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 2013-09

Crosbie EJ, Einstein MH, Franceschi S, Kitchener HC. Human papillomavirus and cervical cancer. Lancet. 2013;382(9895):889–99.
Available from: doi:
Summary Cervical cancer is caused by human papillomavirus infection. Most human papillomavirus infection is harmless and clears spontaneously but persistent infection with high-risk human papillomavirus (especially type 16) can cause cancer of the cervix, vulva, vagina, anus, penis, and oropharynx. The virus exclusively infects epithelium and produces new viral particles only in fully mature epithelial cells. Human papillomavirus disrupts normal cell-cycle control, promoting uncontrolled cell division and the accumulation of genetic damage. Two effective prophylactic vaccines composed of human papillomavirus type 16 and 18, and human papillomavirus type 16, 18, 6, and 11 virus-like particles have been introduced in many developed countries as a primary prevention strategy. Human papillomavirus testing is clinically valuable for secondary prevention in triaging low-grade cytology and as a test of cure after treatment. More sensitive than cytology, primary screening by human papillomavirus testing could enable screening intervals to be extended. If these prevention strategies can be implemented in developing countries, many thousands of lives could be saved.

Vaccarella S, Lortet-Tieulent J, Plummer M, Franceschi S, Bray F. Worldwide trends in cervical cancer incidence: Impact of screening against changes in disease risk factors. Eur J Cancer. 2013;49(15):3262–73.
 Available from: doi:
Interpretation In countries where effective screening has been in place for a long time the consequences of underlying increases in cohort-specific risk were largely avoided. In the absence of screening, cohort-led increases or, stable, cervical cancer ASRs were observed. Our study underscores the importance of strengthening screening efforts and augmenting existing cancer control efforts with HPV vaccination, notably in those countries where unfavourable cohort effects are continuing or emerging.

Castanon A, Landy R, Sasieni P. How much could primary human papillomavirus testing reduce cervical cancer incidence and morbidity? J Med Screen. 2013;20(2):99–103. Available from: doi: 10.1177/0969141313492313.
 Abstract Human papillomavirus (HPV) testing is being considered as the primary screening test for cervical cancer in England, rather than the currently used cytology test. We aimed to estimate the impact of primary HPV testing on incidence and morbidity of cervical cancer in England by estimating the proportion of cervical cancer diagnosed within 6 years of a negative cytology. We used a population-based case-control study of prospectively recorded data on cervical screening in England between 1988 and 2012, including 8774 women with invasive cervical cancer aged 25 to 64 and 17,341 controls. We used incidence rates in 2010 to estimate absolute risks. We found that 38.8% of all women with cervical cancer had a negative test within 6 years of diagnosis. Assuming HPV testing is 95% sensitive for cancers that would develop over the next 6 years but were missed by cytology, and that 4.3% of those diagnosed by cytology would be missed by HPV testing, we estimate that a maximum of 32.6% of current cases in women invited for screening aged 25 to 64 could be prevented. This translates to a reduction in the rate of cervical cancer in this age group of 4.2 per 100,000 women per year in England, equivalent to 587 cancers.


Nota bibliográfica cribado c cérvix 2013-07/08

Mullins R, Coomber K, Broun K, Wakefield M. Promoting cervical screening after introduction of the human papillomavirus vaccine: the effect of repeated mass media campaigns. Journal of Medical Screening 2013 March 01;20(1):27-32. DOI:10.1177/0969141313478588.

Conclusions A well-researched and carefully pretested television advertising campaign with accurate, actionable messages can elicit appropriate screening behaviour among some of the appropriate groups even in a changed environment of complex, and potentially competing, messages.

Castanon A, Leung VM, Landy R, Lim AW, Sasieni P. Characteristics and screening history of women diagnosed with cervical cancer aged 20-29 years. Br J Cancer 2013 Jul 9;109(1):35-41. DOI:10.1038/bjc.2013.322; PMID:23820257.

Conclusion:Cervical cancer at age 20-24 years is rare. Most cancers in women under age 30 years are screen detected as microinvasive cancer.

Tabuchi T, Hoshino T, Nakayama T, Ito Y, Ioka A, Miyashiro I, et al. Does removal of out-of-pocket costs for cervical and breast cancer screening work? A quasi-experimental study to evaluate the impact on attendance, attendance inequality and average cost per uptake of a Japanese government intervention. Int J Cancer 2013 Aug 15;133(4):972-983. DOI:10.1002/ijc.28095; PMID:23400833.

