Cervical cancer risk factors
This page presents risk factors for cervical cancer including, human papillomavirus (HPV), smoking, socioeconomic status and other factors. It is thought that 100% of cervical cancers are theoretically preventable, by preventing infection with HPV, which is present in all cervical cancers. Smoking also plays a part in causing some cervical cancer, increasing likelihood of infection with HPV or causing HPV infection to be more persistent. A study published in December 2011 estimated that around 7% of cervical cancers in the UK are caused by smoking.36
Members of the HPV family have been detected in cervical tumours worldwide with studies showing the presence of HPV in virtually all cervical tumours tested.1
The highest risks are associated with HPV types 16 and 18. Most HPV infections will not progress to cervical intraepithelial neoplasia (CIN) . 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 cancer.2,37
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
A study has shown that the main risk factors for CIN 3 among HPV positive women are early age at first intercourse, long duration of the most recent sexual relationship and cigarette smoking.4
For cigarette smoking there is 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).
Suggested co-factors for cervical cancer include age at first intercourse, number of life-time partners, co-infection with herpes simplex virus-2 or chlamydia trachomatis, parity, age at first birth, oral contraceptive use and family history.5,9,25-28 A lower risk has been shown in partners of men who have been circumcised.29 People diagnosed with genital warts (associated with infection with HPV 6 and HPV 11) have a 50% increased risk of cervical cancer, according to a large cohort study.44
Cervical cancer risk may be further increased in women with other sexually transmitted infections alongside HPV, a cohort study indicates.58
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section updated 04/04/14
HPV vaccination for schoolgirls aged 12 to 13 in the UK was introduced in September 2008. The programme uses the quadrivalent, Gardasil, vaccine, which prevents against types 6, 11, 16 and 18 (previously, the programme used Cervarix, which immunises against HPV types 16 and 18). The quadrivalent vaccine was shown in a phase III clinical trial to provide 98% protection against CIN and cervical cancer caused by HPV types 16 and 18, which are the strains of the virus most commonly associated with cervical cancer.32,33 HPV vaccination may also provide protection against CIN caused by other HPV types, and for women with evidence of previous infection with HPV 16 or 18 in blood samples.34,35
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section updated 10/01/13
Tobacco smoking is classified by IARC as a cause of cervical cancer.52 An estimated 7% of cervical cancers in the UK are linked to smoking.53 This association is independent of HPV infection, however smoking may inhibit immune response to HPV infection, and/or cause DNA damage in HPV-infected cells.54
Cervical cancer risk is twice as high in HPV-positive women who smoke, compared with those who do not smoke, pooled analyses and a large cohort study have shown.55-57 This increased risk may be restricted to squamous cell carcinomas.[ref 30] Risk of CIN3/CIS is twice as high in smokers compared with non-smokers, a large cohort study showed.57
Cervical cancer risk is lower in former smokers compared with current smokers, pooled analyses and a large cohort study have shown.55-57
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section updated 04/04/14
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 Scotland.13
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
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section updated 01/12/02
The International Agency for Research on Cancer (IARC) states that HIV is a cause of cervical cancer.43 Cervical cancer risk is sixfold higher in women with HIV/AIDS compared with the general population, a meta-analysis showed.22 Among women with HIV, cervical cancer risk may be reduced by treatment with highly active antiretroviral therapy (HAART), but evidence remains unclear.45-48
Cervical cancer risk is not increased in organ transplant recipients compared with the general population, US data have shown, perhaps due to effective cervical screening in this population.49,50 Though CIN3 risk was increased in transplant recipients in a Swedish cohort study, risk of invasive cervical cancer was increased only in kidney recipients.51 A meta-analysis showed organ transplant recipients have double the general population risk of cervical cancer.22
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section updated 28/02/14
As with smoking, the association between oral contraceptive (OC) use and cervical cancer is complicated by possible confounding with sexual behaviour.15 A meta-analysis found risk of invasive cervical cancer in current users of combined OCs increases by 7% for each year of use. The risk increase for five years of use is approximately 40%. The risk increase is temporary, and risk returns to the level of a never-user after 10 years of stopping use.17
A study published in December 2011 estimated that around 10% of cervical cancers in 2010 were linked to OCs. However, when the protective effect of OCs on ovarian and womb cancer were taken into account, OCs were estimated to have a net beneficial effect, reducing the number of cancers in women in the UK by almost 1,600.39
Other studies20, 21 have investigated the use of hormone replacement therapy and cervical cancer, but there are no clear conclusions.
