Poblaciones genéticas

In most countries diagnosis of changes in the cervix is done with the use of traditional screening methods of molecular biology via cervical Papanicolaou test (Pap) (Everett et al., 2011). During the test some of the cervix tissue is removed with a special brush and checked under a microscope (Gheit et al., 2007; Gershenson and Ramirez, 2008). However, concerns have been raised on the low sensitivity of the conventional Pap test as its estimates vary greatly between studies (30%-87%). Specificity was found to range from 86% to 100% (Nanda et al., 2000; Sasieni et al., 1996; Agency for Healthcare Research and Quality, 2011). More sensitive HPV detection methods, such as the HPV DNA testing have been proposed to increase efficacy of cervical cancer screening programmes (Hong et al., 2009), however Poland is still using the Pap test as a screening method (Spaczyński et al., 2009).

Regular screening of all women at risk helps to detect those with an increased risk of developing an invasive cancer through an early treatment of pathological changes (NHS Cancer Screening Programmes, 2008). Cervical screening programmes including organised and opportunistic (i.e. screening of patients hospitalised for different reasons) types have been showed to decrease incidence and mortality from cervical cancer, and it has been previously observed that population based cancer screening initiatives tend to achieve higher attendance rates than those with opportunistic ones which might miss women at the highest risk of developing the disease (Anttila et al., 2009; Palencia et al., 2010; van der Aa et al., 2008). Numerous members of the European Union (e.g., Czech Republic, Estonia, others) either already have, or are in the process of introducing population-based cervical cancer screening programmes, but some of them need to improve the quality and coverage of screening (Anttila et al., 2009; van der Aa et al., 2008; OECD, 2012).

Benefits of population based nationwide cervical cancer programmes can be further supported by the example of screening in the UK, which prior to national rollout of its population based screening in 1988 was largely ineffective (Quinn et al., 1999; NHS Cancer Screening Programmes, 2008). At least two thirds of women with invasivecervical cancer had never been screened because most of the cytologicaltests were performed on women presenting for

gynaecological,obstetric, or contraceptive reasons (Quinn et al., 1999; NHS Cancer Screening Programmes, 2008). The current success of screening has been achieved partially due to the use of a call and recall system which helped to keep track of any follow-ups and, in case the results of the smear appear normal and such approach could be also considered in other countries (Buehler and Parsons, 1997; Torres-Mejia et al., 2000) as well as high (>80%) average coverage reaching approximately 80 per cent (NHS Cancer Screening Programmes, 2008). Additionally, the NHS screening system offered incentives in a form of payments to general practitioners and the first external quality assessment schemes for laboratories, resulting in great improvement of its performance (Quinn et al., 1999; NHS Cancer Screening Programmes, 2008). Currently, approximately 4,500 lives are saved each year (approximately 64 million to date) and around 75% of cancer cases are prevented in women who attend regularly (Sasieni et al., 2003; NHS Cervical Screening Programme, 2012). Sasieni et al. (2003) estimated that single negative smear in the UK in the years 1990-2001 offered substantial protection against cervical cancer equalling to 41% for 20-39 age group, 69% for women aged 55-69 years old who attended screening every 3 years (table 7) (Sasieni et al., 2003).

Table 7 Percentage of Preventable Cancer - Protection offered by a single negative smear in UK between 1990-2001 (Sasieni et al., 2003)

Screening interval group 20-39 years 40-54 years 55-69 years

3-yearly screening 41% 69% 73%

5-yearly screening 30% 63% 73%

Women aged between 25 and 64 are provided with targeted cervical screening tests free of charge every three to five years depending on their age (CRUK, 2009; NHS Cancer Screening Programmes, 2008). Although the lower screening age limit is 25, following the death of the UK–Big Brother television celebrity Jade Goody, who died in 2009 from cervical cancer, a heated national debate on lowering the cervical screening age began (Metcalfe et al., 2011). However, there are frequent false positives, and low incidence rates of this cancer in women younger than 25 years old and therefore no extended screening is indicated for that age group (CRUK, 2009).

Similarly, Finland introduced an organised cervical screening programme (with a 5-year screening interval) in 1963 and extended it to the whole country by the 1970s. From the early 70s coverage exceeded 80%, later reaching 90% (i.e. at least 1 smear made per female) and 98% of women had been screened at least once in their lifetime (Van der Aa et al., 2008). The introduction of this programme resulted in a 50% reduction in cervical cancer mortality by the early 70s later reaching about 80% decrease in both mortality and age-adjusted mortality (Anttila and Nieminen, 2007).

In Poland, the national cervical cancer screening programme was introduced in 2006 in response to an unfavourable epidemiologic situation, as approximately half of women diagnosed with cervical cancer would die from it (Spaczyński et al., 2010). Prior to the national rollout, cervical cancer screening was scarce, opportunistic, and restricted to only small mostly urban districts (Bardin et al., 2008).

