strategies without triage, more costs (+$9404 to +$380,217) would be invested in the screening and treatment of precancerous lesions rather than the cancer treatment compared with the current screening strategies. Notably, however, more than 81.6% of HPV-positive women would be overtreated. If triaged with HPV 7 types or HPV16/18 genotypes, 79.1% or 67.2% (respectively) of HPV-positive women would be overtreated with fewer cancer cases avoided (19 cases or 69 cases).ConclusionsScreen-and-treat strategy using self-sampling HPV test linked to thermal ablation could be the most cost-effective for cervical cancer prevention in China. Additional triage with quality-assured performance could reduce overtreatment and remains highly cost-effective compared with current strategies.

Evaluation of the feasibility of human papillomavirus sponge-type self-sampling device at Japanese colposcopy clinics.

Self-sampling human papillomavirus (HPV) testing has been introduced for cervical cancer screening worldwide. In Japan, there are two types (brush and sponge) of HPV self-sampling devices. However, the recommended type for cervical cancer screening remains unclear. This study aimed to evaluate the feasibility of the HPV self-sampling device-sponge type (HSD-ST). Additionally, we aimed to examine the positive rate (sensitivity) for cervical intraepithelial neoplasia (CIN) 2 or worse using the HSD-ST. Finally, we aimed to perform a questionnaire survey regarding the usability of the HSD-ST. We included 165 women who underwent HPV testing at one of three gynecologic clinics. First, the women used the HSD-ST and completed a questionnaire regarding its usability. Subsequently, they underwent physician-sampling HPV testing and cytology. We examined the agreement rate of HPV positivity between self- and physician-sampling HPV testing. The HPV-positive rates of self- and physician-collected samples were 59.4% and 62.4%, respectively, with an overall concordance rate of 88.5% and a calculated kappa coefficient of 0.76, indicating high concordance. Moreover, the positive (sensitivity) rates for CIN2 or worse were 81.4% and 89.8% in the self- and physician-collected samples, respectively. Our findings demonstrated the feasibility and usability of the HSD-ST.

447. Improvement of Anal Pap Collection Documentation and Adequacy in PLWHIV in Infectious Diseases Clinic

Abstract Background Anal Pap smear is an essential screening tool for high-risk human papillomavirus (hrHPV)-associated anal squamous cell carcinoma (ASCC), particularly in people living with HIV (PLWHIV). Currently, there is no consensus regarding time interval or protocols for screening of anal hrHPV-associated cancer. Limited reports suggest self-collected specimens have similar cytology sensitivity compared to physician-collected samples. Methods We utilized a Quality Improvement project (QIP) to assess validity of self-collected anal swab specimens (SCS) for screening of hrHPV-related anal lesions versus physician-collected specimens (PCS) over 3 months. The protocol was implemented in an Infectious Diseases clinic by patients and physicians during routine visits. Patients learned about the QIP via educational handout and were offered self- or physician-collection. Results A total of 60 patients participated. Seventy-five percent opted for self-collection and 35/45 (78%) SCS were adequate for interpretation, compared to 10/15 (67%) PCS. Fisher exact test value was 0.49, indicating no significant difference between groups (at p&amp;lt; .05). In total, 77% of patients completed the satisfaction survey. Only 13% reported preference for physician-performed procedure, while 63% felt that a self-collection option made them more likely to complete the Pap. A limitation to this project is the Hawthorne effect, as participants were aware of the QIP and that validity of the samples depended on appropriate sample collection. There was also a relatively small sample size of self-collected specimens (n=45). Survey results Final result from surveys answered by patients that participated in the project. Conclusion Survey analysis showed increased patient satisfaction and similar adequacy of samples collected. While the project was not powered to demonstrate an increase in acceptance of anal Paps, increased satisfaction could lead to improvement over time with a simple and inexpensive workflow adjustment. Additionally, with expansion of telehealth, self-collected anal Paps may increase opportunities to complete screening at times physicians are not available. Studies with larger populations, in multiple institutions and with varying educational handouts/instruction methods may provide better data to corroborate recommendations regarding best practices for screening for ASCC. Disclosures All Authors: No reported disclosures.

Evaluating the Accuracy of Self-Collected Swabs for the Diagnosis of Mpox.