A recent meta-analysis showed that women with HIV/AIDS have a six-fold increased risk of cervical cancer and women who have undergone organ transplant have more than double the risk, strongly suggesting that immunosuppression plays a role.22 The International Agency for Research on Cancer (IARC) states that HIV is a cause of cervical cancer.43
It has been estimated that around 1% of cervical cancers in women in the UK are linked to occupation.40,42 This estimate was based on exposure to tetrachloroethylene, which is classified by IARC as probably carcinogenic to humans.42,43 Exposure can take place in dry cleaning and metal degreasing.41
Diethylstilboestrol (DES) is a drug that was given to some women in the 1940s-60s to prevent miscarriage. IARC states that exposure to DES in the womb is a cause of cervical cancer.43
Risk of cervical cancer is almost twice as high in women whose sister or mother has been diagnosed with the disease, but cervical cancer is not hereditary. Rather, close relatives may have similar lifestyles which influence their risk of cervical cancer (for example sexual behaviour or smoking), and/or they may have shared genetic factors (for example affecting immune response to HPV infection).31
section reviewed 01/12/02
section updated 01/12/02
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- Walboomers JMM, Meijer C. Do HPV-negative cervical carcinomas exist?[editorial]. Journal Pathology 1997; 181:253-254.
- Bosch FX, Lorincz A, Muñoz N, et al. The causal relation between human papillomavirus and cervical cancer . Journal of clinical pathology 2002; 55(4):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 JM, Evans CD, Yule R, 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. Br J Cancer 2000; 83:1565-1572.
- Schottenfeld D, 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 SF, Vassallo J, Pinto GA, et al. Langerhans' cells in cervical condyloma and intraepithelial neoplasia in smoking and non-smoking adolescents. Acta Derm Venereol 1996; 76(6):493-494.
- Poppe WA, Drijkoningen M, Ide PS, 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.
- Berrington de González A, Sweetland S, Green J, et al. Comparison of risk factors for squamous cell and adenocarcinomas of the cervix: a meta-analysis. Br J Cancer 2004; 90(9):1787-91.
- Szarewski A, Jarvis MJ, Sasieni P. Effect of smoking cessation on cervical lesion size. Lancet 1996; 347:941-943.
- Acladious NN, Sutton C, Mandal D, 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):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, Harding S, Bethune A. Incidence of Health of the nation cancers by social class. Population Trends, 1997.
- Zondervan KT, Carpenter LM, Painter R. Oral Contraceptives and Cervical Cancer- Further findings from the Oxford Family Planning Association contraceptive study. British Journal of Cancer 1996; 73:1291-1297.
- Beral V, Hermon C, Kay C. 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; 318:96-100.
- Appleby P, Beral V, Berrington de González A, et al. Cervical cancer and hormonal contraceptives: collaborative reanalysis of individual data for 16,573 women with cervical cancer and 35,509 women without cervical cancer from 24 epidemiological studies. Lancet 2007; 370(9599):1609-21.
- Hildesheim A, Herrero R, Castle PE, et al. HPV co-factors related to the development of cervical cancer: results from a population-based study in Costa Rica. Br J Cancer 2001; 84(9):1219-1226.
- Muñoz N, Franceschi S, Bosetti C, et al. Role of parity and human papillomavirus in cervical cancer: the IARC multicentric case-control study. Lancet 2002; 359:1093-1101.
- Parazzini F, La Vecchia C, Negri E, et al. Case-control study of ostrogen replacement therapy and risk of cervical cancer. British Medical Journal 1997; 315:85-88.
- Lacey JV Jr, Brinton LA, Barnes WA, et al. Use of hormone replacement therapy and adenocarcinomas and squamous cell carcinomas of the uterine cervix. Gynecologic Oncology 2000; 77:149-154.
- Grulich AE, van Leeuwen MT, Falster MO, et al. Incidence of cancers in people with HIV/AIDS compared with immunosuppressed transplant recipients: a meta-analysis. Lancet 2007; 370(9581):59-67.
- Gallagher B, Wang Z, Schymura MJ, et al. Cancer incidence in New York State acquired immunodeficiency syndrome patients. American Journal of Epidemiology 2001; 154(6):544-556.
- Dal Maso L, Serraino D, Franceschi S. Epidemiology of AIDS-related tumours in developed and developing countries. European Journal of Cancer, 2001. 37(10): p. 1188-1201.
- Smith, J.S., et al., Herpes Simplex Virus-2 as a Human Papillomavirus Cofactor in the Etiology of Invasive Cervical Cancer. JNCI 2002; 94(21)1604-1625.
- Smith JS, Herrero R, Bosetti C, et al. Chlamydia trachomatis and invasive cervical cancer: a pooled analysis of the IARC multicentric case-control study. Int J Cancer 2004; 111(3):431-9.
