Benefit and burden in the Dutch cytology-based vs high-risk human papillomavirus-based cervical cancer screening program

Loopik, Diede L.; Koenjer, Lisanne M.; Siebers, Albert G.; Melchers, Willem J. G.; Bekkers, Ruud L.M.

doi:10.1016/j.ajog.2020.08.026

Cited by 26 publications

(33 citation statements)

References 27 publications

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“…The finding of increased CIN3+ detection with HPV‐based screening is in line with results of randomized trials 2,3 and other European implementation studies 7,8,23‐27 . The increased CIN detection in our study (≈90% for CIN3+, ≈220% for CIN2+) was higher than in the Dutch HPV‐based program (30% increase in CIN2+) 8,23 and the English pilot (40% increase in CIN2+), 7 but similar to the increase in a Finnish implementation study (250% increase in CIN2+) 24 …”

Section: Discussionsupporting

confidence: 90%

“…In accordance with our results, other implementation studies also found increases in colposcopy referrals when HPV‐based screening was introduced 6‐8,23,25‐27 . The overall colposcopy referral rate in our HPV group (6.6%) was higher than in the Dutch screening program (3.9%‐4.2%), 8,23 although the hrHPV prevalence in the Dutch population (9.2%) was similar to ours (8.9%). Likewise, referral rates in the Australian, Finnish and Italian programs were lower than ours (2.6%‐4.6%) 6,24,28 .…”

Section: Discussionsupporting

confidence: 90%

“…A further finding of our study was that the PPV of colposcopy referral was lower in the HPV group than the cytology group. This is consistent with some 23,25 but not all 7,24,26,27 previous implementations, reflecting that screening algorithms and underlying CIN3+ prevalences differ between countries. In our study, one of five (21.1%) women referred in the HPV group had CIN3+ detected within a year.…”

Section: Discussionsupporting

confidence: 88%

“…Furthermore, we had a very high compliance rate with colposcopy (96%) and repeat screening (92%). Finally, since HPV screening was not yet implemented nationwide in Denmark, we were able to include a contemporary control group screened with cytology, rather than a historical comparison group, as some prior studies 6,8,23,25‐27 …”

Section: Discussionmentioning

confidence: 99%

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Benefits and potential harms of human papillomavirus (HPV)‐based cervical cancer screening: A real‐world comparison of HPV testing versus cytology

Thomsen

Kjær

Munk

et al. 2021

Acta Obstet Gynecol Scand

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Introduction Human papillomavirus (HPV) testing as the primary cervical cancer screening method is implemented in several countries. We report data from the first round of a large Danish pilot implementation of HPV‐based screening. Our aim was to compare colposcopy referrals, detection of high‐grade cervical intraepithelial neoplasia (CIN) and cervical cancer, and positive predictive value (PPV) of colposcopy referral in HPV vs cytology‐based screening. Material and methods From May 2017 to October 2018, women aged 30‐59 years attending cervical cancer screening in the uptake area of the Department of Pathology, Vejle Hospital, Region of Southern Denmark were screened by primary HPV testing (n = 16 067) or primary cytology (n = 23 981) depending on municipality of residence. In the HPV group, women with HPV16/18, or other high‐risk HPV types and abnormal cytology, were referred to immediate colposcopy. Women with other high‐risk HPV types and normal cytology were invited for repeat screening with HPV test and cytology after 12 months. From a nationwide pathology register, we obtained information on screening results and subsequent histological diagnoses during up to 2.9 years after the first screen. PPVs included diagnoses within 1 year after referral. Results In the HPV group, 3.7% were referred to immediate colposcopy and 2.8% were referred at the 12‐month repeat screening. The total referral to colposcopy was higher in the HPV (6.6%) than cytology group (2.1%) (age‐adjusted relative referral = 3.05, 95% confidence interval [CI] 2.75‐3.38). The detection of CIN3+ was higher in the HPV (1.5%) than the cytology group (0.8%) (age‐adjusted relative detection = 1.88, 95% CI 1.56‐2.28). The probability of CIN3+ among women referred to colposcopy (= PPV) was lower in the HPV (21.1%; 95% CI 18.7%‐23.7%) than the cytology group (34.6%; 95% CI 30.7%‐38.9%). In the HPV group, the PPV was lower among women referred at repeat screening (12.1%) than among women referred immediately (27.8%). Conclusions Compared with cytology‐based screening, HPV‐based screening provided a 90% increased CIN3+ detection at the cost of a threefold increase in colposcopy referrals, when considering complete data from the prevalence round. Our findings support implementation of HPV‐based screening in Denmark, but modifications of screening algorithms may be warranted to decrease unnecessary colposcopy referrals.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Benefits and potential harms of human papillomavirus (HPV)‐based cervical cancer screening: A real‐world comparison of HPV testing versus cytology

Thomsen

Kjær

Munk

et al. 2021

Acta Obstet Gynecol Scand

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“…However, many studies found that although co-testing effectively improved the effectiveness of cervical cancer screening, more than 60% of patients who were referred to invasive colposcopy with HSIL are ≤CIN I for pathological results. [6][7][8][9][10][11] Therefore, better triage strategies for colposcopy should be investigated to improve the accuracy of diagnoses and reduce the referral rate of colposcopy.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Cervical High-Grade Squamous Intraepithelial Lesions-Correlated Markers as Triage Strategy for Colposcopy After Co-Testing

