Primary Cervical Cancer Screening Research Articles

Clinician acceptability of self-collected human papillomavirus swabs as a primary cervical cancer screening method.

To determine knowledge and acceptability of and opinions about human papillomavirus (HPV) self-screening as an alternative to Papanicolaou testing among Canadian primary care providers (PCPs: family physicians and nurse practitioners) and obstetrician-gynecologists (OB-GYNs). Descriptive, cross-sectional, anonymous, online pilot survey. Two academic teaching hospitals in downtown Toronto, Ont. Staff physicians and nurse practitioners in the Department of Family and Community Medicine and the Department of Obstetrics and Gynecology at Women's College Hospital and St Michael's Hospital. Recommended patient groups for, potential advantages and disadvantages of, and likelihood of recommending HPV self-sampling for cervical cancer screening. The overall response rate was 30.9%. More than three-quarters of survey respondents were female PCPs. Slightly more than half of clinicians had poor knowledge of HPV self-sampling. However, more than three-quarters would recommend it if there were adequate collection of cervical samples, high patient acceptability, and high sensitivity (almost 100% of respondents), followed by high specificity and cost-effectiveness (more than 80% of respondents). Primary care practitioners were more likely than OB-GYNs to agree that HPV self-sampling made screening easier and less embarrassing for patients. Although not statistically significant, OB-GYNs tended to be more concerned than PCPs were about patients failing to follow up on abnormal HPV results and missed opportunities to address other health issues. Although knowledge of HPV self-sampling for cervical screening was poor, it was generally acceptable to clinicians if certain screening test conditions were met. However, the potential for missed opportunities to visualize pathology and address other health concerns were raised. These and other clinical practice and health systems issues must be addressed before broad implementation of HPV self-sampling in Canada.

Primary screening of cervical cancer by Pap smear in women of reproductive age group.

Cancer cervix is a major health problem responsible for causing a higher mortality rate in women worldwide; the exponential increase in such cases can be reduced by early screening of women. The cytology-based cervical screening had a higher success rate in reducing the incidence of cervical cancer. The present study aimed to evaluate the use of Pap smear screening to find cytological abnormalities and precancerous lesions. Sexually active women over 21 years of age were enrolled for the study. A detailed history was taken on the preformed proforma, and all were subjected to vaginal examination. Samples for Pap smear were taken with the help of Ayre spatula and immediately spread over a marked grease-free glass slide and dipped into 95% ethyl alcohol fixative for cytological examination. Most of the abnormality of the epithelial cells found was in the age range of 31-50 years, and most of them were multiparous. 47.92% of the women had a chief complaint of vaginal discharge, an irregular menstrual cycle in 11.07%, and abdominal pain in 7.83%, while 30.41% were asymptomatic. Women found negative for intraepithelial neoplasia were 82.94%, while 13.36% had an inflammatory smear. 0.92% atypical squamous cells of undetermined significance (ASCUS), 2.78% Low-grade squamous intraepithelial lesion (LSIL) were found, no woman had High-grade squamous intraepithelial lesion (HSIL). Pap smear is a simple, cost-effective, non-invasive, and easy to perform tool for early detection of precancerous lesions, and it is evident that every woman above the age of 25-30 years must be recommended for cervical screening.