In conclusion, removing out-of-pocket costs improves female cancer screening uptake in Japan but may not be cost-saving. Although cost removal reduces inequalities in attendance for mammography, it appears to increase inequalities in Pap smear attendance.

Broberg G, Jonasson JM, Ellis J, Gyrd-Hansen D, Anjemark B, Glantz A, et al. Increasing participation in cervical cancer screening: telephone contact with long-term non-attendees in Sweden. Results from RACOMIP, a randomized controlled trial. Int J Cancer 2013 Jul;133(1):164-171. DOI:10.1002/ijc.27985; PMID:23233356.

Telephone contact with women who have abstained from cervical cancer screening for long time increases participation and leads to a significant increase in detection of atypical smears. Cost calculations indicate that this intervention is unlikely to be cost-generating and this strategy is feasible in the context of a screening program.
Barken SS, Lynge E, Andersen ES, Rebolj M. Long-term adherence to follow-up after treatment of cervical intraepithelial neoplasia: nationwide population-based study. Acta Obstet Gynecol Scand 2013 Jul;92(7):852-857. DOI:10.1111/aogs.12116; PMID:23418941.

CONCLUSIONS: Adherence to follow-up after conization was poor in Denmark. Our findings suggest that because of this poor adherence, recommendations for long-term annual follow-up after treatment of cervical intraepithelial neoplasia may not be highly effective. Shorter follow-up schedules using highly sensitive tests appear attractive.

Ostensson E, Hellstrom AC, Hellman K, Gustavsson I, Gyllensten U, Wilander E, et al. Projected cost-effectiveness of repeat high-risk human papillomavirus testing using self-collected vaginal samples in the Swedish cervical cancer screening program. Acta Obstet Gynecol Scand 2013 Jul;92(7):830-840. DOI:10.1111/aogs.12143; PMID:23530870.

BACKGROUND: Human papillomavirus (HPV) testing is not currently used in primary cervical cancer screening in Sweden, and corresponding cost-effectiveness is unclear. OBJECTIVE: From a societal perspective, to evaluate the cost-effectiveness of high-risk (HR)-HPV testing using self-collected vaginal samples. DESIGN: A cost-effectiveness analysis. SETTING: The Swedish organized cervical cancer screening program. METHODS: We constructed a model to simulate the natural history of cervical cancer using Swedish data on cervical cancer risk. For the base-case analysis we evaluated two screening strategies with different screening intervals: (i) cytology screening throughout the woman's lifetime (i.e. "conventional cytology strategy") and (ii) conventional cytology screening until age 35 years, followed by HR-HPV testing using self-collected vaginal samples in women aged >/=35 years (i.e. "combination strategy"). Sensitivity analyses were performed, varying model parameters over a significant range of values to identify cost-effective screening strategies. MAIN OUTCOME MEASURES: Average lifetime cost, discounted and undiscounted life-years gained, reduction in cervical cancer risk, incremental cost-effectiveness ratios with and without the cost of added life-years. RESULTS: Depending on screening interval, the incremental cost-effectiveness ratios for the combination strategy ranged from euro43,000 to euro180,000 per life-years gained without the cost of added life-years, and from euro74,000 to euro206,000 with costs of added life-years included. CONCLUSION: The combination strategy with a 5-year screening interval is potentially cost-effective compared with no screening, and with current screening practice when using a threshold value of euro80,000 per life-years gained.


Nota bibliográfica cribado c cérvix 2013-06

Dijkstra M, van Niekerk D, Rijkaart D, van Kemenade FJ, Heideman DAH, Snijders P, et al. Primary hrHPV DNA testing in Cervical Cancer screening: how to manage screen positive women? A POBASCAM Trial sub study. Cancer Epidemiology Biomarkers & Prevention 2013 June 03 DOI:10.1158/1055-9965.EPI-13-0173.

Conclusions: Triaging hrHPV positive women by cytology at baseline and after 6-12 months, possibly in combination with baseline HPV16/18 genotyping, seems acceptable for cervical cancer screening. Impact: Implementable triage strategies are provided for primary hrHPV screening in an organized setting.

