Sant'Ambrogio di Torino, Italy
Sant'Ambrogio di Torino, Italy

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Giorgi Rossi P.,Epidemiology Unit | Giorgi Rossi P.,Instituto Of Ricovero E Cura A Carattere Scientifico Irccs | Carozzi F.,Cancer Prevention and Research Institute | Federici A.,Italian Ministry of Health | And 3 more authors.
Preventive Medicine | Year: 2016

In Italy, the cohorts of women who were offered Human papillomavirus (HPV) vaccination in 2007/08 will reach the age (25. years) for cervical cancer (CC) screening from 2017. The simultaneous shift from cytology-based screening to HPV test-based screening gives the opportunity for unprecedented reorganisation of CC prevention. The ONS (National Screening Monitoring Centre) Directive and the GISCi (Italian Group for Cervical Screening) identified the consensus conference as the most suitable method for addressing this topic. A summary of consensus recommendations is reported here. The main objective was to define the best screening methods in girls vaccinated against HPV and the knowledge required for defining evidence-based screening strategies. A Jury made recommendations about questions and proposals formulated by a panel of experts representative of Italian scientific societies involved in CC prevention and based on systematic reviews of literature and evidence. The Jury considered changing the screening protocols for girls vaccinated in their twelfth year as appropriate. Tailored screening protocols based on vaccination status could be replaced by "one size fits all" protocols only when a herd immunity effect has been reached. Vaccinated women should start screening at age 30, instead of 25, with HPV test. Furthermore, there is a strong rationale for applying longer intervals for re-screening HPV negative women than the currently recommended 5. years, but research is needed to determine the optimal screening time points. For non-vaccinated women and for women vaccinated in their fifteenth year or later, the current protocol should be kept. © 2016.


Costantini A.S.,Cancer Prevention and Research Institute ISPO | Gallo F.,Center for Cancer Epidemiology and Prevention | Pega F.,University of Otago | Pega F.,Harvard University | And 3 more authors.
International Journal of Epidemiology | Year: 2015

Background: This article is part of a series commissioned by the International Epidemiological Association, aimed at describing population health and epidemiological resources in the six World Health Organization (WHO) regions. It covers 32 of the 53 WHO European countries, namely the Western European countries, the Balkan countries and the Baltic countries. Methods: The burdens of mortality and morbidity and the patterns of risk factors and inequalities have been reviewed in order to identify health priorities and challenges. Literature and internet searches were conducted to stock-take epidemiological teaching, research activities, funding and scientific productivity. Findings: These countries have among the highest life expectancies worldwide. However, within-and between-country inequalities persist, which are largely due to inequalities in distribution of main health determinants. There is a long tradition of epidemiological research and teaching in most countries, in particular in the Western European countries. Cross-national networks and collaborations are increasing through the support of the European Union which fosters procedures to standardize educational systems across Europe and provides funding for epidemiological research through framework programmes. The number of Medline-indexed epidemiological research publications per year led by Western European countries has been increasing. The countries accounts for nearly a third of the global epidemiological publication. Conclusions: Although population health has improved considerably overall, persistent withinand between-country inequalities continue to challenge national and European health institutions. More research, policy and action on the social determinants of health are required in the region. Epidemiological training, research and workforce in the Baltic and Balkan countries should be strengthened. European epidemiologists can play pivotal roles andmust influence legislation concerning production and access to high-quality data. © The Author 2015.


Bergeron C.,Laboratoire Cerba | Ronco G.,Center for Cancer Epidemiology and Prevention | Reuschenbach M.,German Cancer Research Center | Wentzensen N.,U.S. National Cancer Institute | And 3 more authors.
International Journal of Cancer | Year: 2015

Cervical cancer screening test performance has been hampered by either lack of sensitivity of Pap cytology or lack of specificity of Human Papillomavirus (HPV) testing. This uncertainty can lead to unnecessary referral and treatment, which is disturbing for patients and increases costs for health care providers. The identification of p16INK4a as a marker for neoplastic transformation of cervical squamous epithelial cells by HPVs allows the identification of HPV-transformed cells in histopathology or cytopathology specimens. Diagnostic studies have demonstrated that the use of p16INK4a immunohistochemistry substantially improves the reproducibility and diagnostic accuracy of histopathologic diagnoses. p16INK4a cytology has substantially higher sensitivity for detection of cervical precancer in comparison to conventional Pap tests. Compared to HPV DNA tests, immunochemical detection of p16INK4a-stained cells demonstrates a significantly improved specificity with remarkably good sensitivity. About 15 years after the initial observation that p16INK4a is overexpressed in HPV-transformed cells we review the accumulated clinical evidence suggesting that p16INK4a can serve as a useful biomarker in the routine diagnostic work up of patients with HPV infections and associated lesions of the female anogenital tract. © 2014 The Authors. Published by Wiley Periodicals, Inc. on behalf of UICC.


Ronco G.,Center for Cancer Epidemiology and Prevention | Dillner J.,Karolinska Institutet | Elfstrom K.M.,Karolinska Institutet | Tunesi S.,Center for Cancer Epidemiology and Prevention | And 31 more authors.
The Lancet | Year: 2014

Background: In four randomised trials, human papillomavirus (HPV)-based screening for cervical cancer was compared with cytology-based cervical screening, and precursors of cancer were the endpoint in every trial. However, direct estimates are missing of the relative efficacy of HPV-based versus cytology-based screening for prevention of invasive cancer in women who undergo regular screening, of modifiers (eg, age) of this relative efficacy, and of the duration of protection. We did a follow-up study of the four randomised trials to investigate these outcomes. Methods: 176 464 women aged 20-64 years were randomly assigned to HPV-based (experimental arm) or cytology-based (control arm) screening in Sweden (Swedescreen), the Netherlands (POBASCAM), England (ARTISTIC), and Italy (NTCC). We followed up these women for a median of 6·5 years (1 214 415 person-years) and identified 107 invasive cervical carcinomas by linkage with screening, pathology, and cancer registries, by masked review of histological specimens, or from reports. Cumulative and study-adjusted rate ratios (experimental vs control) were calculated for incidence of invasive cervical carcinoma. Findings: The rate ratio for invasive cervical carcinoma among all women from recruitment to end of follow-up was 0·60 (95% CI 0·40-0·89), with no heterogeneity between studies (p=0·52). Detection of invasive cervical carcinoma was similar between screening methods during the first 2·5 years of follow-up (0·79, 0·46-1·36) but was significantly lower in the experimental arm thereafter (0·45, 0·25-0·81). In women with a negative screening test at entry, the rate ratio was 0·30 (0·15-0·60). The cumulative incidence of invasive cervical carcinoma in women with negative entry tests was 4·6 per 105 (1·1-12·1) and 8·7 per 105 (3·3- 18·6) at 3·5 and 5·5 years, respectively, in the experimental arm, and 15·4 per 105 (7·9-27·0) and 36·0 per 105 (23·2-53·5), respectively, in the control arm. Rate ratios did not differ by cancer stage, but were lower for adenocarcinoma (0·31, 0·14-0·69) than for squamous-cell carcinoma (0·78, 0·49-1·25). The rate ratio was lowest in women aged 30-34 years (0·36, 0·14-0·94). Interpretation: HPV-based screening provides 60-70% greater protection against invasive cervical carcinomas compared with cytology. Data of large-scale randomised trials support initiation of HPV-based screening from age 30 years and extension of screening intervals to at least 5 years. Funding: European Union, Belgian Foundation Against Cancer, KCE-Centre d'Expertise, IARC, The Netherlands Organisation for Health Research and Development, the Italian Ministry of Health.


Rossi P.G.,Azienda Unita Sanitaria Locale Of Reggio Emilia | Baldacchini F.,Azienda Unita Sanitaria Locale Of Reggio Emilia | Ronco G.,Center for Cancer Epidemiology and Prevention
Frontiers in Oncology | Year: 2014

Background: Screening with HPV is more effective than Pap test in preventing cervical cancer. HPV as primary test will imply longer intervals and a triage test for HPV positive women. It will also permit the development of self-sampling devices. These innovations may affect population coverage, participation, and compliance to protocols, and likely in a different way for less educated, poorer, and disadvantaged women.Aim: To describe the impact on inequalities, actual or presumed, of the introduction of HPV-based screening. Methods: The putative HPV-based screening algorithm has been analyzed to identify critical points for inequalities. A systematic review of the literature has been conducted searching PubMed on HPV screening coverage, participation, and compliance. Results were summarized in a narrative synthesis. Results: Knowledge about HPV and cervical cancer was lower in women with low socio-economic status and in disadvantaged groups. A correct communication can reduce differences. Longer intervals will make it easier to achieve high-population coverage, but higher cost of the test in private providers could reduce the use of opportunistic screening by disadvantaged women. There are some evidences that inviting for HPV test instead of Pap increases participation, but there are no data on social differences. Self-sampling devices are effective in increasing participation and coverage. Some studies showed that the acceptability of self-sampling is higher in more educated women, but there is also an effect on hard-to-reach women. Communication of HPV positivity may increase anxiety and impact on sexual behaviors, the effect is stronger in low educated and disadvantaged women. Finally, many studies found indirect evidence that unvaccinated women are or will be more probably under-screened. Conclusion: The introduction of HPV test may increase population coverage, but non-compliance to protocols and interaction with opportunistic screening can increase the existing inequalities.


Veldhuijzen N.J.,VU University Amsterdam | Berkhof J.,VU University Amsterdam | Gillio-Tos A.,University of Turin | De Marco L.,University of Turin | And 5 more authors.
Cancer Epidemiology Biomarkers and Prevention | Year: 2015

Background: Age-and type-specific high-risk human papillomavirus (hrHPV) incidence estimates in screen-eligible women are relevant from a public health perspective because they provide an indication of the effect of vaccination on the occurrence of screen-positives in HPV-based screening. However, limited data from women over 25 years of age are available. Methods: In 24,105 hrHPV-negative women participating in Dutch (Population-Based Screening Study Amsterdam: POBASCAM) and Italian (New Technologies for Cervical Cancer: NTCC) population-based randomized controlled screening trials the ageand type-specific distribution of incident hrHPV infections detected at the next screening round was assessed. HPV types were grouped into vaccine (bivalent: HPV16/18; polyvalent HPV16/18/31/33/45/52/58) and nonvaccine types. Results: The incidence of screen-detected hrHPV among women ages 29 to 56 years was 2.54% (95% confidence interval, 2.30-2.78) in POBASCAM and 2.77% (2.36-3.19) in NTCC. In both studies, the incidence of bivalent, polyvalent, and nonpolyvalent infections decreased with age (P < 0.0001). Among women with incident infection(s), vaccine-type positivity changed quadratically with age, in particular for the polyvalent vaccine (P values: POBASCAM: bivalent 0.264, polyvalent 0.038; NTCC bivalent 0.039, polyvalent 0.005). However, more than 20% and 50% of women with incident hrHPV were positive for bivalent and polyvalent vaccine types, respectively, in all ages in both studies. Conclusions: We observed decreasing age trends of hrHPV vaccine and nonvaccine type incidences and age-related differences in the vaccine-type positivity among women with incident infections. Most importantly, hrHPV infections continued to be detected in all ages and the contribution of vaccine types remained substantial. Impact: Our results indicate a considerable reduction of new hrHPV infections in vaccinated cohorts, ensuing revision of screening guidelines. © 2014 American Association for Cancer Research.


PubMed | Karolinska Institutet, University of Manchester, International Agency for Research on Cancer IARC, Scientific Institute of Public Health and 4 more.
Type: Comparative Study | Journal: Lancet (London, England) | Year: 2014

In four randomised trials, human papillomavirus (HPV)-based screening for cervical cancer was compared with cytology-based cervical screening, and precursors of cancer were the endpoint in every trial. However, direct estimates are missing of the relative efficacy of HPV-based versus cytology-based screening for prevention of invasive cancer in women who undergo regular screening, of modifiers (eg, age) of this relative efficacy, and of the duration of protection. We did a follow-up study of the four randomised trials to investigate these outcomes.176,464 women aged 20-64 years were randomly assigned to HPV-based (experimental arm) or cytology-based (control arm) screening in Sweden (Swedescreen), the Netherlands (POBASCAM), England (ARTISTIC), and Italy (NTCC). We followed up these women for a median of 65 years (1,214,415 person-years) and identified 107 invasive cervical carcinomas by linkage with screening, pathology, and cancer registries, by masked review of histological specimens, or from reports. Cumulative and study-adjusted rate ratios (experimental vs control) were calculated for incidence of invasive cervical carcinoma.The rate ratio for invasive cervical carcinoma among all women from recruitment to end of follow-up was 060 (95% CI 040-089), with no heterogeneity between studies (p=052). Detection of invasive cervical carcinoma was similar between screening methods during the first 25 years of follow-up (079, 046-136) but was significantly lower in the experimental arm thereafter (045, 025-081). In women with a negative screening test at entry, the rate ratio was 030 (015-060). The cumulative incidence of invasive cervical carcinoma in women with negative entry tests was 46 per 10(5) (11-121) and 87 per 10(5) (33-186) at 35 and 55 years, respectively, in the experimental arm, and 154 per 10(5) (79-270) and 360 per 10(5) (232-535), respectively, in the control arm. Rate ratios did not differ by cancer stage, but were lower for adenocarcinoma (031, 014-069) than for squamous-cell carcinoma (078, 049-125). The rate ratio was lowest in women aged 30-34 years (036, 014-094).HPV-based screening provides 60-70% greater protection against invasive cervical carcinomas compared with cytology. Data of large-scale randomised trials support initiation of HPV-based screening from age 30 years and extension of screening intervals to at least 5 years.European Union, Belgian Foundation Against Cancer, KCE-Centre dExpertise, IARC, The Netherlands Organisation for Health Research and Development, the Italian Ministry of Health.


PubMed | Azienda Unita Sanitaria Locale Of Reggio Emilia and Center for Cancer Epidemiology and Prevention
Type: | Journal: Frontiers in oncology | Year: 2014

Screening with HPV is more effective than Pap test in preventing cervical cancer. HPV as primary test will imply longer intervals and a triage test for HPV positive women. It will also permit the development of self-sampling devices. These innovations may affect population coverage, participation, and compliance to protocols, and likely in a different way for less educated, poorer, and disadvantaged women.To describe the impact on inequalities, actual or presumed, of the introduction of HPV-based screening.The putative HPV-based screening algorithm has been analyzed to identify critical points for inequalities. A systematic review of the literature has been conducted searching PubMed on HPV screening coverage, participation, and compliance. RESULTS were summarized in a narrative synthesis.Knowledge about HPV and cervical cancer was lower in women with low socio-economic status and in disadvantaged groups. A correct communication can reduce differences. Longer intervals will make it easier to achieve high-population coverage, but higher cost of the test in private providers could reduce the use of opportunistic screening by disadvantaged women. There are some evidences that inviting for HPV test instead of Pap increases participation, but there are no data on social differences. Self-sampling devices are effective in increasing participation and coverage. Some studies showed that the acceptability of self-sampling is higher in more educated women, but there is also an effect on hard-to-reach women. Communication of HPV positivity may increase anxiety and impact on sexual behaviors, the effect is stronger in low educated and disadvantaged women. Finally, many studies found indirect evidence that unvaccinated women are or will be more probably under-screened.The introduction of HPV test may increase population coverage, but non-compliance to protocols and interaction with opportunistic screening can increase the existing inequalities.


PubMed | Instituto Of Ricovero E Cura A Carattere Scientifico Irccs, International Agency for Research on Cancer, Cancer Prevention and Research Institute, Unit of Clinical and Descriptive Epidemiology and 2 more.
Type: | Journal: Preventive medicine | Year: 2016

In Italy, the cohorts of women who were offered Human papillomavirus (HPV) vaccination in 2007/08 will reach the age for cervical cancer (CC) screening from 2017. The simultaneous shift from cytology-based screening to HPV test-based screening gives the opportunity for unprecedented reorganisation of CC prevention. The ONS (National Screening Monitoring Centre) Directive and the GISCi (Italian Group for Cervical Screening) identified the consensus conference as the most suitable method for addressing this topic. A summary of consensus recommendations is reported here. The main objective was to define the best screening methods in girls vaccinated against HPV and the knowledge required for defining evidence-based screening strategies. A Jury made recommendations about questions and proposals formulated by a panel of experts representative of Italian scientific societies involved in CC prevention and based on systematic reviews of literature and evidence. The Jury considered changing the screening protocols for girls vaccinated in their twelfth year as appropriate. Tailored screening protocols based on vaccination status could be replaced by one size fits all protocols only when a herd immunity effect has been reached. Vaccinated women should start screening at age 30, instead of 25, with HPV test. Furthermore, there is a strong rationale for applying longer intervals for re-screening HPV negative women than the currently recommended 5years, but research is needed to determine the optimal screening time points. For non-vaccinated women and for women vaccinated in their fifteenth year or later, the current protocol should be kept.


PubMed | University of Turin, VU University Amsterdam, Veneto Institute of Oncology IOV IRCCS, Center for Cancer Epidemiology and Prevention and Cancer Prevention and Research Institute ISPO
Type: Journal Article | Journal: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology | Year: 2015

Age- and type-specific high-risk human papillomavirus (hrHPV) incidence estimates in screen-eligible women are relevant from a public health perspective because they provide an indication of the effect of vaccination on the occurrence of screen-positives in HPV-based screening. However, limited data from women over 25 years of age are available.In 24,105 hrHPV-negative women participating in Dutch (Population-Based Screening Study Amsterdam: POBASCAM) and Italian (New Technologies for Cervical Cancer: NTCC) population-based randomized controlled screening trials the age- and type-specific distribution of incident hrHPV infections detected at the next screening round was assessed. HPV types were grouped into vaccine (bivalent: HPV16/18; polyvalent HPV16/18/31/33/45/52/58) and nonvaccine types.The incidence of screen-detected hrHPV among women ages 29 to 56 years was 2.54% (95% confidence interval, 2.30-2.78) in POBASCAM and 2.77% (2.36-3.19) in NTCC. In both studies, the incidence of bivalent, polyvalent, and nonpolyvalent infections decreased with age (P < 0.0001). Among women with incident infection(s), vaccine-type positivity changed quadratically with age, in particular for the polyvalent vaccine (P values: POBASCAM: bivalent 0.264, polyvalent 0.038; NTCC bivalent 0.039, polyvalent 0.005). However, more than 20% and 50% of women with incident hrHPV were positive for bivalent and polyvalent vaccine types, respectively, in all ages in both studies.We observed decreasing age trends of hrHPV vaccine and nonvaccine type incidences and age-related differences in the vaccine-type positivity among women with incident infections. Most importantly, hrHPV infections continued to be detected in all ages and the contribution of vaccine types remained substantial.Our results indicate a considerable reduction of new hrHPV infections in vaccinated cohorts, ensuing revision of screening guidelines.

Loading Center for Cancer Epidemiology and Prevention collaborators
Loading Center for Cancer Epidemiology and Prevention collaborators