Cancer Research UK : Cervical Cancer Risk Factors

Cervical Cancer Risk Factors

This page presents risk factors for cervical cancer including, human papillomavirus, smoking, socioeconomic status and other factors.

Human papillomavirus (HPV) and cervical cancer risk

Members of the HPV family have been detected in cervical tumours worldwide with studies showing the presence of HPV in virtually all cervical tumours tested1.

The highest risks are associated with HPV types 16 and 18. Most HPV infections will not progress to Cervical Intraepithelial Neoplasia . However, it is believed that cervical cancer will not develop without the presence of persistent HPV DNA and it has been proposed as the first ever identified “necessary cause” of a human cancer2.

Genital HPV is generally sexually transmitted through contact with infected cervical, vaginal, vulvar, penile or anal epithelium. Genital HPV infection may involve areas that are not easily covered by a condom so correct condom use may not protect against infection.

An analysis of studies on the prevalence of HPV infection in the population led to the conclusions that HPV is more common in younger women than older women, that HPV is rarely detected in women with no previous sexual activity and that there are no apparent geographical differences in HPV prevalence.

The percentage of the study populations who were HPV positive varied from 0% to 48% depending on the group studied. Results also show that HPV 16 infection is more common than any other classified type of HPV 3. Risk factors for HPV infection include number of sexual partners, a relatively recent new sexual relationship and a history of previous miscarriage 4.

The Deacon[4] study found that the main risk factors for CIN 3 among HPV positive women were early age at first intercourse, long duration of the most recent sexual relationship and cigarette smoking.

For cigarette smoking there was a strong dose-response relationship. The risk of CIN 3 for women who were HPV positive and smoking 20 or more cigarettes a day was two and a half times that of women who had never smoked. The authors concluded that even though smoking was not a risk factor for HPV, smoking acted with HPV to cause cervical neoplasia (see also Smoking section below).

Other suggested co-factors include age at first intercourse, co-infection with other sexually transmitted infections, parity, oral contraceptive use and genetics 5.

Smoking and cervical cancer risk

The causal role of smoking in cervical cancer is difficult to establish because of possible confounding with sexual behaviour. Cigarette smoking has been linked to inactivation in cervical tumours of the fragile histidine triad 6 putative tumour suppressor gene (which is also altered in most tobacco-associated lung cancers).

Smoking may also be associated with a decrease in the number of Langerhans’ immune cells in the cervix epithelium, suggesting a decrease in epithelial cell-mediated immune responses in smokers 7,8.

One study found a positive association between smoking and cervical squamous cell carcinoma but an inverse association between smoking and cervical adenocarcinoma, indicating that the histologic sub types may be affected differently by smoking9.

Reduction in early cervical lesion size in women who gave up smoking after diagnosis has been reported10. Also smokers have been found to have a 3 fold increased risk of treatment failure of CIN compared to non-smokers and therefore require more intensive follow-up after treatment11.

Socio-economic status and cervical cancer risk

In England and Wales 12, incidence and mortality from cervical cancer has been analysed by to Carstairs deprivation category (Figure 4.1).

Figure 4.1: European age-standardised incidence of and mortality,cervical cancer by deprivation category, England and Wales, 1990-93

Download this chart (27KB)

Women living in the most deprived areas have rates more than three times as high as those in the least deprived areas. A strong positive association between cervical cancer and deprivation has also been described for incidence data from Scotland13.

In addition a link has been demonstrated between social class and cervical cancer. Data from a longitudinal study, representing 1% of the England and Wales population, indicates that cervical cancer incidence is considerably higher among women of working age in manual than in non-manual classes 14.

Other cervical cancer risk factors

As with smoking, the association between oral contraceptive use and cervical cancer is complicated by possible confounding with sexual behaviour15. A follow up study16 of mortality associated with oral contraceptive use found a relative risk of death from cervical cancer of 2.5 (CI 1.1-6.1) among current and recent users (within previous 10 years) compared to never users.

A three-fold increased risk for invasive squamous-cell cervical cancer was found for women who were HPV positive and had used oral contraception for five or more years17. Another study found that oral contraceptive use may only be associated with cervical cancer in some subgroups of women18.

High parity has been linked to increased risk of squamous-cell carcinoma of the cervix among HPV positive women. The reduction in cervical cancer seen in many countries could therefore be partly explained by the general decline in parity19. Other studies20,21 have investigated the use of hormone replacement therapy and cervical cancer, but there are no clear conclusions.

Studies have also shown that among HIV positive women there is an increased risk of invasive cervical cancer 22-24. As both infection with HPV and HIV is linked with sexual transmission it is possible that the relationship could be either through the frequent occurrence of HPV among HIV infected women and / or the effect of HIV on the immune system thus promoting persistent HPV infection.