We evaluated the accuracy of patient-collected skin lesions, oropharyngeal, and rectal swabs among 50 individuals enrolled in a study of mpox viral dynamics. We found that the performance of self-collected samples was similar to that of physician-collected samples, suggesting that self-sampling is a reliable strategy for diagnosing mpox.

Comparison of cycle threshold values of the Cobas HPV test and viral loads of the BMRT HPV test in cervical cancer screening.

To validate the HPV viral loads that are reflected by the cycle threshold values of Cobas4800 as the viral load indicators by verifying the consistency of the viral loads per unit (10,000 cells) from the BMRT assay. The analysis is based on data from the Chinese Multi-Center Screening Trial (CHIMUST). The cases included in the analysis are all positive for physician-collected hrHPV on SeqHPV and/or Cobas4800 or negative for hrHPV but abnormal in cytology (≥LSIL), and some cases selected by nested case-control randomization from those negative for physician-collected hrHPV and cytology. With HPV testing results and relevant Ct values from Cobas4800 available, we tested the entire sample set with the BMRT HPV testing assay and analyzed their agreement with Cobas4800, followed by a comparison of the CtV from Cobas4800 and viral loads (lg) from BMRT by lesion grade. We included 4,485 women (mean age: 45.4 years) in the study, and 4,290 had complete data. The consistency of genotypes from Cobas4800 and BMRT for hrHPV, HPV-16, HPV-18, and 12-HPV pools was 94.9% (4070/4290, Kappa = 0.827), 99.1% (4251/4290, Kappa = 0.842), 99.6% (4,273/4,290, Kappa = 0.777), and 95.3% (4,089/4,290, Kappa = 0.821), respectively. Further analysis shows that any inconsistency between the two assays is likely among samples with comparatively lower viral loads. When analyzing per lesions of CIN2+ and CIN3+, the CtV from Cobas4800 and VL (lg) from BMRT are highly correlated inversely and follow the linear regression for HPV16 and 12-HPV pool (Pearson's or Spearman's correlation coefficient (r): In CIN3+, r HPV16 = -0.641, P < 0.001; r 12-HPVpool = -0.343, P = 0.109; In CIN2+, r HPV16 = -0.754, P < 0.001; r 12-HPVpool = -0.429, P < 0.001). The CtV from Cobas4800 and the viral loads (lg) of per unit cells from the BMRT are well correlated for lesion grading when tested on physician-collected samples. Cobas-CtV is worthy of further study for clinical application.

Human papillomavirus testing and cytology using physician-collected uterine cervical samples vs. self-collected vaginal samples and urine samples.

Human papillomavirus (HPV) testing using self-collected vaginal samples and urine samples is convenient and effective for improving the screening rate. But, to serve as an alternative cervical cancer screening technique, such tests must offer sensitivity equivalent to the HPV testing of physician-collected cervical samples. To examine the effectiveness of HPV testing using self-collected samples and urine samples, we compared the results of HPV testing using these samples with those of HPV testing using physician-collected samples and cytological examinations. The study population included 300 women (age: 20-50years) with abnormal cervical cytology. The results of HPV testing using self-collected samples and urine samples and physician-collected samples and cervical cytology were compared. For all HPV types, the κ-value was 0.773 for physician- and self-collected samples and 0.575 for physician-collected and urine samples. The κ-value for HPV type 16-positive samples was 0.988 for physician- and self-collected samples and 0.896 for physician-collected and urine samples. The κ-value for HPV type 18-positive samples was 0.856 for physician- and self-collected samples and 0.831 for physician-collected and urine samples. For other HPV types, the value was 0.809 for physician- and self-collected samples and 0.617 for physician-collected and urine samples. The obtained results were consistent between physician- and self-collected samples as well as between physician-collected and urine samples. Considering that the agreement rate was particularly high for the high-risk HPV types 16 and 18, HPV testing using physician-collected samples, self-collected samples, and urine samples was equally effective for the types with high carcinogenicity.

