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Cervical Cancer: Global Prevalence and Mortality


What is cervical cancer?

Cervical cancer, or cancer of the cervix uteri, is a malignant growth or tumor that originates as abnormal cells in the cervical opening into the uterus (the os) which, if left untreated, progresses over time in different stages to the rest of the cervix, the uterus and reproductive system and eventually metastasizes to other organs of the body, including the brain. Approximately 99.7% of invasive cervical cancers are caused by the human papilloma virus (HPV), a sexually transmitted virus (Walboomer 1999). In fact, HPV has been deemed the first ever necessary cause of a human cancer; that is cervical cancer does not and will not develop in the absence of persistent HPV DNA (Bosch 2002). The main HPV subtypes that cause about 95% of cervical cancers are 16, 18, 45, 31, 33, 52, 58, and 35 with 16 and 18 being the most prevalent (58.9% and 15% respectively) worldwide (Munoz 2003). The time for progression of cervical cancer from precancerous cells to full blown invasive cancer can take about 10-15 years (ARPH 2016), hence if regular screening is performed, it can be caught in early precancerous stages and treated.


What is the prevalence across the globe and what are disparities in prevalence?

Over the past 40 years, the rate of incidence and mortality of cervical cancer has decreased drastically in high income countries whereas low and middle-income countries (LMICs) have shown constant and in some cases increasing trends (Vaccarella 2013). Annually, over 500,000 women are diagnosed, causing over 270,000 deaths recorded with more than 75% of cases occurring in Africa and India (Parkin 2005). The World Health Organization (WHO) estimates that currently 88% of worldwide invasive cervical carcinoma (ICC) mortalities occur in LMICs (Ferlay 2015), and this rate is expected to increase to 98% by 2030, furthering the disparities (ACCP 2011) as the total number of annual worldwide mortalities increases to nearly 400,000 (GLOBOCAN 2012). It is worthy to note that these numbers in LMICs do not include deaths from cervical cancer which go undetected.


How is it currently diagnosed and treated in various settings?

For cervical cancer diagnoses and treatment in higher resource settings, the WHO recommends a three tiered approach (WHO 2013). This involves 1) screening using Pap smears, which tests for precancerous cells on the surface of the cervix, or HPV DNA which tests for presence of the HPV virus in cervix cells; 2) If pap smear/HPV test are positive the woman is referred for a colposcopy guided biopsy and diagnosis where a contrast agent: Lugol’s Iodine or acetic acid is applied to the surface of the cervix and imaged with a colposcope. Suspicious areas are then biopsied for pathological assessment and diagnosis. Diagnosis can either be normal, low grade precancer, high grade pre-cancer or invasive cancer. 3) Based on diagnoses a treatment is referred. In most high resource sittings loop electrosurgical excision procedure (LEEP) or cryotherapy is performed to remove the lesion from the cervix. If the cancer has spread, either a hysterectomy, radiation or chemotherapy is performed depending on the stage of cancer. In lower resource settings however due to various reasons such as lack of infrastructure and loss of women to follow up, the WHO proposes a screen-and-treat approach which involves visual inspection with acetic acid or Lugol’s iodine and immediate treatment with cryotherapy (or LEEP if it is available) (WHO 2013).


Why do these disparities exist?

Cervical cancer mortality is low in most high-income countries due to high rates of early detection of cervical cancer and appropriate intervention. The introduction of Pap-smear based screening and HPV testing enabled cervical cancer screening coverage to be comprehensive. In the USA, since the introduction of Pap smears 40 years ago, the number of deaths per year due to cervical cancer has halved.

Access:

However, screening for cervical cancer remains a challenge in LMICs. Health infrastructure in many regions is not adequately equipped for services necessary for gynecological care. When samples need to be transported long distances for analysis, and when lab testing is often unreliable, cytology-based tests like the Pap smear are not able to provide timely and accurate diagnoses. The problem of poor health infrastructure is compounded by the issue of transport. The inadequate distribution of healthcare facilities results in women having to travel long distances to be screened and receive treatment; this naturally translates to a large time expense. Apart from the difficulty of the journey itself, the need to take time away from work and other responsibilities may deter some women from factor traveling to seek care at a clinic. As such, even if a woman demonstrates hallmarks of dysplasia and is made aware of her situation, she may not be able to attend a follow up visit for additional care. Furthermore, there may be possible cultural barriers to access. In some cultures, there may be fear or stigma associated with the screening process. As genital examinations are required for the cervical cancer screening, the screening exam can be seen as extremely personal or possibly even invasive.

