Human papillomavirus DNA testing for the detection of cervical intraepithelial neoplasia grade 3 and cancer: 5-year follow-up of a randomised controlled implementation trial

Bulkmans, Nicole W.J.; Berkhof, Johannes; Rozendaal, Lawrence; Kemenade, Folkert J. van; Boeke, A.J.P.; Bulk, Saskia; Voorhorst, Feja J.; Verheijen, René H.M.; Groningen, K. van; Boon, Mathilde E.; Ruitinga, W.; Ballegooijen, Marjolein van; Snijders, Peter J.F.; Meijer, Chris J.L.M.

doi:10.1016/s0140-6736(07)61450-0

Cited by 573 publications

(554 citation statements)

References 52 publications

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“…The CIN3þ and CIN2þ risks of HPV-positive women with both normal cytology or BMD cytology between younger and older women were comparable. This indicates that HPV screening does not lead to overdiagnosis in younger women, which is supported by results from previous studies (23,24). However, younger HPVnegative women had a significantly higher CIN2þ risk than their older counterparts.…”

Section: Discussionsupporting

confidence: 83%

Five-Year Cervical (Pre)Cancer Risk of Women Screened by HPV and Cytology Testing

Uijterwaal

Polman

Kemenade

et al. 2015

Cancer Prevention Research

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Primary human papillomavirus (HPV)-based cervical screening will be introduced in the Netherlands in 2016. We assessed the 5-year cervical (pre)cancer risk of women with different combinations of HPV and cytology test results. Special attention was paid to risks for cervical intraepithelial neoplasia grade 3 and 2 or more (CIN3þ/2þ) of HPV-positive women with a negative triage test, because this determines the safety of a 5-year screening interval for HPV-positive, triage test-negative women. In addition, agerelated effects were studied. A total of 25,553 women were screened by HPV testing and cytology in a screening setting. Women were managed on the presence of HPV and/or abnormal cytology. Five-year cumulative incidences for CIN3þ/2þ were calculated. Five-year CIN3þ(2þ) risk was 10.0% (17.7%) among HPV-positive women. When stratified by cytology, the CIN3þ (CIN2þ) risk was 7.9% (12.9%) for women with normal cytology and 22.2% (45.3%) for women with equivocal or mildly abnormal (i.e., BMD) cytology. For HPV-negative women, the 5-year CIN3þ(2þ) risk was 0.09% (0.21%). Additional triage of HPVpositive women with normal cytology by repeat cytology at 12 months showed a 5-year CIN3þ(2þ) risk of 4.1% (7.0%). HPVnon 16/18-positive women with normal cytology at baseline had comparable risks of 3.5% (7.9%). HPV-non 16/18-positive women with normal baseline cytology and normal repeat cytology had a 5-year CIN3þ risk of 0.42%. No age-related effects were detected. In conclusion, HPV-positive women with normal cytology and a negative triage test, either repeat cytology after 12 months or baseline HPV 16/18 genotyping, develop a nonnegligible CIN3þ risk over 5 years. Therefore, extension of the screening interval over 5 years only seems possible for HPV screen-negative women. Cancer Prev Res; 8(6); 502-8. Ó2015 AACR.

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Section: Discussionsupporting

confidence: 83%

Five-Year Cervical (Pre)Cancer Risk of Women Screened by HPV and Cytology Testing

Uijterwaal

Polman

Kemenade

et al. 2015

Cancer Prevention Research

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“…Some followup studies have reported preinvasive lesions as benefit of screening. 9,10 Detection rates of any pre-invasive lesion represent a mixture of success in prevention of invasive cancers and harm of overdiagnosis. Therefore, valid observations as to sensitivity are based on interval cancers, i.e., on failure of the screen, and not on lesions identified at screen.…”

Section: Discussionmentioning

confidence: 99%

“…[1][2][3][4][5] The few follow-up studies have focused on pre-invasive lesions and on the length of reassurance that a negative test provides. [6][7][8][9][10] Only few studies have had emphasis on public health aspects. 11,12 The purpose of screening is to prevent invasive cervical cancer and the demonstration of this effect requires follow-up for incident invasive cancers after the screen.…”

mentioning

confidence: 99%

The HPV test has similar sensitivity but more overdiagnosis than the Pap test—A randomised health services study on cervical cancer screening in Finland