Comparison of HPV Test Results Using Self-collected and Physician-collected Samples for 241 CIN2+ Cases at a Colposcopy Clinic

Comparison of HPV Test Results Using Self-collected and Physician-collected Samples for 241 CIN2+ Cases at a Colposcopy Clinic

The added value of digital imaging to reflex cytology for triage of high-risk human papillomavirus positive self-sampled material in cervical cancer screening: A prospective cohort study.

Cytology performed directly on hrHPV-positive self-samples (reflex cytology) is feasible and for women with abnormal cytology, an additional cytology test at the general practitioner could be omitted. The aim of this study is to assess the added value of digital imaging (ThinPrep® Imaging System) on the clinical utility of reflex cytology by reducing screening error. A secondary analysis of a prospective cohort study. One of five Dutch screening laboratories. Women tested hrHPV-positive on self-samples between December 2018 and August 2019. Self-samples were used for reflex cytology with and without digital imaging. The follow-up data (cytological and histological results within 1 year of follow-up) were obtained through the Dutch Pathology Registry (PALGA). Test performance of the reflex cytology was determined by comparing it with physician-collected follow-up results. The sensitivity for detecting abnormal cells by reflex cytology on self-samples increased significantly from 26.3% (42/160; 95% confidence interval [CI] 19.6-33.8) without digital imaging to 35.4% (56/158; 95% CI 28-43.4) with digital imaging (P < 0.05) without compromising specificity. Importantly, 41.7% of women with ≥CIN2 (35/84) and 45.6% with ≥CIN3 (26/57) were detected by reflex cytology with digital imaging on hrHPV-positive self-samples. Digital imaging is of added value to reflex cytology on hrHPV-positive self-samples with a 9% increase in sensitivity. If reflex cytology on self-samples analysed with digital imaging had been implemented in the screening programme, 35.4% of the hrHPV-positive women with abnormal cytology on additional physician-collected samples could have been referred directly for colposcopy.

Human papillomavirus genotype concordance between Anyplex II HPV28 and linear array HPV genotyping test in anogenital samples.

Anyplex II HPV-28 (HPV-28) can detect individually 28 HPV genotypes. We assessed the agreement between linear array HPV genotyping (LA-HPV) and HPV-28 for detection of 27 HPV genotypes in 410 stored anogenital samples (75 anal samples, 335 physician-collected cervical samples) collected over 5 years from 410 individuals (13 men, 397 women), including 202 HIV-seropositive individuals. HPV DNA was detected in 393 (95.9%, 95% confidence interval [CI]: 93.4-97.4) and 382 (93.2%, 95% CI: 90.3-95.3) samples with HPV-28 and LA-HPV (p = 0.13), respectively, for a good agreement of 96.3% (κ = 0.65). Of the 10503 HPV typing results, 10195 (780 positive, 9577 negative) were concordant, for an agreement of 97.1%(95% CI: 96.7-97.4) and an excellent ofκ = 0.82(95% CI: 0.80-0.84). The mean type-specific concordance for 27 genotypes was 97.0%, 95% CI: 95.8-98.5 (κ = 0.86 ± 0.07, 95% CI: 0.83-0.88). Excellent agreement was obtained individually for all high-risk genotypes (κ = 0.81-0.97) and for most other genotypes except for types 42, 44, 54, 68, and 69. The mean number of types per sample in discordant samples detected with LA-HPV (3.0, 95% CI: 2.7-3.4) was greater than in concordant samples (1.4, 95% CI: 1.3-1.5; p< 0.001). In conclusion, HPV-28 compared favorably with LA-HPV, but was more frequently positive for HPV42 and HPV68.

A novel proteomic-based screening method for ovarian cancer using cervicovaginal fluids: A window into the abdomen

