https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(13)62218-7.pdf

Efficacy of HPV-based screening for prevention of invasive cervical cancer: follow-up of four European randomised controlled trials

Summary Background Human papillomavirus (HPV) testing is known to be more sensitive, but less specific than cytology for detecting cervical intraepithelial neoplasia (CIN). We assessed the efficacy of cervical-cancer screening policies that are based on HPV testing. Methods Between March, 2004, and December, 2004, in two separate recruitment phases, women aged 25–60 years were randomly assigned to conventional cytology or to HPV testing in combination with liquid-based cytology (first phase) or alone (second phase). Randomisation was done by computer in two screening centres and by sequential opening of numbered sealed envelopes in the remaining seven centres. During phase one, women who were HPV-positive and aged 35–60 years were referred to colposcopy, whereas women aged 25–34 years were referred to colposcopy only if cytology was also abnormal or HPV testing was persistently positive. During phase two, women in the HPV group were referred for colposcopy if the HPV test was positive. Two rounds of screening occurred in each phase, and all women had cytology testing only at the second round. The primary endpoint was the detection of grade 2 and 3 CIN, and of invasive cervical cancers during the first and second screening rounds. Analysis was done by intention to screen. This trial is registered, number ISRCTN81678807. Findings In total for both phases, 47 001 women were randomly assigned to the cytology group and 47 369 to HPV testing. 33 851 women from the cytology group and 32 998 from the HPV-testing group had a second round of screening. We also retrieved the histological diagnoses from screening done elsewhere. The detection of invasive cervical cancers was similar for the two groups in the first round of screening (nine in the cytology group vs seven in the HPV group, p=0·62); no cases were detected in the HPV group during round two, compared with nine in the cytology group (p=0·004). Overall, in the two rounds of screening, 18 invasive cancers were detected in the cytology group versus seven in the HPV group (p=0·028). Among women aged 35–60 years, at round one the relative detection (HPV vs cytology) was 2·00 (95% CI 1·44–2·77) for CIN2, 2·08 (1·47–2·95) for CIN3, and 2·03 (1·60–2·57) for CIN2 and 3 together. At round two the relative detection was 0·54 (0·23–1·28) for CIN2, 0·48 (0·21–1·11) for CIN3, and 0·51 (0·28–0·93) for CIN2 and 3 together. Among women aged 25–34 years, there was significant heterogeneity between phases in the relative detection of CIN3. At round one the relative detection was 0·93 (0·52–1·64) in phase one and 3·91 (2·02–7·57) in phase two. At round two the relative detection was 1·34 (0·46–3·84) in phase one and 0·20 (0·04–0·93) in phase two. Pooling both phases, the detection ratio of CIN2 for women aged 25–34 years was 4·09 (2·24–7·48) at round one and 0·64 (0·23–1·27) at round two. Interpretation HPV-based screening is more effective than cytology in preventing invasive cervical cancer, by detecting persistent high-grade lesions earlier and providing a longer low-risk period. However, in younger women, HPV screening leads to over-diagnosis of regressive CIN2. Funding European Union, Italian Ministry of Health, Regional Health Administrations of Piemonte, Tuscany, Veneto and Emilia-Romagna, and Public Health Agency of Lazio.

https://www.thelancet.com/pdfs/journals/lanonc/PIIS1470-2045(09)70360-2.pdf

Efficacy of human papillomavirus testing for the detection of invasive cervical cancers and cervical intraepithelial neoplasia: a randomised controlled trial

Background Neuroblastoma is the second most common type of childhood tumor. It is not known whether screening for neuroblastoma at one year of age reduces the incidence of metastatic disease or mortality due to neuroblastoma. Methods We offered urine screening for neuroblastoma at approximately one year of age to 2,581,188 children in 6 of 16 German states from 1995 to 2000. A total of 2,117,600 eligible children in the remaining states served as controls. We compared the two groups in terms of the incidence of disseminated disease and mortality from neuroblastoma. Results A total of 1,475,773 children (61.2 percent of those who were born between July 1, 1994, and October 31, 1999) underwent screening. In this group, neuroblastoma was detected by screening in 149 children, of whom 3 have died. Fifty-five children who had negative screening tests were subsequently given a diagnosis of neuroblastoma; 14 of these children have died. The screened group and children in the control area had a similar incidence ...

Neuroblastoma screening at one year of age

Rapid increases in cervical adenocarcinoma incidence have been observed in Western countries in recent decades. Postulated explanations include an increasing specificity of subtype-the capability to diagnose the disease, an inability of cytologic screening to reduce adenocarcinoma, and heterogeneity in cofactors related to persistent human papillomavirus infection. This study examines the possible contribution of these factors in relation with trends observed in Europe. Age-period-cohort models were fitted to cervical adenocarcinoma incidence trends in women ages /=3% in Finland, Slovakia, and Slovenia. The increases first affected generations born in the early 1930s through the mid-1940s, with risk invariably higher in women born in the mid-1960s relative to those born 20 years earlier. The magnitude of this risk ratio varied considerably from around 7 in Slovenia to almost unity in France. Declines in period-specific risk were observed in United Kingdom, Denmark, and Sweden, primarily among women ages >30. Whereas increasing specificity of subtype with time may be responsible for some of the increases in several countries, the changing distribution and prevalence of persistent infection with high-risk human papillomavirus types, alongside an inability to detect cervical adenocarcinoma within screening programs, would accord with the temporal profile observed in Europe. The homogeneity of trends in adenocarcinoma and squamous cell carcinoma in birth cohort is consistent with the notion that they share a similar etiology irrespective of the differential capability of screen detection. Screening may have had at least some impact in reducing cervical adenocarcinoma incidence in several countries during the 1990s.

https://cebp.aacrjournals.org/content/cebp/14/9/2191.full.pdf

Incidence Trends of Adenocarcinoma of the Cervix in 13 European Countries

A key determinant of breast cancer outcome in any population is the degree to which cancers are detected at early stages of disease Populations in which cancers are detected at earlier stages have lower breast cancer mortality rates The Breast Health Global Initiative (BHGI) held its third Global Summit in Budapest, Hungary in October 2007, bringing together internationally recognized experts to address the implementation of breast healthcare guidelines for early detection, diagnosis, and treatment in low- and middle-income countries (LMCs) A multidisciplinary panel of experts specifically addressed the implementation of BHGI guidelines for the early detection of disease as they related to resource allocation for public education and awareness, cancer detection methods, and evaluation goals Public education and awareness are the key first steps, because early detection programs cannot be successful if the public is unaware of the value of early detection The effectiveness and efficiency of screening modalities, including screening mammography, clinical breast examination (CBE), and breast self-examination, were reviewed in the context of resource availability and population-based need by the panel Social and cultural barriers should be considered when early detection programs are being established, and the evaluation of early detection programs should include the use of well developed, methodologically sound process metrics to determine the effectiveness of program implementation The approach and scope of any screening program will determine the success of any early detection program as measured by cancer stage at diagnosis and will drive the breadth of resource allocation needed for program implementation

https://onlinelibrary.wiley.com/doi/pdf/10.1002/cncr.23842

M. Hakama

Papers

Evaluation and monitoring of screening programmes