Cancer screenings

Key points

• The decision to start screening is based on adequate knowledge of the significance of the cancer being screened, the early detection methods, as well as the treatability and effectiveness.
• Cervical and breast cancers are currently screened in Finland. In addition, some municipalities have initiated voluntary colorectal cancer screening.
• Screening for other cancers has been studied, too, but there is not yet sufficient evidence of feasible screening tests and their effectiveness.

Cancer screening is the systematic identification and management of precancerous lesions or early stage cancers within the population. The main objective is to reduce mortality due to the cancer being screened. In addition, the aim is to reduce the incidence of invasive cancers, if their development can be avoided by treating the precancerous lesions. Detection of precancerous lesions or cancer in its early stage shortens treatment durations and reduces the need for demanding therapies, which reduces the burden of treatment as well as costs.

However, in addition to benefits there may also be disadvantages related to screening. False screening results may lead to unnecessary referrals and further examinations, and on the other hand malignant tumors can remain undetected. Screening can also find tumors that would have not resulted in the death of a person in their lifetime. It is therefore important that the benefits and harms of screening are kept in balance through careful operations, regular monitoring, and evaluation.

Before initiating screening sufficient knowledge is needed of the importance of the cancer being screened, the early detection methods, as well as the treatability of the cancer and effectiveness of screening. Finnish cancer screening programs have been launched on the basis of scientific evidence, and are regulated by e.g. the Health Care Act and Governmental Decree of Screenings.

Governmental Decree of Screenings obligates the municipalities in Finland to provide free of charge cervical cancer screening every five years for women between 30–60 years of age, and breast cancer screening once every 20 to 26 months for women between 50–69 years of age. In addition to these screening programs some municipalities have initiated voluntarily colorectal cancer screening every two years for men and women of 60–69 years of age.

Municipalities choose the screening service provider and invite the target population to the screening test with a personal invitation letter. If a test gives rise for concern person is  referred to further examinations and, if indicated, proceeded to further management.

Information collected from the different stages of the screening process is provided to the Mass Screening Registry which is the part of the Finnish Cancer Registry . Centralized registration of screening data is based on the Personal Data Act, as well as the law and decree of health care’s nationwide personal records. Using the registry information, the Mass Screening Registry will monitor and evaluate the quality and impact of screening on mortality and publishes annual screening statistics. [1]

_{Figure 1. Cervical cancer incidence by age group in 1961, 1991 and 2013. Cervical cancer screening was initiated in 1963, and was extended to whole Finland in early 1970s.}

Cervical cancer screening

Precancerous cervical lesions can be microscopically detected and treated so that it does not develop into cancer. Cervical cancer screening is carried out with a gynecological Pap smear or an HPV test. If an HPV test is used as the primary method, positive results lead to a subsequent Pap smear test to assess the need for further actions. If the outcome of the Pap smear indicates a referral to further examination, a cervical tissue sample will be taken in colposcopy and analyzed by histopathology. If a precancerous lesion is found, the transformational zone tissue is removed. [2] In most cases, the procedure is done at an outpatient clinic. If cancer is found in the tissue sample, the patient will be referred for treatment at an oncology clinic.

The cervical cancer screening program in Finland was launched in the early 1960s. Due to screening, cervical cancer has become rare (Figure 1) and mortality caused by it has been reduced to about one fifth of the starting level. Screening has led to avoiding more than 250 deaths caused by cervical cancer, and about 500–1 000 cervical cancer cases every year. [3]

Every year, approximately 250 000 women aged 30–60 years are invited to screening, mainly done with a Pap smear test. In some municipalities, also women aged 25 or 65 are invited. About 1% of participants will be referred to further examination i.e. colposcopy and biopsies. In addition, about 5% of the participants are re-called for the follow-up test before the next screening invitation.

One challenge with the cervical cancer screening program has been the low participation rate: in the 2000s, only somewhat less than 70% of those invited have participated in the screening. Women under the age of 40 have participated particularly poorly (Figure 2). However, good invitation practices can improve the participating activity of all ages. It is essential that the invitation letter offers a time and place for the test which the woman may easily change; and that a re-invitation is sent to women who did not participate in the screening after the first invitation. [4, 5] Participation has also been improved by the possibility of taking the screening sample at home. This possibility can be offered as a second re-invitation. [4, 5]

The proportion of women for whom a follow-up test is recommended or a referral to further examinations provided vary regionally. Although the variations are not directly reflected in cervical cancer incidence [6], there is a need to improve the quality of screening diagnostics in Finland and ensure the quality of screening in a more systematic way.

