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Biology and Genetics - Cervical Cancer Screening

Background

Cervical cancer is a tumour which comes from the cervix uteri, the narrow lower end of the uterus that connects the uterus to the vagina. Cancer of the cervix starts as a small area of abnormal cells (a precancerous lesion called dysplasia). Over time, these cells can become more abnormal, producing a localized form of cancer called carcinoma in situ. If this is untreated, it can develop into a full malignant cancer. Treatment of dysplasia or carcinoma in situ can be curative. Cervical cancer usually occurs as the result of long-standing infection with certain types of a virus: human papillomavirus (HPV). Most HPV infections will resolve spontaneously in healthy individuals.  However, in some cases, infection can become persistent and can lead normal cervical cells to gradually change into cervical precancerous lesions.


Health Risks

Cervical cancer is the second most common type of cancer of the reproductive system in women (after breast cancer). Worldwide, it kills more than 288,000 women each year. At least 80 percent of cervical cancer deaths occur in developing countries. Rates are highest in the developing countries: South-East Asia, sub-Saharan Africa, and parts of Latin America. The main reason for the high mortality in developing countries is the lack of organized and effective screening programs which can detect and treat pre-cancerous lesions.

In Canada, cervical cancer is a moderately common cancer (the 11th leading cancer in women), accounting for about 1,350 new cases and 350 deaths per year. The incidence of cervical cancer has dropped by about 55% since 1973. Mortality has dropped even more: by 62%.  These changes are mainly due to the use of Pap smears and early treatment.  Similar trends have been noted in the USA.

Cervical cancer tends to occur in midlife. Most women diagnosed with cervical cancer are between 45 and 55 years old.  In general, women are diagnosed with cervical cancer at a younger age than for most other cancers. All women except for those who had a total hysterectomy are at risk of developing cervical cancer.

The main risk factor for cervical cancer is an infection with a high-risk type of Human Papillomavirus (HPV), types 16 and 18 in particular. HPV infection is a sexual transmitted virus. It is estimated that at least 50% of sexually active women will be infected with one or more types of HPV during their lifetime. Most of these infections will be spontaneously cured with no long term health effects. However, persistent infection can lead to cervical cancer. The risk of becoming infected with a persistent form of HPV can be affected by certain behaviours and life experiences:

  • Sexual behaviours including;
    • lifetime number of partners;
    • early age at first sexual intercourse;
    • the likelihood that at least one sexual partner was an HPV carrier
  • High parity, especially with five or more full-term pregnancies;
  • Co-infection with other sexually transmitted infections (e.g. HIV, Chlamydia trachomatis or herpes simplex virus-2) can facilitate HPV infection;
  • A weakened immune system;
  • Smokers are twice as likely as non-smokers to develop cervical cancer.

Cervical cancer most often has no discernable symptoms, especially during the early stages. If not detected with screening procedures, the cancerous tumour can grow and invade adjacent organs in the pelvic area, such as the bladder or the rectum. It may also invade and obstruct the ureters from the kidneys. This can block the flow of urine from the kidneys and cause ‘bloating’ of the kidneys (hydronephrosis) and eventually lead to kidney failure. Advanced cervical cancer may spread through the regional lymphatic system or blood vessels, resulting in widespread metastasis to lungs, liver, bones, or other parts of the body.

The survival rate from cervical cancer is strongly influenced by the stage at which diagnosis was made. Lesions detected at a ‘in-situ’ stage are curable (100% survival).  The five-year survival rate for the earliest stage of cervical cancer is about 90 percent.  However, the five-year survival is much worse if the cancer has spread to distant parts of the body (around 5%). The primary treatment of cervical cancer uses either surgery or radiotherapy. Chemotherapy isn’t an effective way to treat this cancer. Complications from cervical cancer or side effects from its treatments can lead to kidney failure, bowel or urinary incontinence, heavy vaginal bleeding, or infertility.


Risk Management

Cervical cancer is one of the most preventable cancers, even in women at high risk for the cancer.  Regular screening can enable early detection of precancerous changes (dysplasia) in the cervical tissue. These lesions, when successfully treated or removed, will not develop into invasive cervical cancer. The marked drop in the frequency and deaths from cervical cancer over the past 30 years shows how effective screening can be.

The primary screening procedure for cervical cancer is the Pap smear. It was first introduced to Canada in 1949 in British Columbia.  Pap testing is offered as an insured medical service in all Canadian provinces. Provincial cervical screening programs recommend that all sexually active women should be screened annually until they have had 3 successive normal Pap tests. Then, they should continue to be screened every 2-3 years until they reach age 70. Pap test results which show abnormalities lead to further medical testing and treatment. This can include additional pap testing with close monitoring or colposcopy (a procedure which uses a fiber optic device to let your doctor see the cervix and vagina). Physicians also can use other screening procedures (e.g. liquid-base cytology or HPV DNA analysis of cervical cells). However, these approaches are not yet used for general screening. In Europe, the European Guidelines on Quality Assurance for Cervical Cancer Screening provides guidance detection and management of precursors lesions of the cervix. While in Canada and the United States, the provincial or state cervical screening programs are responsible for setting such guidelines and recommendations.

