Awareness

Understanding Cervical Cancer

FAST FACTS
•    Worldwide, cervical cancer kills one woman every two minutes
•    Cervical cancer is caused by certain types of a virus called human papillomavirus (HPV)
•    HPV types 16 and 18 are the most common cancer-causing virus types and account for over 70 percent of all cervical cancer cases globally
•    Globally HPV types 45, 31 and 33 are among the next most common cancer-causing types
•    Up to 80 percent of women will acquire an HPV infection in their lifetime and almost 50 percent of these infections will be with a cancer-causing virus type
•    Women remain vulnerable to HPV infection throughout their sexually active life
•    The most effective means of tackling cervical cancer is through prevention. It is now possible to vaccinate against most common cancer-causing strains of HPV
•    As well as vaccination, cervical cancer screening remains a valuable intervention for all sexually active women

The global burden of cervical cancer
Worldwide, cervical cancer:
•    Kills one woman every two minutes1
•    Is the second biggest cause of female cancer mortality2A

In South Africa, cervical cancer:
•    Is the most common cancer in women1
•    Will affect more than 6700 new women every year1
•    Will kill almost 3700 women every year1

In women who do not undergo regular screening, cervical cancer can be a silent killer, taking several years to develop.3A By the time symptoms appear, the disease is often at an advanced stage.3B As well as the high death toll associated with cervical cancer, women who survive may be left infertile by radical surgery needed to remove the cancerous tissue.

HPV: the virus behind cervical cancer
Cervical cancer is predominantly caused by a virus called human papillomavirus (HPV) which is transmitted through sexual activity.4  Condoms do not fully protect women from HPV infection since the spread of the virus does not depend on full intercourse but may occur simply through skin-to-skin contact in the genital area.5,6
•    There are about 100 known types of HPV7 of which 15 can cause cervical cancer8
•    HPV types 16 and 18 are the most common cancer-causing virus types and account for over 70 percent of all cervical cancer cases worldwide9A

HPV 16, 18 and 45 are particularly concerning since these three are associated with approximately 90% of cases of adenocarcinoma.9C Adenocarcinoma is a particularly dangerous and aggressive form of cervical cancer which is harder to detect through routine screening and is more likely to lead to relapse and death.  The incidence of adenocarcinoma is increasing, particularly in young women.

It is estimated up to 80 percent of women will acquire an HPV infection in their lifetime and almost 50 percent of these will be with a cancer-causing virus type.10,11,12 Most infections are cleared spontaneously but, when they persist, the risk of developing cervical cancer rises.13A  A persistent infection with a cancer-causing virus type may result in the development of abnormal and pre-cancerous cervical cell changes which over time can develop into cancer.13B

HPV is a particularly challenging virus as it is able to evade detection by the immune system.  As a purely mucosal virus which does not enter the bloodstream and does not kill the cells it infects, HPV avoids sending out the usual signals that trigger the immune system.14A Thus, the natural immune response, following infection may not be strong enough to protect against initial or subsequent infection.14B,15,16

Figure 2: Development of cervical cancer

The importance of screening
Regular screening using smear testing provides an early warning system, detecting evidence of abnormal or pre-cancerous cells. Although receiving an abnormal smear test result can be a traumatic experience, as can the surgical procedures used to eliminate the affected cells, cervical cancer screening remains a valuable intervention for all women.

The potential of vaccination
The most effective means of tackling cervical cancer is prevention; and vaccination against cancer-causing HPV types 16 and 18 is now available. It has been estimated that alongside regular screening, this could reduce the risk of developing cervical cancer by 94 percent, compared to no intervention.17

Men can carry and transmit HPV and therefore may contribute to the risk of cervical cancer in their female partner. However, research has shown that universal mass vaccination of males will only provide a minimal incremental reduction in cervical cancer cases if coverage in females is high, and at a considerably higher cost.18 The exact level of female coverage to justify the cost efficacy of male vaccination has not yet been determined. Therefore reducing the HPV disease burden in women should be achieved better and faster if a large proportion of women are vaccinated.19-23