Also, the screening of over 60-year-olds reduces the incidence and mortality of cervical cancer. [7] Thus, expanding the screening program to even older age groups is under consideration. In addition, it must be ensured that women who have been previously diagnosed with a precancerous lesion or to whom a follow-up test have been recommended, are regularly followed after the screening program ends.

The most important factors contributing to the development of cervical cancer are human papilloma virus (HPV) infections and tobacco smoking. Young people usually receive the HPV-infection soon after the start of their sexual activity. However, the majority of the infections heal spontaneously. If an HPV infection remains persistent, it may eventually develop into cervical or other anogenital cancerous lesion.

In 2013, a vaccination against HPV as part of the vaccine program was initiated in Finland. HPV vaccination is given to girls 12 years of age (at first it was given to 13–15-year-olds) in school health services. It is essential that the vaccination is given to young people who have not been exposed to HPV yet.

The vaccination program aims in reducing the prevalence of HPV-viruses and related diseases also within the screening program’s target population. So far, however, vaccination has not reduced the need for screening to prevent cervical cancer in our country.

_{Figure 2. Participation in cervical cancer screening by age group in 1991–2012}.

Breast cancer screening

Breast cancer has been the most common cancer in women since the 1960s, and today its share of women’s cancers is as high as 30%. Initiating screening has been one reason for the growth of breast cancer incidence but also the risk factors for breast cancer have become more common.  (see Cancer risks and protective factors (Figure 3).

Breast cancer screening is performed by mammography, i.e. X-ray examination in which breast images are taken from two directions. If the mammography finding is abnormal, the woman is recalledto further assessments at the screening center. If these (the additional mammography, ultrasound and needle biopsy study) cannot rule out the possibility of cancer, examinations continue at a hospital and a breast biopsy is taken to find out the malignancy of the tumor.

Finland was the first country in the world to start a nationwide organized screening for breast cancer in 1987. Every two years, a personal invitation letter is sent to women in the target age  to participate in the screening. Breast cancer screening has expanded to women from 50 to 69 years of age by 2016. The performance of the program, as well as the benefits and harms are already being evaluated in this age group.

Approximately 83% of the women invited take part in the screening. Less than 3% of the participants are recalled to further assessments, and breast cancer is found in one of every five of them. About two-thirds of breast cancers are screen-detected in those invited to screening. [8]

The impact of screening on breast cancer mortality has been studied since the 1990s. In the period of 1992–2003 the breast cancer mortality in the invited women was 22% lower compared to the situation, had the screening not taken place. Breast cancer mortality of women participating in screening was 28% lower than in the absence of screening. [9]

Due to more effective treatments, deaths from breast cancer have decreased in the 2000s also in younger women below the target age group of screening. [10] At the same time, participation in screening has decreased, and it varies between hospital districts. [11] In spite of these factors, the impact of screening on breast cancer mortality has not changed while entering the 2010s, so breast cancer screening is still effective in Finland. [12]

In addition to the benefits of breast cancer screening there are also harms. Approximately one in five women participating in screening regularly in the age of 50–69 is unnecessarily sent to referral examination at least once. [13] Also, small early stage tumors are found, some of which would not have caused symptoms during the woman’s lifetime. This most serious harm of breast cancer screening causes at most  every tenth tumor in breast. [14–16]

_{Figure 3. Breast cancer incidence by age group in 1962, 1992 and 2013. Breast cancer screening was initiated gradually in 1987 and was extended to whole Finland in the early 1990s.}

Colorectal cancer screening

Colorectal cancer is the third most common cancer in Finland. Early symptoms of colorectal cancer are often vague, so seeking diagnosis is easily postponed. Colorectal cancer is therefore often found at a late stage when it has already spread and is difficult to cure.

According to international studies, colorectal cancer screening reduces mortality regardless of primary test used i.e., a fecal occult blood test or sigmoidoscopy. [17, 18] The use of the fecal blood test is based on the fact that intestinal tumors bleed more frequently than healthy mucosa.

However, on the basis of evidence it is not yet clear whether colorectal cancer screening is adaptable in Finnish health care and what screening practice is optimal. Therefore, in Finland in 2004 a colorectal cancer screening was launched in a randomized setting in which half of the target population of the screening, i.e. 60–69-year-old men and women were invited to screening and the other half was left as a control group who did not receive invitation. [19] A guaiac-based fecal occult blood test (gFOBT) was used as a screening test.