References for cervical cancer risk factors

Walboomers, J.M.M. and C. Meijer, Do HPV-negative cervical carcinomas exist?[editorial]. Journal Pathology, 1997. 181: p. 253-254.
Bosch, F.X., et al., The causal relation between human papillomavirus and cervical cancer. Journal of clinical pathology, 2002. 55(4): p. 244-265.

International Agency for Research on Cancer, IARC Monographs on the evaluation of carcinogenic risks to humans: human papillomaviruses. Vol. 64. 1995, Lyon: World Health Organisation.
Deacon, J., et al.,Sexual behaviour and smoking as determinants of cervical HPV infection and of CIN 3 among those infected. A case-control study nested within the Manchester cohort. British Journal of Cancer, 2000. 83: p. 1565-1572.
Schottenfeld, D. and J. Fraumeni, eds. Cancer epidemiology and prevention. 2nd ed. 1996, Oxford University Press: Oxford.
Holschneider, C., et al. Lost fragile histidine triad (FHIT) gene expression may link cigarette smoking and cervical cancer [abstract]. in Program and Abstracts of the Society for Gynecologic Oncologists 31st Annual Meeting; February 5-9. 2000. San Diego, California.
Derchain, S., et al., Langerhans' cells in cervical condyloma and intraepithelial neoplasia in smoking and non-smoking adolescents. Acta Derm Venereol, 1996. 76(6): p. 493-494.
Poppe, W., et al.,Langerhans' cells and L1 antigen expression in normal and abnormal squamous epithelium of the cervical transformation zone. Gynecol Obstet Invest, 1996. 41(3): p. 207-213.
Lacey, J.J., et al., Associations between smoking and adenocarcinomas and squamous cell carcinomas of the uterine cervix (United States). Cancer Causes Control, 2001. 12(2): p. 153-161.
Szarewski, A., M.J. Jarvis, and P. Sasieni,Effect of smoking cessation on cervical lesion size. Lancet, 1996. 347: p. 941-943.
Acladious, N., et al., Persistent human papillomavirus infection and smoking increase risk of failure of treatment of cervical intraepithelial neoplasia (CIN). International Journal of Cancer, 2002. 98(3): p. 435-439.
Quinn, M., et al., Cancer Trends in England & Wales 1950-1999. Vol. SMPS No. 66. 2001: TSO.
Harris, V., et al.,Cancer Registration Statistics: Scotland 1986-1995. 1998, Edinburgh: ISD Scotland Publications.
Brown, J., S. Harding, and A. Bethune,Incidence of Health of the nation cancers by social class. Population Trends, 1997.
Zondervan, K., et al.,Oral Contraceptives and Cervical Cancer- Further findings from the Oxford Family Planning Association contraceptive study. British Journal of Cancer, 1996. 73: p. 1291-1297.
Beral, V., C. Hermon, and C. Kay,Mortality associated with oral contraceptive use: 25 year follow up of cohort of 46 000 women from Royal College of General practitioners' oral contraception study. British Medical Journal, 1999. 318: p. 96-100.
Moreno, V., et al., Effect of oral contraceptives on risk of cervical cancer in women with human papillomavirus infection: the IARC multicentric case-control study. Lancet, 2002. 359: p. 1085-1092.
Hildesheim, A., et al.,HPV co-factors related to the development of cervical cancer: results from a population-based study in Costa Rica. British Journal of Cancer, 2001. 84(9): p. 1219-1226.
Munoz, N., et al., Role of parity and human papillomavirus in cervical cancer: the IARC multicentric case-control study. Lancet, 2002. 359: p. 1093-1101.
Parazzini, F., et al., Case-control study of ostrogen replacement therapy and risk of cervical cancer. British Medical Journal, 1997. 315: p. 85-88.
Lacey, J.J., et al., Use of hormone replacement therapy and adenocarcinomas and squamous cell carcinomas of the uterine cervix. Gynecologic Oncology, 2000. 77: p. 149-154.
Serraino, D., et al.,Risk of invasive cervical cancer among women with, or at risk for, HIV infection.International Journal of Cancer, 1999. 82(3): p. 334-337.
Gallagher, B., et al.,Cancer incidence in New York State acquired immunodeficiency syndrome patients.American Journal of Epidemiology, 2001. 154(6): p. 544-556.
Dal Maso, L., D. Serraino, and S. Franceschi, Epidemiology of AIDS-related tumours in developed and developing countries. European Journal of Cancer, 2001. 37(10): p. 1188-1201.