Huo¹,

Sun²,

Cao³

et al. 2021

OTT

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Background: Colposcopy was referred in cases with severe abnormalities in co-testing. Although p16/Ki67 dual staining reduced the referral rate, its sensitivity and specificity need to be enhanced. Methods: The expressions of p16, Ki-67, SMAD3, YAP1, RELA were evaluated in the colposcopy referral population. The inclusion criteria included 30-60 years and diagnosed with HPV16/18-positive, other HR-HPV-positive with ASCUS, LSIL, AGC (atypical glandular cell) in co-testing. Colposcopies, endocervical curettages of cervical biopsies were also collected. Cases were excluded if there were no biopsies, if the interval between a cervical screening test and biopsies was more than 6 months, or if insufficient tissue was available as a formalin-fixed paraffin-embedded block. The pathology was independently reviewed by two pathologists. Discrepant interpretations were adjudicated by a third pathologist. Results: In total, 1194 of 1273 cases who were referred to colposcopy were evaluated in the present study. The sensitivity and specificity of p16+ combined with Ki-67+ for predicting CIN2+ were 62.1% and 89.5%, respectively. p16+ combined with YAP1+ and/or RELA+ provided a sensitivity and specificity of 70.9% and 89.5%, respectively, while 72.8% and 86.4% were achieved by p16+ combined with YAP1+ and/or SMAD3+ and/or RELA+. In HPV16/18+ and LSIL subgroups, the sensitivity and specificity of p16+ combined with Ki-67+ for predicting CIN2+ were 67.7% and 87.6%, respectively, for the former group and 58.6%, 88.8%, respectively, for the latter group. p16+, YAP1+/RELA+ showed a better performance for predicting CIN2+ with a better sensitivity and considerable specificity in the other HPV+ combined with ASCUS group than were achieved by p16+ combined with Ki-67+. RELA+ and the combination of p16 and RELA/YAP1 also provided the Max AUC area. Conclusion: Our study shows that RELA and the combination of p16 and RELA/YAP1 achieved better sensitivity and specificity for detecting morphologically CIN2+ lesions.

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Modeling Cervical Cancer Screening Strategies With Varying Levels of Human Papillomavirus Vaccination

et al. 2021

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IMPORTANCE Cervical cancer screening is a lifesaving intervention, with an array of approaches, including liquid-based cytology (LBC), molecular testing for human papillomavirus (HPV) infection, and combinations via parallel cotesting or sequential triage. Maximizing screening efficacy while minimizing overtreatment is vital, especially when considering how the HPV vaccine will affect the interpretation of results. OBJECTIVES To estimate the likely outcomes of different screening modalities and to model how the increasing uptake of the HPV vaccine could affect the interpretation of screening results. DESIGN, SETTING, AND PARTICIPANTS This decision analytic model established a simple Markov model to compare the outcomes of different cervical cancer screening modalities on a simulated population of women (aged Ն25 years), considering different levels of HPV vaccination. MAIN OUTCOMES AND MEASURES The number of cases of cervical intraepithelial neoplasia (CIN) grade 2 and 3 detected and missed, the number of false positives, and the number of tests required to achieve a given level of accuracy. Positive and negative predictive values of different modalities were simulated under varying levels of HPV vaccination and therefore HPV prevalence. RESULTS In a simulated population of 1000 women aged 25 years and older with an HPV prevalence of 2%, HPV-based modalities outperformed LBC-based approaches, detecting 19% more true positives (HPV test sensitivity, 89.9% [95% CI, 88.6%-91.1%]; LBC test sensitivity, 75.5% [95% CI, 66.6%-82.7%]). While cotesting markedly reduced missed cases, detecting 29% more true positives than LBC alone (19.5 [95% CI, 19.3-19.7] per 1000 women screened vs 15.1 [95% CI, 13.3-16.5] per 1000 women screened), it unacceptably increased excess colposcopy referral by 94% (184.4 [95% CI, 181.8-188.0] false positives per 1000 women screened vs 95.1 [95% CI, 93.1-97.0] false positives per 1000 women screened). By contrast, triage testing with reflex screening substantially reduced false positives by a factor of approximately 10 (eg, HPV with LBC triage, 9.6 [95% CI, 9.3-10.0] per 1000 women screened). Over a lifetime of screening, reflex approaches with appropriate test intervals maximized therapeutic efficacy; as HPV vaccination rates increased, HPV-based screening approaches resulted in fewer unnecessary colposcopies than LBC approaches (HPV testing, 80% vaccine coverage: 44.1 [95% CI, 40-45.9] excess colposcopies; LBC testing, 80% vaccine coverage: 96.9 [95% CI, 96.8-97.0] excess colposcopies). CONCLUSIONS AND RELEVANCEIn this decision analytic model, the effectiveness of cervical cancer screening was dependent on the prevalence of cervical dysplasia and/or HPV infection or vaccination in a population as well as the sensitivity and specificity of various modalities. Although screening is lifesaving, overtesting or modalities inappropriate to the target population may cause significant harm, including overtreatment.

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Benefit and burden in the Dutch cytology-based vs high-risk human papillomavirus-based cervical cancer screening program

Cited by 26 publications

References 27 publications

Benefits and potential harms of human papillomavirus (HPV)‐based cervical cancer screening: A real‐world comparison of HPV testing versus cytology

Benefits and potential harms of human papillomavirus (HPV)‐based cervical cancer screening: A real‐world comparison of HPV testing versus cytology

Evaluation of Cervical High-Grade Squamous Intraepithelial Lesions-Correlated Markers as Triage Strategy for Colposcopy After Co-Testing

Modeling Cervical Cancer Screening Strategies With Varying Levels of Human Papillomavirus Vaccination

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