Prikaz HPV testiranja kao primarnog skrininga raka grlića materice

Cytology-based cervical cancer screening achieved undisputable success in reducing the incidence and mortality of cervical cancer in many countries of the world, especially high-income countries. However, in lowand middle-income countries substantial reductions in cervical cancer incidence rates have not been achieved, mainly due to the difficulties in realization of complex conditions for implementing high quality cytology-based cervical cancer screening programs. Most international guidelines, including the World Health Organisation (WHO) Global Strategy, now recommend high-risk human papillomavirus (hrHPV) testing as the preferred cervical screening test, for several reasons, primarily due to its sensitivity, less subjectivity in diagnosis and possibility of easier program organization and implementation. The advantages of primary hrHPV screening include higher sensitivity of technology compared to cytology based examinations, and increased specificity in populations where large proportions of women have been vaccinated against the human papillomavirus (HPV), while the high-negative predictive value enables prolongation of screening intervals to 7 to 10 years, which increases the cost effectiveness of the screening programme, when applied at population level. Also, primary hrHPV screening for cervical cancer can be carried out by self-taken samples which increases the feasibility of such cervical cancer screening programme. However, implementing primary hrHPV cervical cancer screening requires at the same time organised system of monitoring the implementation of the program, coordination and quality assurance of all processes within the implementation of cervical cancer screening.Effective hrHPV primary cervical cancer screening programme requires the triage of hrHPV positive women to maximise the detection of clinically relevant cervical lesions for further investigation. Most of the countries that introduced hrHPV primary cervical cancer screening use visual inspection with acetic acid (VIA), cytology based examination or HPV geno-typing with cytology for triage testing. The choice of triage strategy depends on various factors, including availability of resources, effectiveness and cost of procedures to recall women for triage testing as well as the capacity and quality of existing health services to deliver the triage tests. Implementation of self-sampling also requires a number of issues to be addressed, including communication to motivate participation and to inform women about the self-sampling procedure, delivery of the self-sampling kits and return of the samples to the laboratories, laboratory procedures, communication of results, recalling screen-positive women for further examination and triage and motivating them to attend for follow-up and treatment. Finally, the introduction primary screening for HPV on the mucous membrane of the cervix should be accompanied by awareness-raising programs to improve the information and knowledge of women and the entire population about the importance of the cervical cancer screening, which would improve the results of population based cervical cancer screening programs and increase the women's participation.

Effectiveness and feasibility of HPV self-sampling for coverage of cervical cancer screening on internet-based

Objectives: To assess self-sampling HPV testing combining with the internet may serve as a primary cervical cancer screening method in low-resource settings, and to establish an internet self-sampling cervical cancer screening-management model. Methods: 20,136 women aged 30~59 years with vaginal self-sampling HPV testing as primary screening on internet-based was performed in 13 provinces, municipalities of China. The women who participated in the screening registered on the screening website. A questionnaire was investigated the acceptance of self-sampling after self-sampling. Results: Among 20103 women with qualified samples, 35.81% of them was remote areas, 37.69% of them was never-screened, 59.96% of them under-screened, 18.54% with a primary school education or below and overall high-risk HPV prevalence was 13.86%. In 8136 respondents, 95.97% of women felt self-collection was easy to operate, 84.61% had no discomfort when using a self-sampling brush, 62. 37% women were more likely to choose self-sampling for cervical cancer screening in the future, 92. 53% were willing to introduce to others around them. Multivariate analysis showed that the reliability of self-sampling and the easy degree of sampling were the independent influencing factors of selecting self-sampling (p<0.05), while no statistical significance was found in different age, education, occupation, gravidity, medical insurance, age of sexual initiation (p>0.05). Conclusions: The Internet-facilitated self-HPV-testing screening and management model for cervical cancer prevention with large sample study is feasible and effective and can be used as a supplement to the traditional screening, especially in marginal areas with few medical resources, finally the coverage of cervical cancer screening will be significantly improved.

Self-Sampling Devices for HPV Testing


 This Horizon Scan summarized the available information regarding the use of self-sampling devices for HPV testing as part of cervical cancer screening programs.
 HPV testing for primary cervical cancer screening is not currently a part of any Canadian screening programs. However, several provinces are in the process of implementation and some pilot testing.
 Self-sampling is generally as accurate as clinician-collected sampling for HPV testing.
 Self-sampling devices for HPV testing could likely be used to increase participation in cervical cancer screening programs.
 Self-sampling for primary HPV screening was highly acceptable to study participants.
 Culturally appropriate care, appropriate educational materials, and providing people with choice in the screening process may contribute to increased uptake of cervical cancer screening.
 Health care providers identified self-sampling as an area where they might benefit from increased knowledge and training.

Abbott Alinity m HR-HPV, a novel human papillomavirus assay for primary cervical cancer screening, is adapted to HPV guidelines

• Abbout Alinity m HR HPV assay is adapted to the new HPV guidelines.

Adherence to follow-up after the exit cervical cancer screening test at age 60-64: A nationwide register-based study.

