Age-Specific Evaluation of Primary Human Papillomavirus Screening vs Conventional Cytology in a Randomized Setting

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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 ...

Section: Discussionmentioning

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

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“…32 The high CIN2/CIN3 prevalence ratio in our study is due to the high prevalence of CIN2 histology and may be attributed to the following parameters in our study: (i) a high proportion (25%) of women in 20-29 years, an age group that has a higher prevalence of CIN2 36 ; (ii) a higher prevalence of HPV DNA infection (15.7%) compared with other studies (8-10%) 36,37 ; (iii) shorter screening intervals (typically every 1.5-2 years), that may lead to increased detection of transient CIN2 lesions compared with longer screening intervals (every 3-5 years) and (iv) overestimation of CIN2 due to the low reproducibility of CIN2 diagnosis. 7 Both HPV tests were more sensitive than LBC (by >20%Pt), in agreement with earlier studies.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of oncogenic human papillomavirus RNA and DNA tests with liquid‐based cytology in primary cervical cancer screening: The FASE study

Monsonégo

Hudgens

Zerat³

et al. 2010

132

The APTIMA V R HPV Assay (AHPV) allows detection of 14 high-risk human papillomavirus (HPV) RNA types in cervical specimens. Until present, the assay has been compared to HPV DNA tests only in triage settings. Herein, we compare AHPV with a DNA assay (Hybrid Capture V R 2; HC2) and liquid-based cytology (LBC; using PreservCyt V R ThinPrep liquid Pap) in a screening setting (French APTIMA screening evaluation [FASE] study). Women (N 5 5,006) aged 20-65 were screened by gynecologists in 17 private practices in Paris, France. One cervical specimen was collected and tested with LBC, AHPV and HC2 assays. Women were referred to colposcopy if they were ASC-US1 in LBC or HPV positive in either HPV assay. To control for verification bias, a random group (14%) with normal LBC and dually HPV negative tests underwent colposcopy. Data from 4,429 women were analyzed. Sensitivity, specificity and predictive values were calculated for the three tests. AHPV and HC2 were highly sensitive for CIN21 (92.0% and 96.7%) and CIN31 (95.7% and 95.3%) detection and much more sensitive than LBC (69.1% for CIN21 and 73.3% for CIN31). Specificity of AHPV was higher than that of HC2, but similar to that of LBC (p < 0.001). Combining LBC with either HPV test slightly increased sensitivity but compromised specificity. AHPV assay is both specific and sensitive for the detection of high-grade precancerous lesions and may be considered as an option for routine cervical cancer screening for women over 20 years of age.Invasive cervical cancer (ICC) is the second most frequent female cancer worldwide, 1 with an estimation of 493,000 cases annually. ICC incidence and mortality rates have dramatically declined over the past five decades in developed countries, largely due to screening programs based on conventional cervical Papanicolaou (Pap) smears. 2,3 Conventional Pap smear screening, however, has limited sensitivity, positive predictive value (PPV) and reproducibility, which limits its use for primary screening. 3,4-7 Liquid-based cytology (LBC) has been shown to be more sensitive than conventional

“…The screening test has been conventional cytology, with the exception of some municipalities in Southern Finland that participate in a randomized trial with primary HPV DNA testing. 5,6 According to trend and cohort studies, the program has been very effective with decreases in both incidence and mortality of up to 80% by the early 90 s. 7 Since then, some increase in incidence in the younger age groups has been observed. 8 For this audit and impact evaluation study, all 545 deaths attributed to cervical cancer during the period 2000-2009 in Finland were collected from the cancer register and linked to the screening register.…”

Section: Methodsmentioning

confidence: 99%

Mortality audit of the Finnish cervical cancer screening program

Lönnberg

Nieminen

Luostarinen

et al. 2012

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Incidence-based evaluations of cervical cancer screening programs have suggested age-specific impacts and there is uncertainty regarding the effectiveness of screening outside the ages of 30-60 years. We audited the screening histories of cervical cancer deaths and conducted a case-control evaluation of the effectiveness of organized screening in different ages with mortality as outcome. We included all 506 cervical cancer deaths in Finland in 2000-2009 due to cancers diagnosed in 1990 or later, and 3,036 controls matched by age at diagnosis to the cases. Squamous cell carcinoma constituted 59% of the cases, adenocarcinomas 29%, and the remaining 12% were other specified and unspecified cervical malignancies. Most deaths (54%) were due to cancers diagnosed more than 5 years after last screening invitation, 24% were diagnosed among nonattenders and only 14% of deaths occurred among women who had attended invitational screening. The risk reduction associated with attending a single program screen at an age below 40 was nonsignificant (OR 0.70; 95% CI 0.33-1.48), while clear risk reductions were observed after screening at the age of 40-54 (OR 0.33; CI 0.20-0.56) and 55-69 (OR 0.29; CI 0.16-0.54). This study also provides some indication of a long-lasting additional effect of screening at the age of 65. Possible avenues for improving the effectiveness of the Finnish screening program include efforts to increase attendance and an extension of the target ages to include 65-to 69-year-old women. The potential benefit of increasing the sensitivity of the screening test or shortening the screening interval is smaller.The effectiveness of cervical cancer screening by cytology has never been established in a randomized controlled trial, but numerous observational studies have confirmed the considerable potential for prevention of cancer incidence and mortality. 1 However, recent research suggests that screening may not be equally effective in all age-groups currently targeted by screening programmes. 2,3 In a case-control evaluation of the Finnish program, no effect on the risk of cancer in the following 5-year interval was found after participation at the age of 25-29. 2 Risk reductions increased with increasing age up to 40, and remained fairly constant thereafter. Similarly, a case-control study from the UK found screening to be less effective in women aged 20-34 and that the efficacy decreases with decreasing age even within this age range. 3 By contrast, a Swedish audit found screening to be equally effective in preventing cancer diagnosed in the ages 21-29 and 30-65. 4 To our knowledge no mortality based effectiveness studies have yet addressed this issue.The purpose of this study was to audit the screening histories of women who died of cervical cancer and evaluate the impact of participation in organized screening on the mortality from cervical cancer by morphology in different ages. We especially wanted to explore how screening at the age of 65 affects the mortality at advanced ages. Material and MethodsThe cerv...