References

1.    Ferlay J, Bray F, Pisani P, Parkin DM. GLOBOCAN 2002: Cancer incidence, mortality and prevalence worldwide. IARC CancerBase No.5, version 2.0 IARC Press, Lyon, 2004. Available at: http://www-dep.iarc.fr
2.    World Health Organization. Initiative for Vaccine Research.  http://www.who.int/vaccine_research/diseases/hpv/en/  Accessed on April 20, 2009.
3.    Canavan TP, Doshi NR. Cervical cancer. Am Fam Physician March 2000; 61(5): 1369-76.
4.    Baseman JG, Koutsky LA. The epidemiology of human papillomavirus infections J Clin Virol 2005; 32 Suppl 1; S16-24
5.    Schiffman M, Kjaer SK. Natural history of anogenital human papillomavirus infection and neoplasia. J Natl Cancer Inst Monogr 2003; 31: 14-19
6.    Winer RL, Hughes JP, Feng Q et al. Condom use and the risk of genital human papillomavirus infection in young women. N Engl J Med 2006 June 22; 354(25):2645-54.
7.    WHO. Expert Committee on Biological Standardization. Guidelines to assure the quality, safety and efficacy of recombinant Human Papillomavirus virus-like particle vaccines, accessed on 27/3/2009 at http://screening.iarc.fr/doc/WHO_vaccine_guidelines_2006.pdf
8.    Muñoz N, Bosch FX, de Sanjose S, et al. Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med 2003; 348: 518-527
9.    Bosch X, Burchell A, Schiffmann M et al. Epidemiology and Natural History of Human Papillomavirus Infections and Type-Specific Implications in Cervical Neoplasia. Vaccine 26S (2008) K1–K16
10.    Bosch FX, de Sanjose S. Chapter 1 : Human papillomavirus and cervical cancer – burden and assessment of causality. J Natl Cancer Inst Monogr, 2003; 3-13
11.    Brown DR, Shew ML, Qadadri B, Neptune N, Vargas M, Tu W, Juliar BE, Breen TE, Fortenberry JD. A longitudinal study of genital human papillomavirus infection in a cohort of closely followed adolescent women. J Infect Dis 2005; 191: 182-192
12.    Gravitt PE, Jamshidi R. Diagnosis and management of oncogenic cervical human papillomavirus
infection. Infect Dis Clin North Am. 2005;19:439-458
13.    Kiviat NB, Koutsky LA. Specific human papillomavirus types as the causal agents of most cervical intraepithelial neoplasia: implications for current views and treatment. Journal of the National Cancer Institute 1993; 85(12): 934-5.
14.    Stanley M. Immune responses to human papillomavirus. Vaccine 2006, Vol 24S1/16-22
15.    Viscidi et al.  Seroactivity to human papillomavirus (HPV) typwes 16,18 or 31 and risk of subsequent HPV infection: results from a population-based study in Costa Rica.  Cancer Epidemiology Biomarkers and Prevention 2004; 13: 324-327
16.    Mayrand M, Coutlée F, Hankins C, Lapointe N, Forest P, De Ladurantaye M, et al.  Detection of Human Papillomavirus Type 16 DNA in Consecutive Genital Samples Does Not Always Represent Persistent Infection as Determined by Molecular Variant Analysis. J Clin Microbiol September 2000: 3388–3393
17.    Goldie SJ, Kohli M, Grima D, Weinstein MC, Wright TC, Bosch FX, Franco E. Projected clinical benefits and cost-effectiveness of a human papillomavirus 16/18 vaccine. J Natl Cancer Inst 2004b; 96: 604-615. 13.
18.    Kim JJ, Folse H, Murray M et al. Should Men Be Included in a Vaccination Program Against HPV Infection in a Resource-Constrained Setting?  Oral presentation PS 10-3, 23rd International Papillomavirus Conference and Clinical Workshop; September 1-7, 2006. Prague, Czech Republic.
19.    Taira AV et al. Evaluating human papillomavirus vaccination programs. Emerg. Infect. Dis. 2004;10(11):1915-1923
20.    Leon R. Ladies first: should boys be vaccinated against HPV? Can Fam Physician 2008. July;54(7):967-968.
21.    Regan DR et al. Should we be vaccinating boys as well as girls with the HPV vaccine? Australian Sexual Health Conference 15-17 September 2008
22.    Hughes JP et al. The theoretical population-level impact of a prophylactic human papillomavirus vaccine. Epidemiology 2002;13(6):631-639
23.    Goldie. J et al. A Comprehensive Natural History Model of HPV infection and Cervical Cancer to estimate the clinical impact of a prophylactic HPV-16/18 vaccine. Int. J. Cancer: 106, 896–904 (2003)