Klug SJ, Neis KJ, Harlfinger W, Malter A, Konig J, Spieth S, et al. A randomized trial comparing conventional cytology to liquid-based cytology and computer assistance. Int J Cancer 2013 Jun 15;132(12):2849-2857. DOI:10.1002/ijc.27955; PMID:23175270.

Liquid-based cytology (LBC) has replaced conventional cytology (CC) for cervical cancer screening in some countries. However, it remains unclear whether LBC is superior to CC. A randomized controlled trial was conducted between August 2007 and March 2009 in Germany to compare LBC, alone and in combination with computer-assisted imaging technology (CAS), to CC in the detection of histologically confirmed cervical intraepithelial neoplasia (CIN). The main outcome measures were detection rates, relative sensitivities, positive predictive values (PPVs) and relative PPVs comparing LBC without and with CAS to CC. Primary histological outcome was CIN2 or higher. Included were 20,627 women participating in opportunistic cervical cancer screening at 20 gynecologic practices. The practices were randomized weekly to use LBC (n = 11,331) or CC (n = 9,296). Patients with positive findings were invited to expert colposcopy. The relative sensitivity of LBC versus CC using the CIN2+ cut-off was 2.74 (95% confidence interval [CI] 1.66-4.53). The relative sensitivity of LBC/CAS versus CC for CIN2+ was 3.17 (95% CI 1.94-5.19). The PPV of LBC and CC for CIN2+ was 48% and 38%, respectively. The PPV ratio did not differ significantly from unity. Differences between LBC and CC were smaller in some sensitivity and subgroup analyses; however, relative sensitivity of LBC remained increased. LBC without and with CAS compared with CC under the field conditions of an opportunistic screening system had a significantly higher sensitivity for the detection of CIN without deterioration of PPVs. Additional use of CAS did not further improve sensitivity of LBC.


Nota bibliográfica cribado c cérvix 2013-05

Patanwala IY, Bauer HM, Miyamoto J, Park IU, Huchko MJ, Smith-McCune KK. A systematic review of randomized trials assessing human papillomavirus testing in cervical cancer screening. Am J Obstet Gynecol 2013 May;208(5):343-353. DOI:10.1016/j.ajog.2012.11.013; PMID:23159693.
Our objective was to assess the sensitivity and specificity of human papillomavirus (HPV) testing for cervical cancer screening in randomized trials. We conducted a systematic literature search of the following databases: MEDLINE, CINAHL, EMBASE, and Cochrane. Eligible studies were randomized trials comparing HPV-based to cytology-based screening strategies, with disease status determined by colposcopy/biopsy for participants with positive results. Disease rates (cervical intraepithelial neoplasia [CIN]2 or greater and CIN3 or greater), sensitivity, and positive predictive value were abstracted or calculated from the articles. Six studies met inclusion criteria. Relative sensitivities for detecting CIN3 or greater of HPV testing-based strategies vs cytology ranged from 0.8 to 2.1. The main limitation of our study was that testing methodologies and screening/management protocols were highly variable across studies. Screening strategies in which a single initial HPV-positive test led to colposcopy were more sensitive than cytology but resulted in higher colposcopy rates. These results have implications for cotesting with HPV and cytology as recommended in the United States.

Malila N, Leinonen M, Kotaniemi-Talonen L, Laurila P, Tarkkanen J, Hakama M. The HPV test has similar sensitivity but more overdiagnosis than the Pap test--a randomised health services study on cervical cancer screening in Finland. Int J Cancer 2013 May 1;132(9):2141-2147. DOI:10.1002/ijc.27850; 10.1002/ijc.27850. PMID:22987601.

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.

Lonnberg S, Nieminen P, Luostarinen T, Anttila A. Mortality audit of the Finnish cervical cancer screening program. Int J Cancer 2013 May 1;132(9):2134-2140. DOI:10.1002/ijc.27844; PMID:22987437.
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.

Snijders PJ, Verhoef VM, Arbyn M, Ogilvie G, Minozzi S, Banzi R, et al. High-risk HPV testing on self-sampled versus clinician-collected specimens: a review on the clinical accuracy and impact on population attendance in cervical cancer screening. Int J Cancer 2013 May 15;132(10):2223-2236. DOI:10.1002/ijc.27790; PMID:22907569.

This review elaborates on the accuracy and feasibility of human papillomavirus (HPV) self-sampling, i.e., offering self-sampling of (cervico-)vaginal cell material by women themselves in nonclinical settings for high-risk HPV (hrHPV) detection in the laboratory, for cervical screening. To that end a bibliographic database search (PubMed) was performed to identify studies (published between January 1992 and January 2012) that compared clinical accuracy of HPV testing on self-sampled material with that of cytology or HPV testing on clinician-taken samples, and studies comparing response to offering HPV self-sampling with a recall invitation. Overall, hrHPV testing on self-samples appeared to be at least as, if not more, sensitive for cervical intraepithelial neoplasia grade 2 or worse (CIN2+) as cytology on clinician-obtained cervical samples, though often less specific. In most studies, hrHPV testing on self- and clinician-sampled specimens is similarly accurate with respect to CIN2+ detection. Variations in clinical performance likely reflect the use of different combinations of collection devices and HPV tests. Because it is known that underscreened women are at increased risk of cervical cancer, targeting non-attendees of the screening program could improve the effectiveness of cervical screening. In developed countries offering self-sampling has shown to be superior to a recall invitation for cytology in re-attracting original non-attendees into the screening program. Additionally, self-testing has shown to facilitate access to cervical screening for women in low resource areas. This updated review of the literature suggests that HPV self-sampling could be an additional strategy that can improve screening performance compared to current cytology-based call-recall programs.


Nota bibliográfica cribado c cervix 2013-03

Cuzick J, Cadman L, Mesher D, Austin J, Ashdown-Barr L, Ho L, et al. Comparing the performance of six human papillomavirus tests in a screening population. Br J Cancer 2013 03/05;108(4):908-913. Enlace:

Conclusion: All HPV tests except NorChip showed high sensitivity for high-grade lesions positive by cytology, suggesting co-testing is unnecessary when using HPV tests. Positivity rates in cytology-negative specimens were similar for the DNA-based tests, but lower for the APTIMA test suggesting this maintains the high sensitivity of DNA tests, but with better specificity.

Casado Buesa MI, García Hernández L, González Enríquez J, Imaz Iglesia I, Rubio González B, Zegarra Salas P. Evaluación económica de la introducción de la vacuna contra el VPH en España para la prevención del cáncer de cuello uterino. IPE 2012/69. 2012;IPE 2012/69.
CONCLUSIONES. La mayor parte de estudios analizados concluyen que la introducción de la
vacunación contra el VPH en niñas adolescentes es una estrategia coste-efectiva, en
comparación con la práctica habitual de cribado desarrollada en cada uno de los
países analizados.
El análisis de los estudios evidencia la existencia de importantes incertidumbres
en la modelización de la historia natural de la enfermedad, tanto de la infección por
VPH como del cáncer de cuello uterino como sobre la eficacia de la vacuna, la
duración de la protección y posterior necesidad de dosis de recuerdo y sobre el
grado de aceptación y coberturas alcanzadas. La efectividad real de las vacunas para
reducir las tasas de incidencia y mortalidad por cáncer de cuello uterino es aún desconocida. Se aprecian asimismo importantes variaciones en los contextos
asistenciales y de cribado de cada uno de los sistemas de salud donde se han realizado
estos estudios.
La estrategia de vacunación más cribado puede ser una opción coste-útil si se
cumplen las asunciones y valores asignados a las variables en el caso base. Pero las
incertidumbres presentes en este tipo de simulaciones y el desconocimiento actual
sobre muchos de los parámetros más relevantes no se pueden obviar: desconocimiento
de la efectividad real de prevención del Cáncer de Cérvix y de la duración de la
protección, de los serotipos circulantes en un futuro próximo, cambios conductuales
frente al riego tras la adquisición de la “falsa seguridad que puede otorgar la vacuna”,
cambios en el cribado de cáncer de cérvix, invariabilidad de los parámetros en el
modelo, evolución de la incidencia del cáncer de cuello uterino y de la eficacia
diagnóstica y terapéutica en las próximas décadas. Junto con los resultados de
estudios similares realizados en distintos contextos, la interpretación de estos
resultados exige máxima prudencia a la hora de su traslado a las recomendaciones
de salud pública.


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