ObjectiveOur objective is to develop a site-specific proteomic-based screening test for ovarian cancer(OC) using the mucus of the cervix and vagina and evaluate a potential means for home testing. MethodsCervicovaginal fluid samples were obtained from ovarian cancer and normal control patients for LC-mass spectrometry(MS) proteomic evaluation. Statistical modeling determined the protein panel with the highest penetrance across ovarian cancer samples. A subcohort of patients consented to provide self-collected vaginal samples at home with questionnaire on feasibility. Cohen's kappa methodology was utilized to determine agreement between physician-collected and patient-collected samples. ResultsA total of 83 consecutive patient samples were collected prospectively (33 ovarian cancer & 50 controls). Thirty patients consented for self-collection. Using LC-MS, 30 peptides demonstrated independent statistical significance for detecting ovarian cancer. Using statistical modeling, the protein panel that determined the best predictor for detecting OC formed a “fingerprint” consisting of 5 proteins: serine proteinase inhibitor A1; periplakin; profilin1; apolipoprotein A1; and thymosin beta4-like protein. These peptides demonstrated a significant increase probability of detecting ovarian cancer with the ROC curve having an AUC of 0.86 (p = 0.00001). Physician-collected and patient-collected specimens demonstrated moderate agreement with kappa average of 0.6 with upper bound of 0.75. ConclusionsUsing novel site-specific collection methods, we identified an OC “fingerprint” with adequate sensitivity and specificity to warrant further evaluation in a larger cohort. Agreement of physician-collected and patient-collected samples were encouraging and could improve access to screening with a home self-collection if this screening test is validated in future studies.

Comparison of different strategies for the triage to colposcopy of women tested high-risk HPV positive on self-collected cervicovaginal samples

ObjectiveTo identify the optimal strategy for the triage of women who test high-risk (hr) HPV positive on self-collected cervicovaginal samples. MethodsThis is a diagnostic accuracy sub-analysis of the GRECOSELF study, which reported on HPV-DNA testing with self-sampling in Greece. More than 13,000 women, 25–60 years old, who resided in rural areas of Greece, provided a self-collected cervicovaginal sample. Samples were tested for HPV-DNA and HPV16/18 genotyping with the cobas® HPV test (Roche® Molecular Systems, Pleasanton, CA, USA). HrHPV positive women were referred for colposcopy. Prior to colposcopy a physician-collected sample was obtained for cytology. After colposcopy/biopsy, women were classified as having cervical disease or not, and treated accordingly. ResultsOut of 1070 hrHPV positive women, 773 were subjected to colposcopy. Seventeen triage strategies, combining HPV16/18 genotyping and cytology, were investigated. The strategy referring to colposcopy women positive for HPV16 regardless of the cytology report, and women positive for other hrHPVs, in case of a subsequent atypical squamous cells of undetermined significance or worse (ASCUS+) cytology report, presented optimal trade-off; sensitivity 96.36% [(95%CI: (91.41–100.0)], positive predictive value (PPV) 27.46% [95%CI: (21.16–33.76)], and number of colposcopies required to detect one case of Cervical Intraepithelial Neoplasia grade-2 or worse (CIN2+) 3.64. ConclusionsThe optimal strategy for the triage to colposcopy of hrHPV positive women, detected with the cobas® HPV test on self-collected cervicovaginal samples, is referring all HPV16 positive women directly to colposcopy, and women positive for HPV18 or other hrHPVs only after an ASCUS or worse cytology report.

Performance of vaginal self-sampling high-risk HPV genotyping as primary and combining cytology or viral load as secondary in cervical cancer screening

