Triaging women with human papillomavirus infection and normal cytology or low‐grade dyskaryosis: evidence from 10‐year follow up of the ARTISTIC trial cohort

Gilham, Clare; Sargent, Alexandra; Peto, Julian

doi:10.1111/1471-0528.15957

Cited by 18 publications

(20 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Translated into clinical practice this would potentially lead to lower colposcopy referrals and less retests elicited by hrHPV positive screening samples. Finally, the retest period could safely be extended to 3 years as was recently proposed for hrHPV positive women with low grade cytology triage outcomes 35 . In perspective, these conclusions support practical pilot implementation of the FAM19A4/miR124‐2 methylation test into cervical screening program's to provide further data and experiences to inform on how a fully molecular cervical screening program can be designed to the benefit of women and health care services both.…”

Section: Resultsmentioning

confidence: 66%

Methylation markers FAM19A4 and miR124‐2 as triage strategy for primary human papillomavirus screen positive women: A large European multicenter study

Bonde

Floore²,

Ejegod

et al. 2020

Intl Journal of Cancer

View full text Add to dashboard Cite

In human papillomavirus (HPV) cervical cancer screening, cytology is used as triage to counter the low specificity of HPV testing. VALID-SCREEN is a EU-multicenter, retrospective study conducted to evaluate the clinical performance of the FAM19A4/ miR124-2 methylation-based molecular triage test as a substitute or addition to cytology as reflex testing of HPV screen positive women. FAM19A4/miR124-2 methylation test (QIAsure Methylation Test) was evaluated in 2384 HPV-positive cervical screening samples, from women 29-76 years of age, derived from four EU countries. Specimens were collected in ThinPrep or SurePath media, HPV-status, concurrent cytology, and histology diagnosis were provided by the parent institutes. The control population consisted of women with no evidence of disease within 2 years of follow-up. A total of 899 histologies were retrieved; 527 showed no disease, 124 CIN2 (5.2%), 228 CIN3 (9.6%) and 20 cervical cancers (0.8%); 19 of 20 screen-detected cervical cancers were found methylation-positive (sensitivity 95%). Overall specificity of FAM19A4/miR124-2 methylation test was 78.3% (n = 2013; 95%CI: 76-80). The negative predictive value of hrHPV positive, methylation-negative outcomes were 99.9% for cervical cancer (N = 1694; 95%CI: 99.6-99.99), 96.9% for ≥CIN3 (95%CI: 96-98), and 93.0% for ≥CIN2 (95%CI: 92-94).

show abstract

Section: Resultsmentioning

confidence: 66%

Methylation markers FAM19A4 and miR124‐2 as triage strategy for primary human papillomavirus screen positive women: A large European multicenter study

Bonde

Floore²,

Ejegod

et al. 2020

Intl Journal of Cancer

View full text Add to dashboard Cite

show abstract

“…The close association between HPV16 infection at baseline and CIN3 + at all three time‐points could be exploited within triage protocols based on partial HPV16 genotyping, to provide a more efficient risk stratification and to reduce the number of colposcopies needed to detect a lesion, as suggested by the recent literature 42 …”

Section: Discussionmentioning

confidence: 99%

Clinical relevance of partial HPV16/18 genotyping in stratifying HPV‐positive women attending routine cervical cancer screening: a population‐based cohort study

Gori

Battagello

Gustinucci³

et al. 2021

BJOG

View full text Add to dashboard Cite

Objective To evaluate partial HPV16/18 genotyping as a possible biomarker to select women attending HPV‐based cervical cancer screening at higher risk to be referred to colposcopy. Design Population‐based cohort study. Setting Organised cervical cancer screening programmes (Italy). Population Women with high‐risk HPV infection (period: 2015–2019). Methods We analysed the association between partial HPV16/18 genotyping, cytology triage and histologically confirmed diagnosis of high‐grade cervical intraepithelial neoplasia (CIN3+) lesions. Main outcome measures Detection rate (DR) and positive predictive value (PPV) for histologically confirmed CIN3+ (any episode in the 2 years after baseline); sensitivity for CIN3+ and number of colposcopies needed for lesion detection. Results The study included 145 437 women screened with HPV testing by the clinically validated COBAS 4800 HPV assay (Roche). Overall, 9601 (6.6%) women were HPV+ at baseline; HPV16 and HPV18 were present in 1865 and 594 samples, respectively. The cumulative (baseline plus 1‐year repeat) cytology positivity was 42.8% and high‐grade cytology was significantly higher (P < 0.0001) among women with HPV16 infection at baseline (15.2%). The cumulative CIN3+ DR for women with HPV16, HPV18 and other HPV‐type infections was 9.8%, 3.4% and 1.8%, respectively. Conclusions Partial HPV16 genotyping may play a role in triage, whereas HPV18 seems to behave much more similarly to the other HPV types and does not provide additional stratification. HPV16 genotyping combined with high‐grade cytology can be envisaged as a triage biomarker in cervical screening to maximise CIN3+ detection while minimising colposcopy at baseline or 1‐year repeat. Tweetable abstract HPV16 genotyping combined with high‐grade cytology can be used as triage biomarker for CIN3+ in HPV‐positive women.