Availability:

Although the country is making continued progress, there are significant human resource gaps within the medical sector. From 2014 figures, the physician deficit at Ministry of Health-run facilities exceeds 16,000 with gynecologists among one of the most needed of professionals (Oxford Business Group, 2016). As such, even if a woman makes it to a facility, she may not receive the care that she needs. Moreover, according to the National Superintendence of Health Insurance in Peru, 80% of the population had healthcare coverage as of December 2015. Although this is a significant jump from 63.5% in 2010, a significant number of people still lack coverage. Without healthcare coverage, people may be more reluctant to seeking care because of the associated healthcare costs (Oxford Business Group, 2016).

Awareness:

These effects are accentuated by lack of education and awareness of cervical cancer. In Peru, for example, many women in rural communities are not aware of cervical cancer and the need for regular screening, in spite of the high rates of incidence in the region (Paz-Soldan, 2012). For all these reasons, Pap-based screening has not succeeded in LMICs in the way it has transformed the scene of cervical cancer in high-income countries. Novel approaches to encourage early screening and detection of the disease are necessary to decrease the burden of cervical cancer in LMICs. Indeed, this was the premise for the WHO recommendation for a see-and-treat approach in these countries, as earlier mentioned.

How can we reduce these disparities?

One approach may be to adapt the current screening protocols for the specific needs of women in LMIC. While each country is unique and there are certainly regional differences within a country, at least in Peru the largest barriers for women to access cervical cancer screening include proximity of clinics and stigma or fear of pain during screening (Soldan 2013, Aguilar et al 2016). With most of the health services concentrated in Lima and other coastal areas, prevalence in rural, interior communities can be reduced by increasing the supply of diagnostic equipment and trained health professionals in those areas. However, if women fear pain or exposure and stigma during a pelvic exam, even the spread of current practices may not resolve the cervical cancer disparity. The development and implementation of a less invasive or self-administered diagnostic tool that reduces a woman’s discomfort or pain is key to reducing cervical cancer rates in Peru and similar LMICs.

References

1. Bosch, F. X., et al. "The causal relation between human papillomavirus and cervical cancer." Journal of clinical pathology 55.4 (2002): 244-265. MM wALBooMER, J. A. N., et al. "HUMAN PAPILLOMAVIRUS IS A NECESSARY CAUSE OF INVASIVE CERVICAL CANCER. VVORLDWIDE." J. pathol 189 (1999): 12-19. Muñoz, Nubia, et al. "Epidemiologic classification of human papillomavirus types associated with cervical cancer." New England Journal of Medicine348.6 (2003): 518-527. ARPH. "Making Sense of Cervical Cancer." Health Matters Fact Sheet. Association of Reproductive Health Professionals, n.d. Web. 22 Sept. 2016. <http://www.arhp.org/Publications-and-Resources/Patient-Resources/Fact-Sh.... World Health Organization. "WHO guidelines for screening and treatment of precancerous lesions for cervical cancer prevention: supplemental material: GRADE evidence-to-recommendation tables and evidence profiles for each recommendation." (2013). Vaccarella, Salvatore, et al. "Worldwide trends in cervical cancer incidence: impact of screening against changes in disease risk factors." European journal of cancer 49.15 (2013): 3262-3273.

Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55(2):74-108.

Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136(5):E359-86.

Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136(5):E359-86.

3.(ACCP) AfCCP. Cervical Cancer Prevention Fact Sheet, Recent Evidence on Cervical Cancer Screening in Low-Resource Settings Seattle, WA: ACCP; 2011 [Available from:http://screening.iarc.fr/doc/ACCP_cxca_screening_2011.pdf.

4. GLOBOCAN 2012: International Agency for Research on Cancer (IARC); 2012 [Available from: http://globocan.iarc.fr/old/burden.asp?selection_pop=224900&Text-p=World&selection_cancer=4162&Text-c=Cervix+uteri&pYear=18&type=1&window=1&submit=%C2%A0Execute Rising Coverage Improves Outlook for Peru Health Care: Oxford Business Group; 2016 [Available from: https://www.oxfordbusinessgroup.com/overview/clean-bill-health-coverage-... “Cervical Cancer." (2016): n. pag. American Cancer Society. Web. Accessed on 6 July 2016. Available from: http://www.cancer.org/cancer/cervicalcancer/detailedguide/cervical-cance... Paz-Soldán, Valerie A., et al. "Structural barriers to screening for and treatment of cervical cancer in Peru." Reproductive health matters 20.40 (2012): 49-58. Aguilar, Alfredo et al. “Control of Cervical Cancer in Peru: Current Barriers and Challenges for the Future.” Molecular and Clinical Oncology 5.2 (2016): 241–245. PMC. Web. 23 Sept. 2016.


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