BackgroundIn Denmark, human papillomavirus (HPV) testing has replaced cytology in primary cervical cancer screening for women aged 60–64; at this age, women are invited for the last (exit) screening test within the national organized program.AimWe investigated the adherence of these women to the recommended follow‐up after a non‐negative (positive or inadequate) HPV test and the overall resource use during that follow‐up.Materials & MethodsWe included all 2926 women aged 60–64 years with nonnegative HPV screening tests between March 2012 and December 2016. All relevant follow‐up tests and procedures were retrieved until the end of 2020 from the highly complete Danish administrative health registers, and the data were linked at the individual level. We determined the extent to which the adherence patterns followed the national recommendations for follow‐up and estimated the total numbers of tests and diagnostic procedures utilized during the entire process.ResultsIn total, only 26% of women had follow‐up in accordance with the recommendations; 4% had no follow‐up, 46% had insufficient follow‐up, and 24% had more follow‐up than recommended. We estimated that 17% of women remained in follow‐up for longer than 4 years. The average numbers of diagnostic tests and procedures used after positive HPV screening were higher than expected, even among women who had insufficient follow‐up, that is, those who received less invasive procedures than recommended, or experienced delays in receiving those procedures.ConclusionTo conclude, we found that the patterns of follow‐up of women with nonnegative primary HPV screening tests at 60–64 often diverged from the recommendations. Addressing these inconsistencies in follow‐up by providing evidence for optimal clinical management should help improve the quality of screening programs and secure an equal and reliable follow‐up care service for all women.

Exploring inclusion of rapid HPV DNA testing in primary cervical cancer screening in Tanzania – role of HIV status

Exploring inclusion of rapid HPV DNA testing in primary cervical cancer screening in Tanzania – role of HIV status

Women’s acceptability of and experience with primary human papillomavirus testing for cervix screening: HPV FOCAL trial cross-sectional online survey results

ObjectiveTo study participant’s acceptability of and attitudes towards human papillomavirus (HPV) testing compared with cytology for cervical cancer screening and what impact having an HPV positive result may have in...

Prevalence of Human Papillomavirus in Women with Abnormal Pap Smears

Background: Human papillomavirus (HPV) is a widely prevalent sexually transmitted virus. Because HPV is the causative agent of cervical cancer, knowledge of the epidemiology of HPV is critical. Objective: To study the prevalence of high-risk human papillomavirus (HR-HPV) in cases of abnormal cervical cytology in Kirkuk city. Methods: In this prospective cross-sectional study, we collected 55 Pap smears samples from women attending Azadi Teaching Hospital and private clinics in Kirkuk over the period from 2012 to 2015. Two specimens were collected from each patient; one for a Pap smear study and the other for PCR assay to detect HPV. Results: HR-HPV was positive in 58.2% of patients. The HR-HPV positivity was highest in the age group 21-30 years (90.9%) and lowest at the age group ≥ 51 years (25%). The highest positive rate was in the group married at age 21-25 years (76.2%) and this rate decreased with progression of the marriage age until reaching (20%) in the age group married at ≥31 years. The largest group was para 3-4 (58.2%), followed by para 1-2 and nulliparous (29.1% and 9.1%, respectively). The highest positive rate was in the group para 3-4 (65.6%). Majority of the patients (67.3%) had ASC-US on cytological diagnosis, while LSIL and HSIL accounting for (18.2%) and (14.5%) respectively. The prevalence of HR-HPV infection rate increases with increasing the grade of abnormality reaching to (80%) and (87.5%) in cases of LSIL and HSIL respectively, while the positivity for ASCUS was ranking (45.9%), which was statistically significant (P-value=0.029), although the positivity in cases of HSIL was more than in the cases of LSIL the difference was statistically not significant (P-value =0.671). Conclusion: It is worthy to add HR-HPV screen by PCR to Pap test to increase the sensitivity of primary screening for cervical cancer. Key words: Abnormal Pap smears, HPV

Clinical Validation of the Onclarity Assay After Assay Migration to the High-Throughput COR Instrument Using SurePath Screening Samples From the Danish Cervical Cancer Screening Program.

