programas cribado cancer


Nota Bibliográfica

Esta Nota es una recopilación de publicaciones (artículos, informes, libros) sobre cribado de cáncer resultado de una revisión no sistemática de la literatura.

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Josep A Espinás. Pla Director d'Oncología de Catalunya.
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Nota bibliográfica cribado c cérvix 2014-10

Burger EA, Kim JJ. The value of improving failures within a cervical cancer screening program: an example from Norway. Int J Cancer. United States; 2014;135(8):1931–9. doi: 10.1002/ijc.28838. PMID: 24615416.

Failures in cervical cancer (CC) screening include nonparticipation, underscreening and loss to follow-up of abnormal results. We estimated the long-term health benefits from and maximum investments in interventions targeted to improving compliance to guidelines while remaining cost-effective. We used a mathematical model empirically calibrated to simulate the natural history of CC in Norway. A baseline scenario reflecting current practice using cytology-based screening was compared to scenarios that target different sources of noncompliance: (i) failure to follow-up women with abnormal results, (ii) screening less frequently than recommended (i.e., underscreening) and (iii) absence of screening. A secondary analysis included human papillomavirus (HPV)-based screening as the primary test. Model outcomes included reductions in lifetime cancer risk and incremental net monetary benefit (INMB) resulting from improvements with compliance. Compared to the status quo, improving all sources of noncompliance leads to important health gains and produced positive INMBs across a range of developed-country willingness-to-pay (WTP) thresholds. For example, a 2% increase in compliance could reduce lifetime cancer risk by 1-3%, depending on the targeted source of noncompliance and primary screening method. Assuming a WTP threshold of $83,000 per year of life saved and cytology-based screening, interventions that increase follow-up of abnormal results yielded the highest INMB per 2% increase in coverage [$19 ($10-21)]. With HPV-based screening, recruiting nonscreeners resulted in the largest INMB [$23 ($18-32)]. Considerable funds could be allocated toward policies that improve compliance with screening under the current cytology-based program or toward adoption of primary HPV-based screening while remaining cost-effective.


Nota bibliográfica cribado c cervix 2014-09

Farnsworth A. Changes to cervical screening in Australia: applying lessons learnt. Med J Aust. 2014;201(5):245–6. Available from: doi: 10.5694/mja14.00935. PMID: 25163361.

Conclusions:Brief written information on overdiagnosis was incompletely understood, but reduced breast screening intentions in a proportion of women, regardless of comprehension. Subjective comprehension was lower among women who had not yet reached screening age but the deterrent effect was higher.British Journal of Cancer advance online publication, 28 August 2014; doi:10.1038/bjc.2014.482

Budd AC, Brotherton JML, Gertig DM, Chau T, Drennan KT, Saville M. Cervical screening rates for women vaccinated against human papillomavirus. Med J Aust. 2014;201(5):279–82. Available from: doi: 10.5694/mja14.00021. PMID: 25163380.

CONCLUSIONS: Despite education messages provided to young women, our results suggest that vaccinated women are being screened at lower rates than unvaccinated women in Australia. While some degree of undermatching of women in the study may have occurred, this cannot wholly explain our findings. Effective implementation of Individual Healthcare Identifiers to health records, including registry records, is needed to prevent potential undermatching of individuals in future linkage studies. In the meantime, efforts to increase participation in cervical screening by vaccinated women are needed


Nota bibliográfica cribado c cérvix 2014-07/08

Hung M-C, Liu M-T, Cheng Y-M, Wang J-D. Estimation of savings of life-years and cost from early detection of cervical cancer: a follow-up study using nationwide databases for the period 2002-2009. BMC Cancer. 2014;14(1):505. Available from:
CONCLUSIONS:Early detection of ICC saves lives and reduces healthcare costs. These health benefits and monetary savings can be used for cost-effectiveness assessments and the promotion of regular proactive screening, especially among older women.
Lazcano-Ponce E, Lőrincz AT, Torres L, Salmerón J, Cruz A, Rojas R, et al. Specimen self-collection and HPV DNA screening in a pilot study of 100,242 women. Int J Cancer. 2014;135(1):109–16. Available from:  doi: 10.1002/ijc.28639. PMID: 24615258.