Objective: To evaluate the efficacy of high-risk HPV (HR-HPV) genotyping with vaginal self-sampling in primary screening and combining cytology or viral load for HR-HPV positive as secondary screening strategies. Methods: The data referring to HR-HPV genotyping of self-collected sample with mass array matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF-MS), HR-HPV viral load of physician-collected sample with hybrid capture Ⅱ (HC-Ⅱ), liquid-based cytology and histology of 8 556 women were from Shenzhen cervical cancer screening trial Ⅱ (SHENCCAST-Ⅱ) conducted between April 2009 and April 2010. The data were reanalyzed to determine the sensitivity and specificity to cervical intraepithelial neoplasia (CIN) of grade 2 or worse (CIN Ⅱ+), CIN of grade 3 or worse (CIN Ⅲ+) when HR-HPV genotyping combining with colposcopy as primary screening strategy based on varied HR-HPV subtype (strategy 1, including 5 sub-strategies: 1a: HPV 16/18 positive; 1b: HPV 16/18/58 positive; 1c: HPV 16/18/58/31/33 positive; 1d: HPV 16/18/58/31/33/52 positive; 1e: any HR-HPV positive). The data were also compared to determine the efficacy of cytology (strategy 2, including 5 sub-strategies: 2a, 2b, 2c, 2d, 2e) or HR-HPV viral load (strategy 3, including 4 sub-strategies: 3a, 3b, 3c, 3d) of physician-collected sample as a triage with HR-HPV genotyping for self-sampling HR-HPV positives. Results: (1) The HR-HPV positive rate was 13.77% (1 178/8 556) in the self-collected samples of 8 556 pregnant women. Of them,the prevalences of HPV 16/18, HPV 16/18/58, HPV 16/18/58/31/33 and HPV 16/18/58/31/33/52 were 3.16% (270/8 556), 5.14% (440/8 556), 6.66% (570/8 556) and 9.81% (839/8 556), respectively. The HR-HPV viral load ≥10 relative light units/control (RLU/CO) was 8.87%(759/ 8 556), while cytological results ≥atypical squamous cell of undetermined signification (ASCUS) were 12.05% (1 031/8 556). (2) The strategy 1e had the highest sensitivities for CIN Ⅱ+, CIN Ⅲ+ which were 92.70% and 94.33%,respectively,among 14 sub-strategies,while the lowest specificity and positive predictive value (PPV). Meanwhile,the required colposcopy referral rates were much higher than other 13 sub-strategies (13.77%). The other 4 sub-strategies of strategy 1 (1a, 1b, 1c, 1d), strategy 1a had the highest specificities for CIN Ⅱ+ and CIN Ⅲ+ (97.92%, 97.69%, respectively), while 1d had the highest sensitivities for CIN Ⅱ+ and CIN Ⅲ+ (88.41%, 92.20%, respectively). (3) Both strategies of referring self-sampling HPV 16/18 positives for immediate colposcopy followed by triage physician-collected sample cytology (≥ASCUS) or viral load (≥10 RLU/CO) for non-HPV 16/18 positives had significantly higher sensitivity and specificity for CIN Ⅱ, CIN Ⅲ+, as well as lower referral rates (strategy 2a and 3a). Additionally, based on these two secondary screening strategies, cumulatively using the other four HR-HPV (HPV 58, 31, 33 and 52) positives as triage for immediate colposcopy showed an enhanced sensitivity. Conclusions: Primary HR-HPV cervical cancer screening strategy based on self-sampling with triage of cytology (≥ASCUS) or viral load (≥10 RUL/CO) provides a good balance among sensitivity, specificity for CIN Ⅱ+ and CIN Ⅲ+ and the number of tests required, referral rates. The efficacy of HR-HPV genotyping combining cytology or viral load secondary screening strategies will have a spiral escalation when HPV 58, 31, 33, 52 are included.

The prevalence and distribution of human papillomavirus among 10,867 Chinese Han women

ObjectiveTo assess the prevalence and distribution of HPV genotypes among Chinese Han women, and to explore the risk of high-grade cervical lesions associated with individual hr-HPV genotypes.MethodsGenotyping and histopathology data from the Chinese Multi-Center Screening Trial (CHIMUST) and its pilot screening trial, from 6 regions across mainland China, were re-analyzed. The data from physician- and self-collected samples from 10,867 Chinese Han women (ages 30–69) were used to determine the prevalence and distribution of hr-HPV and to explore the risk association between hr-HPV genotypes and precancerous lesions.Results9.2% of the study population tested hr-HPV positive in physician-collected sample. The prevalence varied regionally from the lowest in Guangdong (6.3%) to the highest in Inner Mongolia (13.0%). The most prevalent genotypes found were HPV-52 (21.7%), HPV-16 (19.2%), HPV-58 (15.0%), HPV-39 (8.9%), and HPV-51 (8.2%). The overall odds ratios for CIN2+ and CIN3+ for the presence of HPV-16 was 58.6 (95% CI 39.2–87.5) and, 91.6 (95%CI 54.3–154.6), respectively and remained the highest odds ratio for CIN3+ in all 6 regions.ConclusionGeographical variation exists in the prevalence and distribution of hr-HPV in mainland China. HPV-16/52/58 were the most prevalent genotypes, and HPV-16 had the highest risk for high-grade cervical lesions.Trial registrationCHIMUST, Registration number: ChiCTR-EOC-16008456. Registered 11 May 2016.