ObjectivesThis study presents the clinical assessment of the Onclarity HPV Assay (Becton Dickinson) on the novel COR high-throughput instrument (Becton Dickinson) using the international guidelines in a routine setting.MethodsScreening samples collected in BD SurePath from women aged 30 years and older were used in this validation. Noninferiority of the Onclarity HPV Assay on the COR instrument (Onclarity-COR) was assessed with the comparator assay glycoprotein 5–positive (GP5+)/6+ enzyme immunoassay (GP-EIA) for clinical sensitivity on 122 cervical intraepithelial neoplasia 2 and greater samples. Specificity was assessed using 887 samples with twice-normal cytology. Inter- and intralaboratory reproducibility analysis was assessed using 525 samples. Finally, a time-and-motion study was performed to evaluate COR instrument performance characteristics.ResultsThe Onclarity-COR was noninferior to the GP-EIA for both sensitivity (P = .0016) and specificity (P < .0001). The intralaboratory reproducibility was 98.3% (κ = 0.96), and interlaboratory agreement was 98.5 % (κ = 0.96). The daily hands-on time for the COR instrument was 58 minutes, and walk-away time was 7 hours, 2 minutes per 8-hour day shift.ConclusionsThe Onclarity-COR instrument fulfills international validation criteria on sensitivity, specificity, and laboratory reproducibility. The Onclarity assay’s extended genotyping capability, together with its high-throughput characteristics, makes the COR instrument an excellent candidate for use in human papillomavirus primary cervical cancer screening.

The ASCCP Cervical Cancer Screening Task Force Endorsement and Opinion on the American Cancer Society Updated Cervical Cancer Screening Guidelines

The American Cancer Society (ACS) released updated cervical cancer screening guidelines in 2020 that endorse a shift in practice to primary human papillomavirus (HPV) screening in people with a cervix, beginning at ages of 25-65 years. When access to US Food and Drug Administration-approved primary HPV testing is not available, the ACS offers cotesting or cytology as acceptable alternative strategies but suggests that these testing modalities may be excluded from future iterations of the guidelines. The ASCCP recognizes the benefits and risks of primary HPV cervical cancer screening while acknowledging the barriers to widespread adoption, including implementation issues, the impact of limited HPV vaccination in the United States, and inclusion of populations who may not be well represented on primary HPV screening trials, such as underrepresented minorities. The ASCCP endorses the 2018 US Preventive Services Task Force Recommendation Statement and supports the ACS cervical cancer screening guidelines. Most importantly, the ASCCP endorses any cervical cancer screening for secondary prevention of cervical cancer and recommends interventions that improve screening for those who are underscreened or unscreened.

Long-term cervical precancer outcomes after a negative DNA- or RNA-based human papillomavirus test result

Cervical cancer, a preventable disease associated with the human papillomavirus, is responsible for significant morbidity and mortality globally. Primary human papillomavirus testing is more sensitive in detecting precancerous cervical lesions than cytologic screening and can be conducted using either DNA- or RNA-based assays. Screening programs must select the most appropriate assay from several available assays for their population. It is not yet known whether these assays perform equivalently in the long term, particularly among women with a negative human papillomavirus test result. This study aims to compare long-term safety after a negative human papillomavirus test result across both DNA- and RNA-based testing assays. This study aimed to compare long-term high-grade cervical intraepithelial neoplasia (grade 2 or higher and grade 3 or higher) outcomes of 2 DNA-based assays (Digene Hybrid Capture 2 High-Risk HPV DNA Test and cobas 4800 HPV Test) and 1 messenger RNA-based assay (Aptima HPV Assay) using data from the Human Papillomavirus For Cervical Cancer Trial-DECADEl (FOCAL-DECADE) cohort, by first comparing the positive and negative rates between the assays and then investigating the cumulative incidence of cervical intraepithelial neoplasia grade 2 and higher and grade 3 or higher detection among participants in the FOCAL DECADE cohort over follow-up according to human papillomavirus testing assays. The FOCAL Trial was a randomized controlled trial that evaluated human papillomavirus testing for primary cervical cancer screening. The FOCAL-DECADE cohort subsequently followed FOCAL Trial participants passively through the British Columbia Cervix Screening Program Database for approximately 10 years after the FOCAL Trial study exit to examine the rates of cervical intraepithelial neoplasia grade 2 or higher and grade 3 or higher. For this study, eligible participants had baseline human papillomavirus-negative results from at least 1 assay and had 1 or more cytologic screens after baseline (9509 participants for DNA-based and 3473 participants for DNA- vs RNA-based assay comparisons). We constructed cumulative incidence curves and compared the hazard ratios for cervical intraepithelial neoplasia grade 2 or higher and grade 3 or higher detection according to the assays. Over 10 years of follow-up, the cumulative incidence of cervical intraepithelial neoplasia grade 2 or higher and grade 3 or higher did not significantly differ between the DNA-based assays (hazard ratio, 0.95; 95% confidence interval, 0.84-1.06; P=.35 and hazard ratio, 0.82; 95% confidence interval, 0.66-1.01; P=.06 for cervical intraepithelial neoplasia grade 2 or higher and cervical intraepithelial neoplasia grade 3 or higher, respectively) or between the DNA- and RNA-based assays (hazard ratio, 0.97; 95% confidence interval, 0.87-1.06; P=.48 and hazard ratio, 0.94; 95% confidence interval, 0.79-1.13; P=.52 for cervical intraepithelial neoplasia grade 2 or higher and cervical intraepithelial neoplasia grade 3 or higher, respectively). Among participants who tested negative for human papillomavirus at baseline, the long-term risk of cervical intraepithelial neoplasia grade 2 or higher and grade 3 or higher did not significantly differ regardless of whether DNA- or RNA-based human papillomavirus testing assays were used. Screening program decision makers can be confident that for women who test negative for human papillomavirus, DNA- and RNA-based assays exhibit similar cervical intraepithelial neoplasia grade 2 or higher outcomes over several years.