These findings suggest that large-scale vaginal hrHPV testing in a middle-income country can identify women at greater risk of advanced cervical abnormalities in a programmatically meaningful way but care is warranted to ensure that disease not detectable at colposcopy is kept to a minimum. PASS shows areas that need improvement and sets the stage for wider use of hrHPV screening of self-collected vaginal specimens in Mexico.

Alemany L, de Sanjosé S, Tous S, Quint W, Vallejos C, Shin H-R, et al. Time trends of human papillomavirus types in invasive cervical cancer, from 1940 to 2007. Int J Cancer. 2014;135(1):88–95. Available from: doi: 10.1002/ijc.28636. PMID: 24382655.

Contribution over time of human papillomavirus (HPV) types in human cancers has been poorly documented. Such data is fundamental to measure current HPV vaccines impact in the years to come. We estimated the HPV type-specific distribution in a large international series of invasive cervical cancer (ICC) over 70 years prior to vaccination. Paraffin embedded ICC cases diagnosed between 1940 and 2007 were retrieved from eleven countries in Central-South America, Asia and Europe. Included countries reported to have low-medium cervical cancer screening uptake. Information on age at and year of diagnosis was collected from medical records. After histological confirmation, HPV DNA detection was performed by SPF-10/DEIA/LiPA25 (version1). Logistic regression models were used for estimating the adjusted relative contributions (RC) of HPV16 and of HPV18 over time. Among 4,771 HPV DNA positive ICC cases, HPV16 and HPV18 were the two most common HPVs in all the decades with no statistically significant variations of their adjusted-RC from 1940-59 to 2000-07 (HPV16-from 61.5 to 62.1%, and HPV18-from 6.9 to 7.2%). As well, the RC of other HPV types did not varied over time. In the stratified analysis by histology, HPV16 adjusted-RC significantly increased across decades in adenocarcinomas. Regarding age, cases associated to either HPV16, 18 or 45 were younger than those with other HPV types in all the evaluated decades. The observed stability on the HPV type distribution predicts a high and stable impact of HPV vaccination in reducing the cervical cancer burden in future vaccinated generations.

Wheeler CM, Hunt WC, Cuzick J, Langsfeld E, Robertson M, Castle PE. The influence of type-specific human papillomavirus infections on the detection of cervical precancer and cancer: A population-based study of opportunistic cervical screening in the United States. Int J Cancer. 2014;135(3):624–34. Available from:  doi: 10.1002/ijc.28605. PMID: 24226935.

 There are limited data on the prospective risks of detecting cervical precancer and cancer in United States (US) populations specifically where the delivery of opportunistic cervical screening takes place outside managed care and in the absence of organized national programs. Such data will inform the management of women with positive screening results before and after widespread human papillomavirus (HPV) vaccination and establishes a baseline preceding recent changes in US cervical cancer screening guidelines. Using data reported to the statewide passive surveillance systems of the New Mexico HPV Pap Registry, we measured the 3-year HPV type-specific cumulative incidence of cervical intraepithelial neoplasia grade 2 or more severe (CIN2+) and grade 3 or more severe (CIN3+) detected during real-world health care delivery across a diversity of organizations, payers, clinical settings, providers and patients. A stratified sample of 47,541 cervical cytology specimens from a screening population of 379,000 women underwent HPV genotyping. Three-year risks for different combinations of cytologic interpretation and HPV risk group ranged from CIN2+ and 55% for CIN3+ in women with high-grade (HSIL) cytology and HPV16 infection. A substantial proportion of CIN2+ (35.7%) and CIN3+ (30.9%) were diagnosed following negative cytology, of which 62.3 and 78.2%, respectively, were high-risk HPV positive. HPV16 had the greatest 3-year risks (10.9% for CIN2+,8.0% for CIN3+) followed by HPV33, HPV31, and HPV18. Positive results for high-risk HPV, especially HPV16, the severity of cytologic interpretation, and age contribute independently to the risks of CIN2+ and CIN3+.