show abstract

“…Another option is an extra triage test for women who are hrHPV positive with ASC-US or another triage method than cytology for all women who are hrHPV positive, such as p16 and Ki-67 dual staining, HPV-16 and HPV-18 genotyping, viral load testing, RNA-based biomarkers, or methylation markers. 28,29 For example, the United States uses HPV-16 and HPV-18 genotyping to differentiate between direct referral to colposcopy or cytology testing as further triage. 30 Many countries, such as England, Finland, the Unites States, and the Netherlands, are using different triage strategies for women who are hrHPV positive.…”

Section: Discussionmentioning

confidence: 99%

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

Loopik

Koenjer

Siebers

et al. 2021

American Journal of Obstetrics and Gynecology

View full text Add to dashboard Cite

BACKGROUND: In 2017, the Dutch cervical cancer screening program had replaced the primary cytology-based screening with primary high-risk human papillomavirus-based screening, including the opportunity to participate through self-sampling. Evaluation and balancing benefit (detection of high-grade cervical intraepithelial neoplasia) and burden of screening (unnecessary referrals, invasive diagnostics, and overtreatment) is needed. OBJECTIVE: This study aimed to compare the referral rates, detection of high-grade cervical intraepithelial neoplasia, overdiagnosis, and overtreatment in the new high-risk human papillomavirus-based screening program, including physician-sampled and self-sampled material, with the previous cytology-based screening program in the Netherlands. STUDY DESIGN: A retrospective cohort study was conducted within the Dutch population-based cervical cancer screening program. Screenees with referrals for colposcopy between 2014 and 2015 (cytology-based screening) and 2017 and 2018 (high-risk human papillomavirus-based screening) were included. Data were retrieved from the Dutch Pathology Registry (PALGA) and compared between the 2 screening programs. The main outcome measures were referral rate, detection of high-grade cervical intraepithelial neoplasia or worse, overdiagnosis (cervical intraepithelial neoplasia grade 1 or less in the histologic specimen), and overtreatment (cervical intraepithelial neoplasia grade 1 or less in the treatment specimen). RESULTS: Of the women included in the study, 19,109 received cytology-based screening, and 26,171 received high-risk human papillomavirus-based screening. Referral rates increased from 2.5% in cytology-based screening to 4.2% in high-risk human papillomavirusbased screening (þ70.2%). Detection rates increased to 46.2% for cervical intraepithelial neoplasia grade 2 or worse, 32.2% for cervical intraepithelial neoplasia grade 3 or worse, and 31.0% for cervical cancer, and overdiagnosis increased to 143.4% with high-risk human papillomavirus-based screening. Overtreatment rates were similar in both screening periods. The positive predictive value of referral for detection of cervical intraepithelial neoplasia grade 2 or worse in high-risk human papillomavirus-based screening was 34.6% compared with 40.2% in cytology-based screening. Women screened through self-sampling were at higher risk of cervical intraepithelial neoplasia grade 2 or worse detection (odds ratio, 1.38; 95% confidence interval, 1.20e1.59) and receiving treatment (odds ratio, 1.31; 95% confidence interval, 1.16e1.48) than those screened through physician-sampling. CONCLUSION: Compared with cytology-based screening, high-risk human papillomavirus-based screening increases detection of highgrade cervical intraepithelial neoplasia, with 462 more cervical intraepithelial neoplasia grade 2 or worse cases per 100,000 women but at the expense of 850 more cases per 100,000 women with invasive diagnostics indicating cervical intraepithelial neoplasia grade 1 or less.

show abstract

Triaging women with human papillomavirus infection and normal cytology or low‐grade dyskaryosis: evidence from 10‐year follow up of the ARTISTIC trial cohort

Cited by 18 publications

References 24 publications

Methylation markers FAM19A4 and miR124‐2 as triage strategy for primary human papillomavirus screen positive women: A large European multicenter study

Methylation markers FAM19A4 and miR124‐2 as triage strategy for primary human papillomavirus screen positive women: A large European multicenter study

Clinical relevance of partial HPV16/18 genotyping in stratifying HPV‐positive women attending routine cervical cancer screening: a population‐based cohort study

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

Contact Info

Product

Resources

About