Assessment of alternative approaches of primary cervical cancer screening among women in low-income environments

Alternative techniques for detecting cancer of the cervix uteri alongside its early precancerous lesions still remain necessary for low income environments since morbidity and mortality due to cervical cancer continues to be on the rise. We recruited one thousand and seventy-seven women aged 15-55 years from selected study hospitals in Eastern Uganda and examined them using Papanicolaou (Pap) smear, direct visual inspection with 5% acetic acid solution (VIA), and human papillomavirus (HPV) DNA testing. Study participants detected with high-grade lesions (HSIL) or cancer cells on Pap smear test, positive VIA test (acetowhite lesions, cervical ulcer or growth), and positive high-risk HPV DNA (relative light units (RLU) were immediately scheduled for colposcopy and cervical biopsy. Of the forty percent of the women confirmed with pap smear positive, 43 of the 63 women had invasive carcinoma (68.3%), while 89 out of 137 women with confirmed biopsy were diagnosed with high grade CIN (CIN2,3) (65%). DVI identified 46 of 63 carcinomas (73%) as well as 47 of 74 high grades CIN (CIN 2, 3) (64%). There was a variation in HPV DNA results due to the cutoff value considered in defining the final result. HPV DNA of high-risk HPV types was detected 39 (61.9%) out the 63 women diagnosed invasive cervical cancer, while 66 (73.3%) or 46 (51%) was detected in the biopsy of women diagnosed with high grade CIN (CIN 2,3). Similarity in identification of high-grade cervical abnormalities was registered by the testing methods. Both VIA and HPV genetic testing methods diagnosed similar numbers of high grade CIN 2,3 and invasive cancer cases as Pap smears. Nevertheless, individual test methods categorized study participants with no cervical disease as being positive. Key words: Visual inspection with acetic acid (VIA), cervical intraepithelial neoplasia (CIN), human papillomavirus (HPV).

Evaluation of p16INK4a immunocytology and human papillomavirus (HPV) genotyping triage after primary HPV cervical cancer screening on self-samples in China

ObjectiveSelf-sampling for human papillomavirus (HPV) testing is an effective option to increase the cervical screening coverage. How to best triage HPV-positive self-samples remains controversial. Here, we evaluated the performance of a novel p16INK4a immunocytology approach (p16) and HPV genotyping in triaging HPV-positive self-samples. MethodsA cohort of 73699 women were screened via SeqHPV assay on self-samples. HPV-positive women who met any sequential positive result of HPV16/18 or VIA or p16 were referred for colposcopy. A triage strategy was considered favorable if the NPV for CIN3+ was ≥98%, combined with an improvement of sensitivity and specificity in comparison to the comparator, being the ‘ASC-US+’ triage and the guideline strategy (HPV16/18+ or ASC-US+). ResultsA total of 3510 HPV-positive women were included, 422 (12.0%) CIN2+ and 247 (7.0%) CIN3+ were identified. The positivity of p16 and ASC-US+ were 36.3% and 22.2%, respectively. p16 was more sensitive and less specific than ASC-US+ (P < 0.0001). However, when combined p16 with cytology or genotypes, two triage strategies were superior to the ‘ASC-US+’ strategy: p16 scored 3+; HPV16/33/58/31+ &p16+. Moreover, four strategies were favorable to the guideline strategy: ASC-US+ or p16+; LSIL+ or p16+; HPV16+ or p16+; HSIL+ or p16+ or HPV16+. These strategies achieved better balance between diseases detection and colposcopy referral. ConclusionsOur findings indicate the promising utility of p16 immunocytology via adjusting the staining score or serving as an ancillary tool to liquid-based cytology or combining with genotyping for the triage of HPV-positive self-samples, which promotes the precise screening of cervical cancer.