Gage JC, Schiffman M, Katki HA, Castle PE, Fetterman B, Wentzensen N, et al. Reassurance Against Future Risk of Precancer and Cancer Conferred by a Negative Human Papillomavirus Test. J Natl Cancer Inst. 2014;106(8). Available from:  doi: 10.1093/jnci/dju153.

Primary human papillomavirus (HPV) testing (without concurrent Pap tests) every 3 years is under consideration in the United States as an alternative to the two recommended cervical cancer screening strategies: primary Pap testing every 3 years, or concurrent Pap and HPV testing (“cotesting”) every 5 years. Using logistic regression and Weibull survival models, we estimated and compared risks of cancer and cervical intraepithelial neoplasia grade 3 or worse (CIN3+) for the three strategies among 1011092 women aged 30 to 64 years testing HPV-negative and/or Pap-negative in routine screening at Kaiser Permanente Northern California since 2003. All statistical tests were two sided. Three-year risks following an HPV-negative result were lower than 3-year risks following a Pap-negative result (CIN3+ = 0.069% vs 0.19%, P < .0001; Cancer = 0.011% vs 0.020%, P < .0001) and 5-year risks following an HPV-negative/Pap-negative cotest (CIN3+ = 0.069% vs 0.11%, P < .0001; Cancer = 0.011% vs 0.014%, P = .21). These findings suggest that primary HPV testing merits consideration as another alternative for cervical screening.

Ibáñez R, Autonell J, Sardà M, Crespo N, Pique P, Pascual A, et al. Protecting the underscreened women in developed countries: the value of HPV test.BMC Cancer. 2014;14:574. Available from:  doi: 10.1186/1471-2407-14-574. PMID: 25102758.

CONCLUSIONS: Underscreened women had high burden of cervical disease. Primary HPV screening followed by cytology triage could be the optimal strategy to identify CIN2+ leading to longer and safe screen intervals.

Kim JJ. Practice-Based Evidence for Primary HPV Testing in the United States. J Natl Cancer Inst. 2014;106(8). Available from:  doi: 10.1093/jnci/dju213.

Morrell S, Qian L. A whole-population profile of HPV testing as a test of cure for high-grade cervical dysplasia in NSW, Australia. J Med Screen. 2014;21(3):151–62. Available from:  doi: 10.1177/0969141314542667. PMID: 24981084.

CONCLUSIONS: Cure rates in women with follow-up testing according to NHMRC guidelines are high. Further studies are needed of the high proportion of women with negative cytology classed as not cured due to HPV positivity, and of the high proportion of women with high grade dysplasia who had one follow-up HPV test only.

Pileggi C, Flotta D, Bianco A, Nobile CGA, Pavia M. Is HPV DNA testing specificity comparable to that of cytological testing in primary cervical cancer screening? Results of a meta-analysis of randomized controlled trials. Int J Cancer. 2014;135(1):166–77. Available from:  doi: 10.1002/ijc.28640. PMID: 24302411.

Therefore, primary screening of cervical cancer by HPV DNA testing appears to offer the right balance between maximum detection of CIN2+ and adequate specificity, if performed in the age group ≥30 years.

Salo H, Nieminen P, Kilpi T, Auranen K, Leino T, Vänskä S, et al. Divergent coverage, frequency and costs of organised and opportunistic Pap testing in Finland.Int J Cancer. 2014;135(1):204–13. Available from:  doi: 10.1002/ijc.28646. PMID: 24347441.

