Routine cervical screening with primary HPV testing and cytology triage protocol in a randomised setting

Kotaniemi-Talonen, Laura; Nieminen, Pekka; Anttila, Ahti; Hakama, Matti

doi:10.1038/sj.bjc.6602799

Cited by 98 publications

(87 citation statements)

References 24 publications

(15 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…4,26 Such an approach does not eliminate the difference between the HPV test and the Pap test, because a positive HPV test was confirmed by the Pap test in the same screening episode in our study. 14 The diagnostic threshold of RLU 1.00 was based on data from clinical materials. For screening purposes, the cut-off level could be increased, as even a level of RLU 10.0 results only in a marginal loss in detection of pre-invasive lesions but improves the specificity of the HPV test substantially.…”

Section: Discussionmentioning

confidence: 99%

“…Screening with the HPV test (Hybrid Capture 2, Digene Corporation, Gaithersburg, MD) was started as a randomised public health policy within the national organised cervical cancer screening programme in 2003. 14 Women of selected municipalities within two screening laboratories were individually randomised in a one-to-one ratio into screening with the HPV test or with the traditional Pap smear (Pap test). By the end of 2007, alltogether 203,788 women were invited in municipalities taking part in the HPV study.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

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

View full text Add to dashboard Cite

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 ...

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

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

View full text Add to dashboard Cite

show abstract

“…This suggests that one could offer HPV as the sole primary test and use cytology only as a triage for women who test HPV positive. 20 Ongoing trials in Finland, 21 the Netherlands, Italy, the United Kingdom and Canada will shed further light on this. Other key issues are the ages at which to start and stop screening and the appropriate interval between screens, which could be age-dependent.…”

Section: Discussionmentioning

confidence: 99%

Overview of the European and North American studies on HPV testing in primary cervical cancer screening

Cuzick¹,

Clavel²,

Petry³

et al. 2006

Intl Journal of Cancer

940

767

View full text Add to dashboard Cite

Several studies suggest that HPV testing is more sensitive than cytology in primary cervical screening. These studies had different designs and were reported in different ways. Individual patient data were collected for all European and North American studies in which cytology was routinely performed and HPV testing was included as an additional parallel test. More than 60,000 women were included. The sensitivity and specificity of HPV testing were compared with routine cytology, both overall and for ages <35, 35-49 and 501. The age-specific prevalence of high risk HPV (hr-HPV) was also analysed. HPV testing was substantially more sensitive in detecting CIN21 than cytology (96.1% vs. 53.0%) but less specific (90.7% vs. 96.3%). The sensitivity of HPV testing was similar in all studies carried out in different areas of Europe and North America, whereas the sensitivity of cytology was highly variable. HPV sensitivity was uniformly high at all ages, whereas the sensitivity of cytology was substantially better in women over the age of 50 than in younger women (79.3% vs. 59.6%). The specificity of both tests increased with age. Positivity rates for HPV testing in women without high-grade CIN were region dependent. These results support the use of HPV testing as the sole primary screening test, with cytology reserved for women who test HPV positive. Large demonstration projects are needed to fully evaluate this strategy. ' 2006 Wiley-Liss, Inc.Key words: HPV testing; cervical screening; sensitivity; specificity; primary screening Currently in Europe and North America, cervical cancer screening is based on exfoliative cytology performed at intervals ranging between 1 and 5 years. Although there has been a marked reduction in incidence and mortality rates of squamous cell carcinoma of the cervix in countries with established cytology screening programmes, 1-3 Sasieni et al. (1996) reported that 47% of women in the UK who developed stage 1B1 or worse invasive cervical cancer before the age of 70 had had an adequate previous screening history. 2 The weaknesses in cytology are 3-fold. First, results are dependent on the high quality sample being collected during examination. Second, the test requires the identification of morphological changes within cells, whose interpretation is highly subjective. Last, this method of screening is particularly repetitive, which can lead to a greater number of interpretive errors. False negative cytology has major medical, economic and legal implications, and this is reflected in high malpractice litigation costs in the US associated with misreading cervical smears.Interest in the use of HPV testing as a screening test is based on the finding that HPV DNA is present in almost all cervical cancers, 4 and the availability of easily performed tests, which have demonstrated higher sensitivity for high grade CIN (CIN21) than that achieved by cytology in several studies. This higher sensitivity offers several potential advantages, including reduced cancer rates and longer screening intervals, ...

show abstract

“…Several studies have shown that hrHPV testing can improve identification of women who have or will develop high-grade cervical intraepithelial neoplasia or cervical cancer (XCIN2) (Clavel et al, 2001;Kulasingam et al, 2002;Cuzick et al, 2003;Peto et al, 2004;Kotaniemi-Talonen et al, 2005;Cuzick et al, 2006).…”

mentioning

confidence: 99%

High-risk HPV type-specific clearance rates in cervical screening

et al. 2007

View full text Add to dashboard Cite

We assessed clearance rates of 14 high-risk human papillomavirus (hrHPV) types in hrHPV-positive women with normal cytology and borderline/mild dyskaryosis (BMD) in a population-based cervical screening cohort of 44 102 women. The 6-month hrHPV type-specific clearance rates, that is, clearance of the same type as detected at baseline, in women with normal and BMD smears were 43% (95% confidence interval (CI) 39 -47) and 29% (95% CI 24 -34), respectively. Corresponding 18-month clearance rates were markedly higher, namely 65% (95% CI 60 -69) and 41% (95% CI 36 -47), respectively. The lowest clearance rates in women with normal cytology were observed for HPV16, HPV18, HPV31, and HPV33. Significantly reduced 18-month clearance rates at a significance level of 1% were observed for HPV16 (49%, 95% CI 41 -59) and HPV31 (50%, 95% CI 39 -63) in women with normal cytology, and for HPV16 (19%, 95% CI 12 -29) in women with BMD. Among women who did not clear hrHPV, women with HPV16 persistence displayed an increased detection rate of XCIN3 (normal Po0.0001; BMD, P ¼ 0.005). The type-specific differences in clearance rates indicate the potential value of hrHPV genotyping in screening programs. Our data support close surveillance (i.e. referral directly, or within 6 months) of women with HPV16 and are inconclusive for surveillance of women with HPV18, HPV31, and HPV33. For the other hrHPV-positive women, it seems advisable to adopt a conservative management with a long waiting period, as hrHPV clearance is markedly higher after 18 months than after 6 months and the risk for XCIN3 is low.

show abstract

Routine cervical screening with primary HPV testing and cytology triage protocol in a randomised setting

Cited by 98 publications

References 24 publications

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

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

Overview of the European and North American studies on HPV testing in primary cervical cancer screening

High-risk HPV type-specific clearance rates in cervical screening

Contact Info

Product

Resources

About