In 2003, Health Canada reported that nearly 80% of eligible women had had a pap smear in the previous three years. In an effort to further increase the use of pap smears, organized campaigns have been developed in Canada to increase public awareness of cervical cancer health risks and educate women about details of available screening programs.  Provinces are exploring the development of ‘call-back’ systems under which women would receive a mailed reminder when they are due for their next pap smear.

The application of pap testing in developing countries is less comprehensive than in developed countries. This is one reason why cervical cancer incidence and mortality in these countries remain high. The low use of pap smears reflects competing health priorities and economic factors, as well as issues in training medical staff in the appropriate interpretation of the tissue samples obtained by the smear. Alternatives to pap testing are being evaluated for use in developing countries, including: visual inspection of the cervix combined with treatment with 4% acetic acid and infra-red examination of pap smears. The impact of these approaches is currently unclear.
 
A new HPV vaccine against the high-risk (oncogenic) virus types was introduced in 2006 in a number of countries. In Canada, the Province of Ontario began offering in 2007 HPV vaccination to grade 8 girls under a voluntary programme. Several randomized control trials have shown the vaccine to be almost 100% effective in preventing disease caused by the HPV types covered by the vaccine in HPV naïve women. However, this new vaccine’s real-world effectiveness, long term safety, and length of immunologic protection remain uncertain and require further study. The vaccine might be especially promising for underserved regions in developed countries and developing countries lacking an effective cervical screening program. However, in developed countries with successful cervical cancer screening programs like Canada and the United States, the death rate from cervical cancer has been declining for over 30 years. The utility of the HPV vaccine to accelerate this decline is unclear.  However, if the vaccine is proven to be appropriate for wide scale application, the need for frequent pap testing might be eliminated as current teenagers enter adult life. Pap testing would still need to be continued for the women who are already HPV-infected.


Useful Links

Alliance for Cervical Cancer Prevention
http://www.alliance-cxca.org/

Canadian Cancer Society
http://www.cancer.ca

Cancer Care Ontario
http://www.cancercare.on.ca/index_cervicalScreening.htm

Public Health Agency of Canada - Cervical Cancer Screening in Canada: 1998 Surveillance Report
http://www.phac-aspc.gc.ca/publicat/ccsic-dccuac/index-eng.php
http://www.phac-aspc.gc.ca/std-mts/hpv-vph/hpv-vph-vaccine_e.html 

Cervical Cancer Prevention and Control Network (CCPCN)
http://www.ccpcn.ca/en/home.php

International Agency for Research on Cancer
http://screening.iarc.fr/cervicalindex.php?lang=1

International Federation of Gynecology and Obstetrics
www.figo.org

National Cancer Institute (NCI) ‘What you need to know about cervical cancer’
http://www.cancer.gov/cancertopics/wyntk/cervix
http://www.cancer.gov/cancertopics/types/cervical/

National Cervical Cancer Coalition (NCCC)
http://www.nccc-online.org/

Further reading

Canadian Cancer Strategy (2006).  Canadian Cancer Strategy: A Cancer Plan for Canada, Discussion Paper. http://www.cancer.ca/ccs/internet/standard/0,3182,3172_335265__langId-en,00.html. Accessed, June 12th, 2007.

Cancer Care Ontario.  News and information on Cervical Cancer. Toronto: Insight on Cancer, Canadian Cancer Society, 1-32, 2005.

Ferlay, J., Bray, F., Pisani, P., Parkin, D.M. J.GLOBOCAN 2002: Cancer incidence, mortality and prevalence worldwide, IARC CancerBase No. 5. version 2.0. Lyon, France: IARC Press, 2004.

International Agency for Research on Cancer Working Group.  IARC handbooks of cancer prevention: cervix cancer screening.  Vol 10. Lyon: IARC Press, 2005.

IARC Screening Group (2007). Cervical Cancer. http://screening.iarc.fr/cervicalindex.php?lang=1 Accessed June 12th, 2007. 

National Cancer Institute of Canada.  Canadian Cancer Statistics 2005.  Toronto, Canada, 2005.

Parkin, D.M., Whelan, S.L.; Ferlay, J., Teppo, L., Thomas, D.B. (eds). Cancer incidence in five continents.  Volume VIII. Lyon, FR: International Agency for Research on Cancer, 2002.

Contributors: Sara Torres, Fan Mo

Last reviewed: June 2nd, 2010



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