The number of municipalities voluntarily participating in screening has grown over the years. In 2014, 170 municipalities participated in screening which covered nearly half of the target population. About 70% of those invited to screening have participated, i.e. sent the fecal sample by mail to the screening laboratory in Tampere. [20] Three out of one hundred participants were referred to examination, i.e. colonoscopy. Cancers or advanced adenomas have been found in around every tenth sent to endoscopy.

In 2015, an interim report was published, in which the effect of screening on colorectal cancer mortality was studied. In this study, evidence of a difference in colorectal cancer mortality between those invited to the screening and uninvited controls was not yet found. [21] As the follow-up time in both groups had only been a few years, follow-up still needs to continue before the effect of screening with gFOBT on colorectal cancer mortality in Finland is confirmed.

Screenings of other types of cancers

Prostate cancer is the most common cancer in Finnish men. Finland has participated in the European randomized screening trial, according to which screening with the PSA-test can reduce prostate cancer mortality by a fifth. [22] Screening for prostate cancer, however, is not recommended at the population level, because benign prostate tumors cannot often be distinguished from malignant, aggressively advancing tumors. In addition, prostate cancer treatment can cause long-term harm, such as urinary incontinence, erectile difficulty or rectal irritation.

Lung cancer is the most common cause of cancer death for men. Computed tomography screening for smokers reduces lung cancer mortality one-fifth compared to X-ray imaging. [23] Screening for lung cancer is not recommended as a screening test is not yet as adequate as it should, and too many small harmless nodes are found in screening.

The impact of screening on ovarian cancer mortality has been studied in two large, randomized trials [24-25], one of which suggested some indications of its effectiveness.

Also, for example, screening for gastric cancer has been considered [26-27], but there is not yet sufficient evidence of an adequate screening test and its effectiveness.

 

Literature

_{[1] Statistics from the Mass Screening Registry.} 

_{[2] Kohdunkaulan, emättimen ja ulkosynnytinten solumuutokset [online document]. Current Care guideline. The Finnish Medical Society Duodecim and the Finnish Colposcopy Association’s working group. Helsinki: The Finnish Medical Society Duodecim 2010 [published 14.6.2010]. www.kaypahoito.fi.}

_{[3] Hristova L, Hakama M. Effect of screening for cancer in the Nordic countries on deaths, costs and quality of life up to the year 2017. Acta Oncologica 1997; 36 (Suppl 9): 1–60.}

_{[4] Virtanen A, Anttila A, Luostarinen T, Nieminen P. Self-sampling vs. reminder letter: effects on cervical cancer screening attendance and coverage in Finland. Int J Cancer 2011; 128: 2681–7.}

_{[5] Virtanen A, Anttila A, Luostarinen T, Malila N, Nieminen P. Improving cervical cancer screening attendance in Finland. Int J Cancer 2015; 136(6): E677–84. [DIRECT LINK TO ONLINE MATERIAL doi: 10.1002/ijc.29176.]}

_{[6] Lönnberg A, Nieminen P, Kotaniemi-Talonen L ym. Large performance variation does not affect outcome in the Finnish cervical cancer screening programme. Cytopathology 2012; 23: 172–80. [DIRECT LINK TO ONLINE MATERIAL doi: 10.1111/j.1365-2303.2011.00849.x.]}

_{[7] Lönnberg S, Anttila A, Luostarinen T, Nieminen P. Age-specific effectiveness of the Finnish cervical cancer screening programme. Cancer Epidemiol Biomarkers Prev 2012; 21: 1354–61.}

_{[8] Sarkeala T, Luostarinen T, Dyba T, Anttila A. Breast carcinoma detection modes and death in a female population in relation to population-based mammography screening. SpringerPlus 2014; 3: 348.}

_{[9] Sarkeala, Heinävaara S, Anttila A. Organised mammography screening reduces breast cancer mortality: A cohort study from Finland. Int J Cancer 2008; 122: 164–9.}

_{[10] Autier P, Boniol M, La Vecchia C ym. Disparities in breast cancer mortality trends between 30 European countries: retrospective trend analysis of WHO mortality database. BMJ 2010; 341: c3620.}

_{[11] Sarkeala T, Näveri T, Malila M, Anttila A. Rintasyövän väestöseulonnan tunnusluvut 1990- ja 2000-luvuilla. Suom Lääkäril 2013; 68(4): 225–31.}

_{[12] Heinävaara S, Sarkeala T, Anttila A. Impact of organised mammography screening on breast cancer mortality in a case-control and cohort study. Br J Cancer 2016; 114: 1038–44. [DIRECT LINK TO ONLINE MATERIAL doi: 10.1038/bjc.2016.68]}

_{[13] Hofvind S, Ponti A, Patnick J et al. False-positive results in mammographic screening for breast cancer in Europe: a literature review and survey of service screening programmes. J Med Screen 2012; 19 (Suppl 1): 57–66.}

_{[14] Puliti D, Duffy SW, Miccinesi G et al. Overdiagnosis in mammographic screening for breast cancer in Europe: a literature review. J Med Screen 2012; 19 (Suppl 1): 42–56.}

_{[15] Heinävaara S, Sarkeala T, Anttila A. Overdiagnosis due to breast cancer screening: updated estimates of the Helsinki service study in Finland. Br J Cancer 2014; 111(7): 1463–8. [DIRECT LINK TO ONLINE MATERIAL doi: 10.1038/bjc.2014.413.]}

_{[16] Parvinen I, Heinävaara S, Anttila A, Helenius H, Klemi P, Pylkkänen L. Mammography screening in three Finnish residential areas: comprehensive population-based study of breast cancer incidence and incidence-based mortality 1976-2009. Br J Cancer 2015; 112(5): 918–24. [DIRECT LINK TO ONLINE MATERIAL doi: 10.1038/bjc.2014.642.]}

_{[17] Hewitson P, Glasziou P, Irwig L, Towler B, Watson E. Screening for colorectal cancer using the fecal occult blood test, Hemoccult. Cochrane Database Syst Rev 2007; CD001216.}

_{[18] Segnan N, Armaroli P, Bonelli L et al. Once-only sigmoidoscopy in colorectal cancer screening: follow-up findings of the Italian Randomized Controlled Trial – SCORE. J Natl Cancer Inst 2011; 103: 1310–22.}

_{[19] Malila N, Anttila A, Hakama M. Colorectal cancer screening in Finland: details of the national screening programme implemented in Autumn 2004. J Med Screen 2005; 12: 28–32.}

_{[20] Malila M, Oivanen T, Malminiemi O, Hakama M. Test, episode, and programme sensitivities of screening for colorectal cancer as a public health policy in Finland: an experimental design. BMJ 2008; 337: 1342–4.}

_{[21] Pitkäniemi J, Seppä K, Hakama M et al. Effectiveness of screening for colorectal cancer with a fecal occult-blood test, in Finland. BMJ Open Gastro 2015; 2: e000034.}

_{[22] Schröder F, Hugosson J, Roobol MJ et al. Screening and prostate cancer mortality: results of the European Randomised Study of Screening for Prostate Cancer (ERSPC) at 13 years of follow-up. Lancet 2014; 384(9959): 2027–35.}

_{[23] The National Lung Screening Trial Research Team: Reduced Lung-Cancer Mortality with Low-Dose Computed Tomographic Screening. N Engl J Med 2011; 365: 395–409.}

_{[24] Buys SS, Partridge E, Black A et al. Effect of screening on ovarian cancer mortality: the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Controlled Trial. JAMA 2011; 305(22): 2295–303. [DIRECT LINK TO ONLINE MATERIAL doi: 10.1001/jama.2011.766.]}

_{[25] Jacobs IJ, Menon U, Ryan A et al. Ovarian cancer screening and mortality in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a randomized controlled trial. Lancet 2016; 387(10022): 945–56. [DIRECT LINK TO ONLINE MATERIAL doi: 10.1016/S0140-6736(15)01224-6.]}

_{[26] IARC Helicobacter pylori Working Group. Helicobacter pylori Eradication as a Strategy for Preventing Gastric Cancer. IARC Working Group Reports No. 8. Lyon: International Agency for Research on Cancer 2014. [DIRECT LINK TO ONLINE MATERIAL http://www.iarc.fr/en/publications/pdfsonline/ wrk/wrk8/index.php]}

_{[27] Pasechnikov V, Chukov S, Fedorov E, Kikuste I, Leja M. Gastric cancer: Prevention, screening and early diagnosis. World J Gastroenterol 2014; 20: 13842–62.}