 We evaluated the overall coverage, frequency and costs of Pap testing by screening modality and health care provider in Finland. Information about Pap testing in the Finnish female population of 2.7 million was obtained from nationwide population-based registry data. Among women aged 25-69 years, 87% had had a Pap test taken within or outside the organised programme at least once during the last 5 years and half of those screened in the organised programme had also had at least one Pap test taken outside the programme. Of the annual average of 530,000 Pap tests taken, 84% were taken for screening purposes and 16% as follow-up. Forty percent of the 446,000 annual screening tests were taken in the organised programme, 55% as opportunistic tests in public primary or student health care or by private providers and 5% in public secondary health care. One-fifth of all opportunistic screening Pap tests were taken from women aged organised screening. The total cost of all screening Pap tests was €22.4 million, of which 71% incurred in opportunistic screening. Of the 84,000 annual follow-up Pap tests and their €8.3 million total costs, ∼60% incurred in organised screening or in secondary health care


Nota bibliográfica cribado c cérvix 2014-06

Muwonge R, Wesley RS, Nene BM, Shastri SS, Jayant K, Malvi SG, et al. Evaluation of cytology and visual triage of human papillomavirus-positive women in cervical cancer prevention in India. Int J Cancer. 2014;134(12):2902–9. Available from: doi: 10.1002/ijc.28627. PMID: 24272364.

Cytology triage may be considered in settings where adequate infrastructure exists, whereas VIA triage may be suitable in settings with limited or no cytology infrastructure.

Dugué P-A, Lynge E, Rebolj M. Mortality of non-participants in cervical screening: Register-based cohort study. Int J Cancer. 2014;134(11):2674–82. Available from: doi: 10.1002/ijc.28586. PMID: 24288241.

Non-participants in cervical screening had substantially higher all-cause mortality than participants, and a particularly increased risk of HPV-related causes of death. These results indicate that improper control for the selective uptake of cervical screening may result in overestimating its effectiveness.

Qiao Y-L, Jeronimo J, Zhao F-H, Schweizer J, Chen W, Valdez M, et al. Lower cost strategies for triage of human papillomavirus DNA-positive women. Int J Cancer. 2014;134(12):2891–901. Available from: doi: 10.1002/ijc.28616. PMID: 24248915.

Using human papillomavirus (HPV) testing for cervical cancer screening in lower-resource settings (LRS) will result in a significant number of screen-positive women. This analysis compares different triage strategies for detecting cervical precancer and cancer among HPV-positive women in LRS. This was a population-based study of women aged 25-65 years living in China (n = 7,541). Each woman provided a self-collected and two clinician-collected specimens. The self-collected and one clinician-collected specimen were tested by two HPV DNA tests-careHPVTM and Hybrid Capture 2; the other clinician-collected specimen was tested for HPV16/18/45 E6 protein. CareHPVTM-positive specimens were tested for HPV16/18/45 DNA. HPV DNA-positive women underwent visual inspection with acetic acid (VIA) and then colposcopic evaluation with biopsies. The performance for detection of cervical intraepithelial neoplasia grade 3 or cancer (CIN3+) among HPV DNA-positive women was assessed for different triage strategies: HPV16/18/45 E6 or DNA detection, VIA, colposcopic impression, or higher signal strength (≥10 relative light units/positive control [rlu/pc]). The percent triage positive ranges were 14.8-17.4% for VIA, 17.8-20.9% for an abnormal colposcopic impression; 7.9-10.5% for HPV16/18/45 E6; 23.4-28.4% for HPV16/18/45 DNA; and 48.0-62.6% for higher signal strength (≥10 rlu/pc), depending on the HPV test/specimen combination. The positivity for all triage tests increased with severity of diagnosis. HPV16/18/45 DNA detection was approximately 70% sensitive and had positive predictive values (PPV) of approximately 25% for CIN3+. HPV16/18/45 E6 detection was approximately 50% sensitive with a PPV of nearly 50% for CIN3+. Different triage strategies for HPV DNA-positive women provide important tradeoffs in colposcopy or treatment referral percentages and sensitivity for prevalent CIN3+


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