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.

DNA methylation marker for the triage of hrHPV positive women in cervical cancer screening: Real-world evidence in Taiwan

ObjectiveHuman papillomavirus (HPV) testing as the primary cervical cancer screening followed by reflex cytology if high-risk HPV is present (hrHPV+) is recently adopted in some countries. However, reflex cytology's sensitivity is variable, and a suitable triage approach for hrHPV+ remains controversial. Here, we compared the performance of three triage tools in hrHPV+ women. MethodsThree triage tools—cytology, HPV16/18 genotyping, and DNA methylation biomarker PAX1m—were analyzed for their clinical performance in hrHPV+ women. In addition, women without cervical cancer at enrollment were followed for histologically confirmed high-grade cervical intraepithelial neoplasia or worse (CIN3+) annually using Papanicolaou smear. ResultsOf 4762 women aged ≥20 years enrolled, 502 (10.5%) were hrHPV+. PAX1m and cytology demonstrated similar accuracy (>90%), sensitivity (>78%), and specificity (>92%) as triage tools in 429 hrHPV+ women aged 30–64 years. PAX1m had better accuracy and specificity (91.6% and 92.5%, respectively) than HPV16/18 (76.9% and 76.8%, respectively). The incidence of CIN3+ among hrHPV+ women was 10.7 cases/1000 person-years. The incidence was significantly greater in PAX1m-positive women than in PAX1m-negative women. ConclusionsPAX1m has comparable clinical performance to cytology and better accuracy and specificity than HPV16/18 as the triage tool for detecting CIN3+ in hrHPV+ women. The PAX1m assay is thus a promising molecular-based triage tool for early detection of CIN and predicting disease progression in hrHPV+ women. It can be especially useful in countries where adequate cytology-based infrastructure is lacking, such as some Southeast Asian countries, for cervical cancer screening and prevention.

Effect of Sequential Rounds of Cervical Cancer Screening on Management of HPV-positive Women: A 15-year Population-based Cohort Study from China.

Women are anticipated to go through more than two rounds of cervical screening in their lifetime. Human papillomavirus (HPV) testing is increasingly used as the primary cervical cancer screening test. However, triage strategies for HPV-positive women were usually evaluated at baseline screening. We assessed the effect of sequential rounds of cervical screening on several algorithms for HPV triage. A total of 1,997 women ages 35-45 years were enrolled in 1999 in Shanxi, P.R. China and followed up three times at approximately 5-year intervals. Cervical intraepithelial neoplasia (CIN) grade 2 or worse (CIN2+) prevalence by prior HPV results and performance of 12 triage algorithms with cytology, genotyping, and prior HPV were examined among 229 HPV-positive women at the fourth round. CIN2+ prevalence varied from 56.5% (95% confidence interval, 36.8%-74.4%) following 15 years HPV persistence to 3.5% (1.2%-9.9%) with an incident HPV within 15 years. Triage with cytology (with threshold of atypical squamous cells of undetermined significance) yielded positive predictive value (PPV) of 21.4% (13.8%-29.0%), entailing immediate colposcopic referral, and negative predictive value (NPV) of 97.4% (94.6%-100%), permitting retesting at short intervals. Triage with genotyping (16/18/31/33/45/52/58) or prior HPV results showed comparable performance with cytology. Among 11 triage algorithms with similar NPV to cytology, triage with prior HPV results and reflex genotyping (16/18) achieved highest PPV of 28.9% (18.8%-39.1%) and lowest colposcopy referral of 33.2% (27.4%-39.5%). HPV persistence across rounds is an effective risk stratifier in HPV-positive women. Mainstream cytology and genotyping, with or without consideration of prior HPV results, remain effective for HPV triage at fourth round. PREVENTION RELEVANCE: The study highlights the sustained effectiveness of mainstream HPV triage methods, such as cytology and genotyping, after sequential rounds of cervical screening. It also suggests that use of HPV persistence across rounds can improve management of HPV-positive women in cervical cancer screening.