Malila

Leinonen

Kotaniemi-Talonen

et al. 2012

Intl Journal of Cancer

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We compared test sensitivity (in terms of prevented cancers) and overdiagnosis (in terms of non-progressive pre-invasive lesions) between the human papillomavirus test (HPV test, Hybrid Capture 2) and the traditional Pap test in routine screening for cervical cancer. The design was a randomised (1:1) health services study in Finland with intake between 2003 and 2007. We estimated sensitivity by the incidence method within one screening round. Overdiagnosis was based on the rate of cervical intraepithelial Grade 3 (CIN3) lesions diagnosed at screen and during the following interval. Out of 203,788 randomised women 132,298 attended (65% in both study arms) and 600,753 person-years accumulated among attenders up to the end of 2010. In all attenders, 34 invasive cervical cancers and 288 CIN3 lesions were diagnosed at screen or during the following interval. The interval cancer incidence was 2.5/10 5 person-years (sensitivity 0.87) and 1.4 (sensitivity 0.93) in the HPV arm and Pap test arm, respectively. The rate of CIN3 lesions was 57.1 and 38.8, respectively. In conclusion, sensitivity of HPV testing was similar to that of Pap testing but caused more overdiagnosis. Therefore, implementation of HPV testing needs to be reconsidered especially in countries with well organised programmes.Recommendations concerning new screening tests for cervical cancer are mostly based on cross-sectional studies and on detection rates of pre-invasive lesions. 1-5 The few follow-up studies have focused on pre-invasive lesions and on the length of reassurance that a negative test provides. 6-10 Only few studies have had emphasis on public health aspects. 11,12 The purpose of screening is to prevent invasive cervical cancer and the demonstration of this effect requires follow-up for incident invasive cancers after the screen. In fact, detection (at screen) of pre-invasive lesions results in both benefit and harm; benefit through preventing some of the lesions from progressing to invasive cancer, and harm by detecting also such pre-invasive lesions that would never have progressed to invasive cancers. These two types of pre-invasive lesions cannot be separated and thus, both types have to be treated if diagnosed.Sensitivity measures a screening test's ability to correctly identify unrecognised disease. It can be estimated in several ways. The most common way is called the detection method 4 which is based on screen detected lesions, both pre-invasive and invasive ones. However, the sensitivity estimate is usually biased and too big (closer to one) due to overdiagnosis of the detection of pre-invasive lesions. Sensitivity can also be estimated by the incidence method 13 that is based on failures of screening.The purpose of the present study was to compare the human papillomavirus (HPV) test to the traditional Pap test in cervical cancer screening in terms of sensitivity (detection of progressive lesions) and overdiagnosis (detection of nonprogressive lesions). Material and methodsIn Finland, women between 30 and 60 years of age (sometimes ...

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“…The study design of the POBASCAM trial (Trial registration ID: NTR218; ISRCTN20781131), a population‐based randomized controlled trial for implementation of high‐risk HPV testing in cervical screening, has been published before 3, 29, 30. In brief, women aged 29–61 were included from January 1999 to September 2002.…”

Section: Methodsmentioning

confidence: 99%

Cervical cancer risk in HPV‐positive women after a negative FAM19A4/mir124‐2 methylation test: A post hoc analysis in the POBASCAM trial with 14 year follow‐up

Strooper

Berkhof

Steenbergen

et al. 2018

Intl Journal of Cancer

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DNA methylation analysis of cervical scrapes using FAM19A4 and mir124‐2 genes has shown a good clinical performance in detecting cervical cancer and advanced CIN lesions in need of treatment in HPV‐positive women. To date, longitudinal data on the cancer risk of methylation test‐negative women are lacking. In our study, we assessed the longitudinal outcome of FAM19A4/mir124‐2 methylation analysis in an HPV‐positive screening cohort with 14 years of follow‐up. Archived HPV‐positive cervical scrapes of 1,040 women (age 29–61 years), who were enrolled in the POBASCAM screening trial (ISRCTN20781131) were tested for FAM19A4/mir124‐2 methylation. By linkage with the nationwide network and registry of histo‐ and cytopathology in the Netherlands (PALGA), 35 cervical cancers were identified during 14 years of follow‐up comprising three screens (baseline, and after 5 and 10 years). The baseline scrape of 36.1% (n = 375) women tested positive for FAM19A4/mir124‐2 methylation, including 24 women with cervical cancer in follow‐up, and 30.6% (n = 318) had abnormal cytology (threshold borderline dyskaryosis or ASCUS), including 14 women with cervical cancer in follow‐up. Within screening round capability of FAM19A4/mir124‐2 methylation to detect cervical cancer was 100% (11/11, 95% CI: 71.5–100). Kaplan–Meier estimate of 14‐year cumulative cervical cancer incidence was 1.7% (95% CI: 0.66–3.0) among baseline methylation‐negative and 2.4% (95% CI: 1.4–3.6) among baseline cytology‐negative women (risk difference: 0.71% [95% CI: 0.16–1.4]). In conclusion, a negative FAM19A4/mir124‐2 methylation test provides a low cervical cancer risk in HPV‐positive women of 30 years and older. FAM19A4/mir124‐2 methylation testing merits consideration as an objective triage test in HPV‐based cervical screening programs.

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Human papillomavirus DNA testing for the detection of cervical intraepithelial neoplasia grade 3 and cancer: 5-year follow-up of a randomised controlled implementation trial

Cited by 573 publications

References 52 publications

Five-Year Cervical (Pre)Cancer Risk of Women Screened by HPV and Cytology Testing

Five-Year Cervical (Pre)Cancer Risk of Women Screened by HPV and Cytology Testing

The HPV test has similar sensitivity but more overdiagnosis than the Pap test—A randomised health services study on cervical cancer screening in Finland

Cervical cancer risk in HPV‐positive women after a negative FAM19A4/mir124‐2 methylation test: A post hoc analysis in the POBASCAM trial with 14 year follow‐up

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