Following the Council of the European Union recommendations (Council of the European Union, 2003) the Polish Ministry of Health, with the National Health Fund of Poland and the Polish Gynaecological Society, developed a National Population Based Cervical Cancer Screening Programme targeting (by postal invitation) women aged 25 to 59 to be invited for screening (Bardin et al., 2008; Spaczyński et al., 2010). In the first few years of the programme (2007-2009) a slow increase in rates of screened women was observed. In 2007, the first year of the national rollout, 21.3% of eligible women were tested, in 2008 there were 24.4% and in 2009 over 26.8% of women undertook the cervical cancer screening (Spaczyński et al., 2010). This means that the programme was still far behind countries with long history of population based screening (i.e. UK or Finland, please refer to table 8 below).

Table 8 Comparison of the main features of cervical cancer screening programmes in Poland, UK and Finland

Age of target population Screening location Screening procedures Screening

personnel Uptake rates

Poland

25–59– screened every 3 years (or more frequently); <25 or > 59 on request. Gynaecology clinic Liquid based cytology Gynaecologist 2007–21.25% † 2008–24.39% † 2009–26.77% † 2009–76.7% (uptake ever) € UK 25–49 – every 3 years; 50–64 – every 5 years. Patient's local general practice Liquid based cytology Nurse or physician 2008/9 –78.6%‡ Finland 30-60 - every 5-years Patient's local health care centres Liquid based cytology Trained nurses (midwives) 2004–72% (90% including additional opportunistic screening) ¥

†(Spaczyński et al., 2010); ‡(NHS, 2009);¥(Van der Aa et al., 2008); €(Central Statistical Office of Poland, 2012c)

Poland and other Eastern European countries introducing screening could draw from experiences of countries with much greater screening experience (Holland et al., 2006) by learning from the positive and negative experiences. For example, as mentioned previously it has been demonstrated that call-recall system improved the screening uptake in the UK.

Currently, cervical cancer screening in Poland is always conducted in public or private gynaecology clinics and is accessible to women without a referral, cost free, from their general practitioner (Narodowy Fundusz Zdrowia (NFZ), 2011a) (see Appendix 1 for programme information leaflet). Women aged 25-59 who have not had a cytology conducted within 3 years receive a postal screening invitation with a proposed appointment date or alternatively they can go to their gynaecologist directly and request for a test. Women from high risk groups (HIV, HPV, immunosuppressed etc.) that may be more prone to developing cervical lesions might be advised by their physician to attend cytology every 12 months (NFZ, 2011a) (for description of viral and immunosupression risk factors see section 2.4.2.3). Women who are outside the screening recommended age range can also undergo cost free cervical screening through a referral from their gynaecologist (NFZ, 2011a).

In 2008, after the role of HPV in the formation of cervical cancer was demonstrated by Nobel Prize Laureate Harald zur Hausen, a prophylactic vaccine against several of the most

aggressive strains was developed (Mocarska et al., 2012). Currently, two HPV vaccines exist: Cervarix (produced by GlaxoSmithKline) and Gardasil (produced by Merck) (CDC, 2012b). These vaccines are made of HPV‐like particles that are non‐infectious and offer a new way of the cervical cancer prevention (CDC, 2012b; Mocarska et al., 2012). Both of these vaccines protect against two HPV types: 16 and 18 most commonly associated with cancers of cervix, vulva, vagina, penis, anus and oropharynx (Khalid et al., 2011). Gardasil additionally covers types 6 and 11 (CDC, 2012b). CDC (2012) highlighted that HPV vaccine is a strong preventative measure and it is safe and in protecting both women and men the most common HPV types (CDC, 2012b). Both vaccines are currently available in Poland (Gardasil is registered under name of Silgard) (Mocarska et al., 2012) but none of them is on the list of refunded medicinal products (Dziennik Urzędowy Ministra Zdrowia, 2012).

While these vaccines give hope for reducing cervical cancer incidence there is a growing controversy around this new method because of the numerous reports of complications associated with those vaccines (Mocarska et al., 2012) such as pain, bruising, swelling at the injection site and fainting (Brankovic et al., 2013) and in some cases suspected serious disabilities or death (Tomljenovic et al., 2013). Irrespective of the creation of the vaccine, there is need for effective screening methods as the vaccine does not work for all HPV types and does not cover women prior to exposure to the virus (CDC, 2012a). Vaccine therefore will not eradicate the disease, but merely decrease its extent in the population (Garland, 2009) and the effective population based screening programmes are needed, especially in countries with high mortality from cervical cancer such as Poland and other countries in Eastern Europe (WHO, 2010).