Hybrid capture 2 and cobas® 4800: Comparison of performance of two clinically validated tests for human papillomavirus primary screening of cervical cancer.

To compare, in a primary human papillomavirus screening setting, two different validated human papillomavirus tests, considering their analytical and clinical screening performances. In Tuscany, a human papillomavirus screening program was implemented in 2013. Hybrid capture 2 (Qiagen) was used for testing until May 2016, when it was replaced by the cobas® 4800 human papillomavirus test (Cobas; Roche). We evaluated the performance of Hybrid capture 2 and Cobas on: the same screening population in two different periods (before and after changing to Cobas); the same Hybrid capture 2-positive consecutive samples. Discordant samples (Hybrid capture 2-positive/Cobas negative) were typed on the L1 gene (reverse line blot, AB Analitica) and E6/E7 genes (BD Onclarity assay). In the considered time period (n = 37,775), human papillomavirus positivity was 9.8% and 7.4%, respectively, for Hybrid capture 2 and Cobas (p < 0.0001). At immediate colposcopy, the cervical intraepithelial neoplasia, grade 2 positive predictive value was, respectively, 23.8% and 34% (p < 0.001). At one-year recall, human papillomavirus persistence was, respectively, 40.6% and 62.2% (p < 0.0001). Of Hybrid capture 2-positive re-tested samples (n = 620), 32.4% were Cobas negative. Of discordant samples typed on L1, 7% were positive for the 12 high-risk human papillomavirus. Of the samples found to be negative for the 12 high-risk human papillomavirus types on L1, 14.5% were positive on E6/E7 typing. Among the discordant samples, the only two cervical intraepithelial neoplasia (CIN) grade 3 lesions were non-high-risk human papillomavirus positive on both L1 and E6/E7 typing. At baseline, Hybrid capture 2 showed greater human papillomavirus positivity and a lower CIN2+ positive predictive value than Cobas, which was more specific than Hybrid capture 2 in detection of high-risk human papillomavirus: 80% of discordant samples were confirmed as high-risk human papillomavirus negative. This higher analytical specificity determined the non-identification of two CIN3 lesions.

The feasibility of new HPV/DNA test as a primary cervical cancer screening method among 35- years- old ever-married women in Kalutara district; a cross-sectional study

BackgroundCervical cancer is the second commonest female cancer in Sri Lanka. Two major drawbacks of the present cervical cancer screening programme are the suboptimal sensitivity of the pap smear and the low coverage. The objective of the study is to determine the feasibility of a new HPV/DNA test among 35 -years -old ever-married women in a district of Sri Lanka.MethodA community based descriptive cross-sectional study was conducted from 1stof July 2018 to 30th November 2018 in the public health divisions called Medical Officer of Health (MOH) areas of Kalutara district. The study population is comprised of ever-married women 35 years of age. Three women from each cluster (n = 413) were selected by consecutive sampling. A total of 918 women were recruited. HPV/DNA cervical specimen collection (n = 822) was carried out. Cervical specimens were tested by two cytoscreeners with the cobas 4800 PCR based screening machine. Clients’ perceptions and prevalence were assessed. The follow-up of women with positive HPV/DNA screening results was carried out. The operational and technical feasibility of the screening test were assessed. Data entry was done by using the statistical package IBM SPSS version 20.ResultsOverall response rate was 91.1% (n = 836). Clients’ perception was highly positive for HPV/DNA screening test procedure (99.9%, n = 821) and 99.6% (n = 819) of clients had mentioned that the HPV/DNA screening test is worthwhile to be incorporated into the National Cervical Cancer Screening program. The prevalence of HPV was 6.2% (95%CI: 6.18–6.22%). The coverage of the HPV/DNA screening was 89.5%(n = 822). Invalid results reported were 0.12% (n = 1). The percentage of HPV/DNA test positive women who underwent pap test within 3 months of the initial screening was 100% (n = 51), while the percentage of women who attempted to get a colposcopy within the 1 month of referral was 86.7% (n = 13).ConclusionsHPV/DNA test implementation as a primary cervical cancer screening method is feasible among the 35- year age cohort of ever- married women in Kalutara district. It is necessary to further attempt alternative methods of cobas 4800 HPV/DNA test, which would be much suitable for resource-limited settings.