Screening of cervical cancer

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Cervical cancer is the third most common cause of female mortality worldwide, with the mortality rate 10 times higher in developing countries, and 80% of new cases occuring in these regions, compared to the developed countries (Ferlay, 2010; Haie-Meder, 2010). This disparity is in connection with low level of knowledge about unsafe sex and inaccessibility to screening and treatment programs, for women in developing countries (Ferlay, 2010; WHO, 2009). The main problem, in developed countries, is still insufficient coverage of women in the generative age with the screening test (Commission of the European Union, 2007; Haie-Meder, 2010).

Cervical cytology based on Pap smears remains the cornerstone of cervical cancer prevention programs, although this filed has rapidly been developing due to improved understanding of the natural history of the disease and technology innovations, such as liquid-based cytology, automated interpretation of Pap smears and testing for human papillomaviruses (HPVs) (American Cancer Society Guidelines, 2011; ESMO European guidelines for quality assurance, 2010). This, on the one hand, points up the neccessity for establishing the uniform indicators for monitoring program performance, to enable data comparison across the countries, and on the other hand - leads to fast exchanges of practice guidelines (Table 4) (ESMO European guidelines for quality assurance, 2010).

It is now well known that a persistent infection with sexually transmittable human papillomaviruses is responsible for virtually all cases of cervical cancer (Haie-Meder, 2010). Early age at first sexual intercourse and early pregnancies have been recognised as risk factors. The evidence linking HPV infection to cervical cancer has initiated the development of HPV DNA testing, to support more accurate risk stratification, beyond the capacity of conventional Papanicolaou smear testing (Figure 2) (American Cancer Society Guidelines, 2011; ESMO European guidelines for quality assurance, 2010). Also, primary prevention by prophylactic vaccination against the HPV types that are causally linked with most cervical cancers in Europe, HPV-16 and HPV-18, is now commercially available (Schiller & Lowy, 2010). The high efficacy of the vaccines is expected to dramatically decrease cervical cancer, by preventing up to 70% of newly diagnosed cases. However, prophylactic vaccination is performed in young girls and it will take a time until it provides the health gains. Therefore, cervical screening still remains the main preventive option (Figure 2). Nowadays, situation is that the high cost of the vaccine prevents its widespread implementation, which may further increase the gap in cervical cancer statistics between developed and developing countries (Haie-Meder, 2010).



Future HPV Vaccine I.HPVTest 2. HPVTest

Fig. 2. Combined strategies to decrease cervical cancer 7.3 Screening of colorectal cancer

Cancers of the colon and rectum altogether are the third most common cancer type in the world and the most common newly diagnosed cancer in EU (Ferlay, 2010). In general, incidence is increasing along with industrialisation and urbanisation and is slightly higher in western and central, than in northern and southern and eastern Europe (Labianca, 2010).

Five-year survival rates, after the disease is detected, is much worse in the Eastern European countries, then in the developed countries (34%, compared to 54% and 65%, in the Western European countries and the USA, respectively) (Ferlay, 2010). As the result of the early detection programs implementation in many EU countries, in past decades, five-year survival rates show more favourable trends in all regions of Europe, compared to as it was before (Labianca, 2010).

Strong genetic influence can be attributed to only 5%-10% of colorectal cancers cases, due to either polyposis or non-polyposis syndromes, while the majority of cases occur sporadically (Balmana, 2010). The most important exogenous factors identified so far include: western-style diet and low physical activity, smoking tobacco and inflammatory bowel diseases, while the effect of chronic use of non-steroidal anti-inflammatory drugs for the prevention or regression of colorectal adenomas, has not yet been strongly confirmed (Labianca, 2010).

If take into account fact that a 10-35 years long-lasting period is needed for the transformation of benign adenomas to cancer, it seems reasonable to expect that the systematic implementation of the programs of active searching for subjects with localised cancer or pre-cancer lesions, could substantially reduce colorectal cancer mortality rate in population. It is estimated that under these conditions, colorectal cancer could reach a high cure rate of 80% and more (Winawer, 2003, as cited in Majnaric-Trtica, 2008b). This makes colorectal cancer an ideal candidate for screening. Since about 70% of patients are >65 y of age and the disease is rare under the age of 45 (2 per 100 000/ y), target groups for screening usually include population aged 50-74y, with the minimum recommendations for the age range 60-69y (American Cancer Society Guidelines, 2011; Labianca, 2010). In order to complement community-based screening programs for breast and cervical cancers, established in many EU countries several decades ago, the EU Commision set up in 2003 recommendations for early detection of colorectal cancer, and the action plan "Europe against Colon Cancer", based on "the Brussels Declaration" (IUCC/Interantional Union against cancer, 2007, WHO/WHO Cancer Control Strategy, 2005, as cited in Majnaric-Trtica, 2008b).

*Based on an uptake rate of 78%

Fig. 3. Predicted outcomes of screening on colorectal cancer (according to NHS.UK, 2011)

Up to date, two strategies have been available: faecal occult blood test (FOBT) and endoscopy (colonoscopy or proctosigmoidoscopy) (American Cancer Society Guidelines for the Early Detection of Cancer, 2007, BMJ Clin Evid Concise/Colorectal cancer screening, 2006, as cited in Majnaric-Trtica, 2008b; Labianca, 2010). Experiences on using the conventional screening method, the Faecal Occult Blood Test (FOBT), applied in asymptomatic population at average risk, showed that 3-5% subjects with positive results are to be expected (Winawer, 2003; Bond, 2006, as cited in Majnaric-Trtica, 2008b). The rationale for its use is based on the fact that, at an early stage, a colorectal tumour causes minor bleeding which can not be seen with the naked eye. The purpose of the screening is to check for this hidden blood in the stool sample. Recently introduced, the Faecal Immunochemical Test (FIT), has been shown as simpler for use and of a better specificity, however, because of higher price and the lack of efficiency analysis, it has not been yet widely implementated (American Cancer Society Guidelines, 2011). In most recommendations, the FOBT is used as a standard screening method, and a colonoscopy -for follow-up of test-positive cases. Based on widely obtained data, 10-15% of those subjects referred to colonoscopy are expected to be diagnosed as cancer and 30-40% as adenomas (Figure 3) (American Cancer Society Five-Year Relative Survival Rates, 2007, as cited in Majnaric-Trtica, 2008b; NHS.UK, 2011). Experiences until now showed that if screening strategies are implemented as organised programs based on the screening interval of 1-2 years, it is possible to reduce mortality rate for 18% -33% (Achkar, 2006, as cited in Majnaric-Trtica, 2008b).

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