Between 2001 and 2013, in all women who were 25–64 years old, 46.3% of CC were detected by a Pap smear (organized or spontaneous). The proportion of screening-detected CC in Italian-born women and in foreign-born women did not differ significantly (47.3 vs. 43.8%; P = 0.7).
Moreover, in the two groups of women with a preneoplastic lesion, there was a similar (P = 0.7) percentage who had participated in the regional prevention program (Table 3).
The APC models are shown in Figs 3 and 4. For CC, no considerable changes in period-specific incidence rate ratios (IRRs) were detected until around 2000, when there was a slight decrease, followed by an increase. Nevertheless, in recent years, the trend seems to be declining. An increase in cohort-specific IRRs was observed in women born after the 1950s, preceded by decreasing risks factors in the cohorts born in the first decades of the 20th century. A further decline was observed again in the younger cohorts born after 1970. Age-specific IRR continued to increase from the age of 25 years, flattening after 35–40 years and then slowly declining (Fig. 3).
Considering CIS, a strong increase in cohort-specific risks in subsequent generations was estimated, particularly in women born after 1970. A decline in period-specific IRR was observed after 2000, preceded by a growing trend. Age-specific IRRs flatten early and begin to fall after 35–40 years (Fig. 4).
We examined the trends in the incidence of cervical lesions over a 20-year period in Umbria, where an organized screening program has been in place since 1999.
For CC, a declining trend has been observed in women older than 65 years of age, whereas in the younger group it was stable. Conversely, we found a significant annual increase of 6.4% for CIS.
Our analysis has shown that in Italian-born women, the CC incidence is decreasing, whereas there has been a significant increase in cases diagnosed in immigrant women, especially in recent years. Furthermore, the foreign women, mainly from Central and Eastern European countries, tend to develop CC at a younger age.
As reported by several studies (Tornesello et al., 2014; Di Felice et al., 2015; Visioli et al., 2015), the high CC incidence in foreigners seems to be related both to the high prevalence of HPV infection and the low screening uptake in the immigration country.
At present, CC screening programs are restricted or ineffective in Central and Eastern European states, with several important obstacles, such as low coverage, high number of opportunistic smears, and the absence of follow-up of positive screened women. In addition, only a few countries have actually integrated the HPV vaccination into their national immunization program, mostly performed in local public health centers or school health services. HPV vaccination coverage therefore remains low because of poor acceptance and negative public reactions (Poljak et al., 2013). Indeed, the CC incidence rates in these countries are the highest in Europe and are expected to continue to increase (Vaccarella et al., 2016).
The absence of an organized program in the native country seems to affect the attitude of immigrant women to screening. A variety of sociodemographic and psychological factors can contribute toward the lower participation in screening among immigrants, such as language difficulties, high mobility, difficult working conditions, low perception of risk, and different cultural beliefs (Azerkan et al. 2012; Grandahl et al., 2015; Leinonen et al., 2017). Conversely, factors positively affecting participation in screening seem to include young age, good cultural level, a long stay in the host country, being married, and high income (Khadilkar and Chen, 2013; Grandahl et al.,2015).
High nonadherence rates were associated with a low socioeconomic status (Rondet et al., 2014, Leinonen et al., 2017) and, in turn, a low socioeconomic status appears to be linked to an increased risk of developing CC (Arnold et al., 2016; Fidler et al., 2016; Ginsburg et al., 2017).
Interestingly, our study showed that the percentage of lesions detected by screening in immigrant women is comparable to that of Italian-born women. In Italy, between 2009 and 2011, a relatively small difference in screening program adherence was found between Italian-born and foreign-born women (46.9 vs. 42.2%) (GISCI. Survey GISCI sulle migranti nei programmi di screening cervicale, 2014). Indeed, the participation of immigrant women seems to be similar to that of Italians during the reproductive age as, in this period of life, women have more contact with health services and healthcare staff, particularly because of pregnancies (Campari et al., 2016).
The increase in the incidence of CC in foreigners can also be explained partly by the high prevalence of HPV infections in their countries of origin. For example, in Romania, a country with high prevalence rates of HPV infection, CC is the first cause of cancer death in women aged between 15 and 44 years, and an infection with a high-risk HPV type is found in about 89% of cases (Pirtea et al., 2016). Di Felice et al. (2015) recently reported a higher risk of cervical lesions in women born in high HPV prevalence countries compared with Italian women, confirming that HPV prevalence in the country of origin is a major determinant for the onset of CC.
The age effect shown in our analysis, with upward age-specific IRR until 35–40 years and then slowly declining, was probably influenced by screening activity. The age at diagnosis for CC is related to several factors, such as the age at exposure to HPV, the latency between virus exposure and dysplasia, the immune status, sexual hormones, and the implementation of a screening program. In countries with poor or no screening, the incidence rapidly increases until the premenopausal period, at around 45 years. Conversely, in screened populations, CC incidence rates peak at ~35 years, when the positive effect of removal of precancerous lesions can be observed. However, in both unscreened and screened populations, the CC incidence is approximately constant after the age of 45 years, unless age-specific rates are further distorted by a different effectiveness of screening programs within various periods and cohorts (e.g. a lower uptake in older cohorts) (Vaccarella et al., 2013).