- Smith JS, Bosetti C, Muñoz N, et al. Risk of cervical cancer associated with Chlamydia trachomatis antibodies by histology, HPV type and HPV cofactors. Int J Cancer 2007; 120(3):650-5.
- Hemminki K, Chen B. Familial risks for cervical tumors in full and half siblings: etiologic apportioning. Cancer Epidemiol Biomarkers Prev 2006; 15(7):1413-4.
- Castellsagué X, Bosch FX, Muñoz N, et al. Male circumcision, penile human papillomavirus infection, and cervical cancer in female partners. N Engl J Med 2002; 346(15):1105-1112.
- International Collaboration of Epidemiological Studies of Cervical Cancer. Comparison of risk factors for invasive squamous cell carcinoma and adenocarcinoma of the cervix: collaborative reanalysis of individual data on 8,097 women with squamous cell carcinoma and 1,374 women with adenocarcinoma from 12 epidemiological studies. Int J Cancer 2007; 120(4):885-91.
- Hussain SK, Sundquist J, Hemminki K. Familial clustering of cancer at human papillomavirus-associated sites according to the Swedish Family-Cancer Database. Int J Cancer 2008; 122(8):1873-8.
- Clifford GM, Smith JS, Plummer M, et al. Human papillomavirus types in invasive cervical cancer worldwide: a meta-analysis. Br J Cancer 2003; 88(1):63-73.
- FUTURE II Study Group. Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions. N Engl J Med 2007;356:1915-27.
- Paavonen J, Naud P, Salmeron J, et al. Efficacy of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by oncogenic HPV types (PATRICIA): final analysis of a double-blind, randomised study in young women. Lancet 2009; 374(9686):301-14.
- Szarewski A, Poppe W, Skinner S, et al. Efficacy of the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine in women aged 15-25 years with and without serological evidence of previous exposure to HPV-16/18. Int J Cancer 2012; 131(1):106-16.
- Parkin DM, Boyd L, Walker LC. The fraction of cancer attributable to lifestyle and environmental factors in the UK in 2010. Summary and conclusions. Br J Cancer 6 Dec 2011; 105 (S2):S77-S81.
- Parkin DM. Cancers attributable to infection in the UK in 2010. Br J Cancer 2011; 105(S2):S49-S56.
- Parkin DM. Tobacco-attributable cancer burden in the UK in 2010. Br J Cancer 2011; 105(S2):S6-S13.
- Parkin DM. Cancers attributable to exposure to hormones in the UK in 2010. Br J Cancer 2011; 105(S2):S42-S48.
- Parkin, DM. Cancers attributable to occupational exposures in the UK in 2010. Br J Cancer 2011; 105(S2):S70-S72.
- Siemiatycki J, Richardson L, Straif K, et al. Listing occupational carcinogens. Environ Health Perspect 2004; 112(15):1447-59.
- Rushton L, Bagga S, Bevan R, et al. Occupation and cancer in Britain. Br J Cancer 2010; 102:1428-1437.
- Cogliano VJ, Baan R, Straif K, et al. Preventable exposures associated with human cancers. JNCI 2011; 103:1827-39.
- Blomberg M, Friis S, Munk C, et al. Genital warts and risk of cancer: a Danish study of nearly 50 000 patients with genital warts. J Infect Dis 2012; 205(10):1544-53.
- Adler DH. The impact of HAART on HPV-related cervical disease. Curr HIV Res. 2010 Oct;8(7):493-7.
- Chen YC, Li CY, Liu HY, et al. Effect of antiretroviral therapy on the incidence of cervical neoplasia among HIV-infected women: a population-based cohort study in Taiwan. AIDS. 2013 Dec 10.
- Blitz S, Baxter J, Raboud J, et al. Evaluation of HIV and highly active antiretroviral therapy on the natural history of human papillomavirus infection and cervical cytopathologic findings in HIV-positive and high-risk HIV-negative women. J Infect Dis. 2013 Aug 1;208(3):454-62.
- Adler DH, Kakinami L, Modisenyane T, et al. Increased regression and decreased incidence of human papillomavirus-related cervical lesions among HIV-infected women on HAART. AIDS. 2012 Aug 24;26(13):1645-52.
- Madeleine MM, Finch JL, Lynch CF, et al. HPV-related cancers after solid organ transplantation in the United States. Am J Transplant. 2013 Dec;13(12):3202-9.
- Engels EA1, Pfeiffer RM, Fraumeni JF Jr, et al. Spectrum of cancer risk among US solid organ transplant recipients. JAMA. 2011 Nov 2;306(17):1891-901.
- Krynitz B1, Edgren G, