scholarly journals Is Primary HPV with Secondary p16/Ki67 Dual-Stain an Alternative HSIL-Risk Detection Strategy in Cervical Cancer Screening for Women under 30 Years?

Diagnostics ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 2012
Author(s):  
Martyna Trzeszcz ◽  
Maciej Mazurec ◽  
Robert Jach ◽  
Karolina Mazurec ◽  
Zofia Jach ◽  
...  

Recently, cervical cancer rates elevation has been noted in women aged 20–39 years in regions with a very high human development index (HDI). The onset of cancer elevation rates is observed in the age range of 25–29 years, which should necessitate effective precancer screening in younger age groups, including those <25 years. From 30.066 liquid-based screening tests results (n = 30.066), 3849 liquid-based cytology, 1321 high-risk human papillomavirus (HRHPV) and 316 p16/Ki67 performed in women <30 years were selected. Performance characteristics were calculated for three screening models: primary HRHPV with p16/Ki67 triage, primary cytology with reflex HPV and primary cytology alone. Primary HRHPV with p16/Ki67 triage was significantly more sensitive in high-grade squamous intraepithelial lesion quantified with cervical intraepithelial neoplasia grade 2 or worse [HSIL(CIN2+)] detection than cytology with reflex HRHPV and cytology alone (83.3% vs. 70.8%/45.8%) and had significantly higher diagnostic predictive values (PPV:29.4%/21.3%/22.9%; NPV:91.7%/82.9%/82.2%, respectively at CIN2+ threshold). The number of colposcopies per HSIL(CIN2+) detection indices was 3.4, 4.7 and 4.4, respectively. Primary HPV testing in women <30 years with p16/Ki67 triage of HPV-positive cases might be an effective cervical cancer screening strategy for HSIL(CIN2+) detection with superior diagnostic performance when compared with primary cytology-based models. Women <25 years might also benefit from an introduction to a more sensitive screening approach.

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Pernille Thordal Larsen ◽  
Susanne Fogh Jørgensen ◽  
Mette Tranberg ◽  
Sisse Helle Njor

Abstract Our aim was to investigate whether receiving a false positive (FP) cervical cytology result affected subsequent cervical cancer screening participation. This Danish nationwide register-based cohort study included 502,380 women aged 22.5–45 attending cervical cancer screening in 2012–2014 with a normal (n = 501,003) or FP (n = 1,377) cytology screening result. A FP result was defined as a cervical cytology showing high grade cytological abnormalities followed by a normal or ‘Cervical Intraepithelial Neoplasia grade 1’ biopsy result. Women were categorized as subsequent participants if they had a cervical cytology within 24–42 months after their last screening or surveillance test. We compared subsequent participation among women with a normal versus a FP result, using odds ratios including 95% confidence intervals. Participation was slightly higher among women with FP results than among women with normal results (71.5% vs. 69.2%, p = 0.058). After adjustment for age and screening history, women with FP results participated significantly more than women with normal results (OR: 1.19, 95% CI 1.06–1.35). Women receiving a FP result did not participate less in subsequent cervical cancer screening than women receiving a normal result. In fact, the use of opportunistic screening seemed to be increased among women receiving a FP result.


PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0246902
Author(s):  
Gry St-Martin ◽  
Petra Hall Viborg ◽  
Ane Birgitte Telén Andersen ◽  
Berit Andersen ◽  
Jette Christensen ◽  
...  

Introduction Danish women exit cervical cancer screening at age 65 years, but 23% of cervical cancer cases occur beyond this age. In addition, due to gradual implementation of cervical cancer screening, older women are underscreened by today´s standards. A one-time screening with HPV test was therefore offered to Danish women born before 1948. Methods Register based study reporting histology diagnoses and conizations in women found HPV positive in the one-time screening. Number and proportion of women with severe or non-severe histology results were calculated for screened and HPV-positive women by age group or region of residence. Number of women with biopsy and/or conization per case of cervical intraepithelial neoplasia (CIN) grade 2 or worse (CIN2+) or CIN3+ were also calculated by age groups and region. Results 4,479 (4.1% of screened women) had positive HPV test. 94% of these had one or more additional tests. 2,785 (62%) of HPV-positive women had histology results, and conization was performed in 1,076 (24% of HPV-positive and 1% of all screened women). HPV positivity and CIN3+ detection varied little between regions, but the proportions of HPV positive women undergoing histology varied between regions from 40% to 86% and the proportion with conization from 13% to 36%. Correspondingly, the number of histologies and conizations per CIN3+ detected varied from 5.9 to 11.2 and 1.8 to 4.7, respectively. In total, 514 CIN2+ (0.47% of screened women, 11% of HPV-positive) and 337 CIN3+ (0.31% of screened women, 7.5% of HPV-positive) were diagnosed, including 37 cervical cancer cases. Discussion HPV screening of insufficiently screened birth cohorts can potentially prevent morbidity and mortality from cervical cancer but longer follow-up is needed to see if cancer incidence declines in the screened women in the coming years. Management strategies differed among regions which influenced the proportions undergoing biopsy/conization.


2017 ◽  
Vol 55 (12) ◽  
pp. 3544-3551 ◽  
Author(s):  
N. J. Polman ◽  
A. Oštrbenk ◽  
L. Xu ◽  
P. J. F. Snijders ◽  
C. J. L. M. Meijer ◽  
...  

ABSTRACTHuman papillomavirus (HPV) testing is increasingly being incorporated into cervical cancer screening. The Validation of HPV Genotyping Tests (VALGENT) is a framework designed to evaluate the clinical performance of various HPV tests relative to that of the validated and accepted comparator test in a formalized and uniform manner. The aim of this study was to evaluate the clinical performance of the HPV-Risk assay with samples from the VALGENT-3 panel and to compare its performance to that of the clinically validated Hybrid Capture 2 assay (HC2). The VALGENT-3 panel comprises 1,300 consecutive samples from women participating in routine cervical cancer screening and is enriched with 300 samples from women with abnormal cytology. DNA was extracted from original ThinPrep PreservCyt medium aliquots, and HPV testing was performed using the HPV-Risk assay by investigators blind to the clinical data. HPV prevalence was analyzed, and the clinical performance of the HPV-Risk assay for the detection of cervical intraepithelial neoplasia grade 3 or worse (CIN3+) and CIN2 or worse (CIN2+) relative to the performance of HC2 was assessed. The sensitivity of the HPV-Risk assay for the detection of CIN3+ was similar to that of HC2 (relative sensitivity, 1.00; 95% confidence interval [CI], 0.95 to 1.05;P= 1.000), but the specificity of the HPV-Risk assay was significantly higher than that of HC2 (relative specificity, 1.02; 95% CI, 1.01 to 1.04;P< 0.001). For the detection of CIN2+, similar results were obtained, with the relative sensitivity being 0.98 (95% CI, 0.93 to 1.02;P= 0.257) and the relative specificity being 1.02 (95% CI, 1.01 to 1.03;P< 0.001). The performance of the HPV-Risk assay for the detection of CIN3+ and CIN2+ was noninferior to that of HC2, with allPvalues being ≤0.006. In conclusion, the HPV-Risk assay demonstrated noninferiority to the clinically validated HC2 by the use of samples from the VALGENT-3 panel for test validation and comparison.


2018 ◽  
Vol 34 (3) ◽  
pp. 337-342 ◽  
Author(s):  
Phuong Lien Tran ◽  
Caroline Benski ◽  
Manuela Viviano ◽  
Patrick Petignat ◽  
Christophe Combescure ◽  
...  

Objectives:Colposcopes are expensive, heavy, and need specialized technical service, which may outreach the capacity of low-resource settings. Our aim was to assess the performance of smartphone-based digital images for the detection of cervical intraepithelial neoplasia grade 2 or worse (CIN2+).Methods:Human papillomavirus (HPV)-positive women recruited through a cervical cancer screening campaign had VIA/VILI assessment (visual inspection after application of acetic acid/lugol's iodine). Cervical digital images were captured with a smartphone camera, randomly coded with no prior selection and distributed on an online database (Google Forms) for evaluation. Healthcare providers were invited to evaluate the images and identify CIN2+. The gold standard was the histopathological diagnosis. The sensitivity and specificity for the detection of CIN2+ was assessed for each reader and reported with the 95 percent confidence interval (Clopper-Pearson method).Results:One hundred twenty-five consecutive HPV-positive women were included, with 19 CIN2+ (15.2 percent). Forty-five gynecologists completed the assessment, one-third were considered as experts (>50 colposcopies) and two-thirds as novices (<50 colposcopies). The sensitivity and specificity for CIN 2+ detection was 71.3 percent (67.0–75.7 percent) and 62.4 percent (57.5–67.4 percent), respectively. The performance of novices and experts was similar. The readers assessed 73.1 percent of images as acceptable for diagnostic.Conclusion:Smartphone-based digital images, with its high portability, have a great potential for the diagnosis of CIN2+ in low-resource context.


2021 ◽  
pp. 686-693
Author(s):  
Chemtai Mungo ◽  
Cirilus Ogollah Osongo ◽  
Jeniffer Ambaka ◽  
Magdalene A. Randa ◽  
Benard Samba ◽  
...  

PURPOSE Adjunct cervical cancer screening methods are under evaluation to improve the diagnostic accuracy of human papillomavirus (HPV)-based screening in low- and middle-income countries. We evaluated the feasibility and acceptability of smartphone-based cervicography among HPV-positive women living with HIV (WLWH) in Western Kenya. METHODS HPV-positive WLWH of 25-49 years of age enrolled in a clinical trial (ClinicalTrials.gov identifier: NCT04191967 ) had digital images of the cervix taken using a smartphone by a nonphysician provider following visual inspection with acetic acid. All participants had colposcopy-directed biopsy before treatment. Cervical images were evaluated by three off-site colposcopists for quality, diagnostic utility, and assigned a presumed diagnosis. We determined the proportion of images rates as low, medium, or high quality, interobserver agreement using Cohen’s Kappa statistic, and the off-site colposcopist’s sensitivity and specificity for diagnosis of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) compared with histopathology. Acceptability was evaluated using a questionnaire. RESULTS One hundred sixty-four HPV-positive WLWH underwent cervicography during the study period. Mean age was 37.3 years. Images from the first 94 participants were evaluated by off-site colposcopists, with a majority (70.9%) rated as high quality. Off-site colposcopists had a sensitivity ranging from 21.4% (95% CI, 0.06 to 0.43) to 35.7% (95% CI, 0.26 to 0.46) and a specificity between 85.5% (95% CI, 0.81 to 0.90) to 94.9% (95% CI, 0.92 to 0.98) for diagnosis of CIN2+ based compared with histopathology. The majority of women, 99.4%, were comfortable having an image of their cervix taken as part of screening. CONCLUSION Cervicography by a nonphysician provider as an adjunct to HPV-based screening among WLWH in a low- and middle-income country setting is feasible and acceptable. However, low sensitivity for diagnosis of CIN2+ by off-site expert colposcopists highlights the limitations of cervicography.


2019 ◽  
Vol 31 (7) ◽  
pp. 652-658 ◽  
Author(s):  
Xiaosong Zhang ◽  
Gengli Zhao ◽  
Hui Bi ◽  
Min Zhou ◽  
Xueyin Wang ◽  
...  

Background. To explore the feasibility of careHPV (human papillomavirus) with cytology triage as a cervical cancer screening in rural areas of China. Methods. A total of 7138 women aged 35 to 64 years were divided into 2 groups. Women in careHPV group (n = 3536) underwent careHPV and 288 positive subjects underwent cytology, of which 65 women were ≥ASC-US (atypical squamous cells of undetermined significance). Women in the cytology group (n = 3602) underwent cytology and 111 women were ≥ASC-US. All subjects with ≥ASC-US were referred to colposcopy and biopsy. Results. The average age of subjects was 48.2 ± 7.8 years. In the careHPV group, the HPV-positive rate was 8.1%. The detection rate of ≥ASC-US was 1.8% in the careHPV group and 3.1% in the cytology group ( P = .001). There was no significant difference in detection rate of ≥CINII (cervical intraepithelial neoplasia) in the careHPV group (0.7%) and the cytology group (0.6%; P = .416). In addition, to identify 1 case ≥CINII, an average of 2.6 colposcopies were needed in the careHPV group, and 5.3 colposcopies were performed to diagnose 1 case ≥CINII in the cytology group. Conclusions. careHPV with cytology triage offered similar efficiency in identifying abnormalities of CINII and above compared with cytology screening. With the reduced requirement for cytology testing and colposcopy, careHPV may be a more favorable cervical cancer screening strategy in areas of China where there is a lack of cytology services.


2020 ◽  
Vol 30 (Supplement_5) ◽  
Author(s):  
A Leite ◽  
S Pereira ◽  
D Vaz ◽  
T Smet ◽  
C Portilheiro ◽  
...  

Abstract Background Population-based cervical cancer screening (CCS) are deemed to be more cost-effective than opportunistic screening and to reduce inequalities. Implementation in Portugal has been heterogeneous, at the regional level. In Amadora healthcare cluster (Lisbon area), implementation started in April 2018 in a pilot unit and was scaled-up. We aimed to assess population-based CCS implementation in Amadora. Methods Population-based CCS targets women aged 30-65, and utilises liquid-based cytology with partial HPV genotyping (HPV16/18 and other high-risk HPV - hrHPV). Samples positive for other hrHPV undergo a cytology. HPV16/18+ and other hrHPV+ with ≥ASCUS (atypical squamous cells of undetermined significance) are referred to colposcopy. We assessed implementation according to key indicators extracted from our information system: geographic coverage, number of tests, positive results, positive predictive value of referral (number of cervical intraepithelial neoplasia-CIN/number colposcopies). Results As of 30 August 2019, CCS were in place in 4 of the 9 units, potentially covering 20904 women (48.4% of the target population). 1797 womem performed screening within the programme. Invitation for screening is currently implemented in 1 of the 4 units. Screening results were available for 1702 women, 11,1% were HPV+. From these, 26,5% were HPV 16/18+ and 86.2% positive for other hrHPV. Among the latter, 63.2% were negative for intraepithelial lesion and 36.8% were ≥ASCUS. Overall, of these 189 women, 51.3% (n = 97) were referred for colposcopy. Colposcopy results were available for 37 women, of which 13 had a CIN. PPV of referral was 35.1% (95%confidence interval: 20.7;52.6). Conclusions Despite being a population-based screening most tests are still opportunistic. There is still a limited number of colposcopies results but the current PPV of referral is low and requires further investigation. Implementation towards a full population-based screening in Amadora should continue. Key messages Implementation of a population-based cervical cancer screening in Amadora, Portugal is underway but most screening tests are still applied in an opportunistic manner. A limited number of results is avaliable to estimate positive predictive value of referral to colposcopy. Results available indicate a value of 35.1%, which requires further investigation.


BMJ Open ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. e039636
Author(s):  
Mette Tranberg ◽  
Lone Kjeld Petersen ◽  
Klara Miriam Elfström ◽  
Anne Hammer ◽  
Jan Blaakær ◽  
...  

IntroductionCervical cancer screening ceases between the ages of 60 and 65 in most countries. Yet, a relatively high proportion of cervical cancers are diagnosed in women above the screening age. This study will evaluate if screening of women aged 65–69 years may result in increased detection of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) compared with women not invited to screening. Invited women may choose between general practitioner (GP)-based screening or cervico-vaginal self-sampling. Furthermore, the study will assess if self-sampling is superior to GP-based screening in reaching long-term unscreened women.Methods and analysisThis population-based non-randomised intervention study will include 10 000 women aged 65–69 years, with no record of a cervical cytology sample or screening invitation in the 5 years before inclusion. Women who have opted-out of the screening programme or have a record of hysterectomy or cervical amputation are excluded. Women residing in the Central Denmark Region (CDR) are allocated to the intervention group, while women residing in the remaining four Danish regions are allocated to the reference group. The intervention group is invited for human papillomavirus-based screening by attending routine screening at the GP or by requesting a self-sampling kit. The reference group receives standard care which is the opportunity to have a cervical cytology sample obtained at the GP or by a gynaecologist. The study started in April 2019 and will run over the next 4.5 years. The primary outcome will be the proportion of CIN2+ detected in the intervention and reference groups. In the intervention group, the proportion of long-term unscreened women attending GP-based screening or self-sampling will be compared.Ethics and disseminationThe study has been submitted to the Ethical Committee in the CDR which deemed that the study was not notifiable to the Committee and informed consent is therefore not required. The study is approved by the Danish Data Protection Regulation and the Danish Patient Safety Authority. Results will be disseminated in peer-reviewed journals.Trial registration numberNCT04114968.


2021 ◽  
Vol 13 ◽  
pp. 175883592110109
Author(s):  
Binhua Dong ◽  
Huachun Zou ◽  
Xiaodan Mao ◽  
Yingying Su ◽  
Hangjing Gao ◽  
...  

Background: China’s Fujian Cervical Pilot Project (FCPP) transitioned cervical cancer screening from high-risk human papillomavirus (HR-HPV) nongenotyping to genotyping. We investigated the clinical impact of this introduction, comparing performance indicators between HR-HPV genotyping combined with cytology screening (HR-HPV genotyping period) and the previous HR-HPV nongenotyping combined with cytology screening (HR-HPV nongenotyping period). Methods: A retrospective population-based cohort study was performed using data from the FCPP for China. We obtained data for the HR-HPV nongenotyping period from 1 January 2012 to 31 December 2013, and for the HR-HPV genotyping period from 1 January 2014 to 31 December 2016. Propensity score matching was used to match women from the two periods. Multivariable Cox regression was used to assess factors associated with cervical intraepithelial neoplasia of grade 2 or worse (CIN2+). The primary outcome was the incidence of CIN2+ in women aged ⩾25 years. Performance was assessed and included consistency, reach, effectiveness, adoption, implementation and cost. Results: Compared with HR-HPV nongenotyping period, in the HR-HPV genotyping period, more CIN2+ cases were identified at the initial screening (3.06% versus 2.32%; p < 0.001); the rate of colposcopy referral was higher (10.87% versus 6.64%; p < 0.001); and the hazard ratio of CIN2+ diagnosis was 1.64 (95% confidence interval, 1.43–1.88; p < 0.001) after controlling for health insurance status and age. The total costs of the first round of screening (US$66,609 versus US$65,226; p = 0.293) were similar during the two periods. Higher screening coverage (25.95% versus 25.19%; p = 0.007), higher compliance with age recommendations (92.70% versus 91.69%; p = 0.001), lower over-screening (4.92% versus 10.15%; p < 0.001), and reduced unqualified samples (cytology: 1.48% versus 1.73%, p = 0.099; HR-HPV: 0.57% versus 1.34%, p < 0.001) were observed in the HR-HPV genotyping period. Conclusions: Introduction of an HR-HPV genotyping assay in China could detect more CIN2+ lesions at earlier stages and improve programmatic indicators. Evidence suggests that the introduction of HR-HPV genotyping is likely to accelerate the elimination of cervical cancer in China.


Author(s):  
Alejandra Castanon ◽  
Matejka Rebolj ◽  
Francesca Pesola ◽  
Peter Sasieni

Abstract Background The COVID-19 pandemic has disrupted cervical cancer screening services. Assuming increases to screening capacity are unrealistic, we propose two recovery strategies: one extends the screening interval by 6 months for all and the other extends the interval by 36/60 months, but only for women who have already missed being screened. Methods Using routine statistics from England we estimate the number of women affected by delays to screening. We used published research to estimate the proportion of screening age women with high-grade cervical intraepithelial neoplasia and progression rates to cancer. Under two recovery scenarios, we estimate the impact of COVID-19 on cervical cancer over one screening cycle (3 years at ages 25–49 and 5 years at ages 50–64 years). The duration of disruption in both scenarios is 6 months. In the first scenario, 10.7 million women have their screening interval extended by 6 months. In the second, 1.5 million women (those due to be screened during the disruption) miss one screening cycle, but most women have no delay. Results Both scenarios result in similar numbers of excess cervical cancers: 630 vs. 632 (both 4.3 per 100,000 women in the population). However, the scenario in which some women miss one screening cycle creates inequalities—they would have much higher rates of excess cancer: 41.5 per 100,000 delayed for screened women compared to those with a 6-month delay (5.9 per 100,000). Conclusion To ensure equity for those affected by COVID-19 related screening delays additional screening capacity will need to be paired with prioritising the screening of overdue women.


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