In addition, we observed a progressive decrease in CC risk in the cohorts born in the first decades of the 20th century and the younger cohorts, whereas in women born between 1950 and 1970 a growing risk emerged.
The declining cohort effects in older generations are probably because of improved prevention awareness and increased access to healthcare. However, after the Second World War, many aspects of sexual behavior, including earlier age at first sexual intercourse and multiple lifetime partners, have changed considerably, resulting in a progressive increase in the risk of HPV exposure. Also, several European countries and Japan showed similar increases in CC incidence rates following previous decreases among older generations (Vaccarella et al., 2013).
Interestingly, according to estimated period effects, in our study, a first short beneficial impact of screening seemed to have emerged in the early 2000s, immediately counteracted by the changes in the composition of society, with a progressive increase in the foreign population, which has led to the inversion of the positive trend. However, in recent years, there has been a new decrease in the CC risk, probably because of the increasing adherence to screening by immigrant women.
The favorable effect of screening in preventing the increase in CC risk among the youngest birth cohorts is evident in the Nordic countries, such as Denmark and Finland, where organized screening programs have been in place for a long period and decreases of the formerly high incidence rates were driven by period-specific decreases. Conversely, Central and Eastern European countries did not show any favorable period effect, which likely reflects the lack of adequate screening activities (Vaccarella et al., 2013, 2014).
The sharp increase in preneoplastic lesions emerging from our analysis has been observed in other countries, such as Denmark (Baldur-Felskov et al., 2015; Holst et al., 2016) and the Netherlands (Rozemeijer et al., 2015). This growth in rates is probably related to several factors, including an increased risk of contracting HPV infection because of a higher number of risk factors (e.g. multiple lifetime sexual partners, young age at first sexual intercourse, multi-parity, and oral contraceptive use) and a gradual improvement in diagnostic techniques. Nevertheless, excess use of cervical cytological examinations could also have contributed toward the increase in CIN III rates.
This study has some limitations. First, we used the country of birth for the definition of immigrant status. Precisely, Italian women (according to citizenship) who were born in a foreign country were classified as immigrants, even though the number of such women is presumably rather exiguous.
Second, given the small number of foreign-born women, we did not carry out the APC analysis by categorizing the Umbrian population by nationality. Finally, educational level, socioeconomic factors, or years since immigration are important variables related to participation in screening; hence, efforts to further investigate these factors are on-going for future analyses.
In conclusion, organized screening is the key intervention to prevent CC in our study. Immigration from countries with a high incidence of HPV infections and with poor implementation of preventive policies concealed favorable incidence trends among Italian women. Therefore, it is important to analyze CC trends by ethnicity. We found an increasing incidence of cervical lesions among immigrants from high-risk countries. This trend was associated at least partly with screening participation of immigrant women. The prophylactic vaccination against HPV, offered in Italy since 2008 to all females born since 1996, could contribute considerably toward cancer prevention in the coming years.
This work was supported by the Department of Health, Regional Government of Umbria.
Conflicts of interest
There are no conflicts of interest.
AIOM, AIRTUM.I numeri del cancro in Italia. Il Pensioro Scientifico Editore, 2016. 2016
Arnold M, Rentería E, Conway DI, Bray F, Van Ourti T, Soerjomataram I. Inequalities
in cancer incidence and mortality across medium to highly developed countries in the twenty-first century. Cancer Causes Control. 2016; 27:999–1007
Azerkan F, Sparén P, Sandin S, Tillgren P, Faxelid E, Zendehdel K. Cervical screening
participation and risk among Swedish-born and immigrant women in Sweden. Int J Cancer. 2012; 130:937–947
Baldur-Felskov B, Munk C, Nielsen TS, Dehlendorff C, Kirschner B, Junge J, Kjaer SK. Trends in the incidence of cervical cancer
and severe precancerous lesions in Denmark, 1997–2012 Cancer Causes Control. 2015; 26:1105–1116
Bray F, Lortet-Tieulent J, Znaor A, Brotons M, Poljak M, Arbyn M. Patterns and trends in human papillomavirus-related diseases in Central and Eastern Europe and Central Asia. Vaccine. 2013; 31Suppl 7H32–H45
Bruni L, Diaz M, Castellsague X, Ferrer E, Bosch FX, de Sanjosé S. Cervical human papillomavirus prevalence in 5 continents: meta-analysis of 1 million women with normal cytological findings. J Infect Dis. 2010; 202:1789–1799
Campari C, Fedato C, Iossa A, Petrelli A, Zorzi M, Anghinoni E, et al. Cervical cancer screening
in immigrant women in Italy: a survey on participation, cytology and histology results. Eur J Cancer Prev. 2016; 25:321–328
Clayton D, Schifflers E. Models for temporal variation in cancer rates. II: age–period–cohort
models. Stat Med. 1987; 6:469–481
Di Felice E, Caroli S, Paterlini L, Campari C, Prandi S, Giorgi Rossi P. Cervical cancer
epidemiology in foreign women in Northern Italy: role of human papillomavirus prevalence in country of origin. Eur J Cancer Prev. 2015; 24:223–230
Fidler MM, Soerjomataram I, Bray F. A global view on cancer incidence and national levels of the human development index. Int J Cancer. 2016; 139:2436–2446
Ginsburg O, Bray F, Coleman MP, Vanderpuye V, Eniu A, Kotha SR, et al. The global burden of women’s cancers: a grand challenge in global health. Lancet. 2017; 389:847–860
Gli stranieri in Italia: analisi dei dati censuari. 14° Censimento generale della popolazione e delle abitazioni. 21 October 2001. 2006
Grandahl M, Tyden T, Gottvall M, Westerling R, Oscarsson M. Immigrant women’s experiences and views on the prevention of cervical cancer
: a qualitative study. Health Expect. 2015; 18:344–354
Holst S, Wohlfahrt J, Kjær SK, Kamper-Jørgensen M, Kern P, Andersson M, et al. Cervical cancer screening
in Greenland, 1997–2011: screening
coverage and trends in the incidence of high-grade cervical lesions. Gynecol Oncol. 2016; 143:307–312
Khadilkar A, Chen Y. Rate of cervical cancer screening
associated with Immigration
status and number of years since immigration
in Ontario, Canada. J Immig Minor Health. 2013; 15:244–248
Kim HJ, Fay M, Feuer EJ, Midthune DN. Permutation tests for joinpoint regression with applications to cancer rates. Stat Med. 2000; 19:335–351
Leinonen MK, Campbell S, Klungsøyr O, Lönnberg S, Hansen BT, Nygård M. Personal and provider level factors influence participation to cervical cancer screening
: a retrospective register-based study of 1.3 million women in Norway. Prev Med. 2017; 94:31–39
Pirtea L, Grigoraş D, Matusz P, Pirtea M, Moleriu L, Tudor A, et al. Age and HPV type as risk factors for HPV persistence after loop excision in patients with high grade cervical lesions: an observational study. BMC Surg. 2016; 16:70
Poljak M, Seme K, Maver P, Kocjan BJ, Cuschieri KS, Rogovskaya SI, et al. Human papillomavirus prevalence and type-distribution, cervical cancer screening
practices and current status of vaccination implementation in Central and Eastern Europe. Vaccine. 2013; 31Suppl 7H59–H70
Rondet C, Lapostolle A, Soler M, Grillo F, Parizot I, Chauvin P. Are immigrants and nationals born to immigrants at higher risk for delayed or no lifetime breast and cervical cancer screening
? The results from a population-based survey in Paris metropolitan area in 2010 PLoS One. 2014; 22:e87046
Rozemeijer K, van Kemenade FJ, Penning C, Matthijsse SM, Naber SK, van Rosmalen J, et al. Exploring the trend of increased cervical intraepithelial neoplasia detection rates in the Netherlands. J Med Screen. 2015; 22:144–150
Rutherford MJ, Lambert PC, Thompson JR. Age–period–cohort
modeling. Stata J. 2010; 10:606–627
Sharma M, Bruni L, Diaz M, Castellsague X, de Sanjose S, Bosch FX, Kim JJ. Using HPV prevalence to predict cervical cancer
incidence. Int J Cancer. 2013; 132:1895–1900
Tornesello ML, Giorgi Rossi P, Buonaguro L, Buonaguro FM; HPV Prevalence Italian Working Group. Human papillomavirus infection and cervical neoplasia among migrant women living in Italy. Front Oncol. 2014; 4:31
Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012 CA Cancer J Clin. 2015; 65:87–108
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; 49:3262–3273
Vaccarella S, Franceschi S, Engholm G, Lönnberg S, Khan S, Bray F. 50 years of screening
in the Nordic countries: quantifying the effects on cervical cancer
incidence. Br J Cancer. 2014; 111:965–969
Vaccarella S, Franceschi S, Zaridze D, Poljak M, Veerus P, Plummer M, et al. Preventable fractions of cervical cancer
via effective screening
in six Baltic, central, and eastern European countries 2017–40: a population-based study. Lancet Oncol. 2016; 17:1445–1452
Visioli CB, Crocetti E, Zappa M, Iossa A, Andersson KL, Bulgaresi P, et al. Participation and risk of high grade cytological lesions among immigrants and Italian-born women in an organized cervical cancer screening
program in Central Italy. J Immigr Minor Health. 2015; 17:670–678
Wang D. Confidence intervals for the ratio of two binomial proportions by Koopman’s method. Stata Technical Bulletin. 2000; 58:16–19
Zhang NR, Siegmund DO. A modified Bayes information criterion with applications to the analysis of comparative genomic hybridization data. Biometrics. 2007; 63:22–32
Keywords:Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
Age–Period–Cohort; carcinoma in situ; cervical cancer; cervical dysplasia; human papilloma virus; immigration; inequalities; screening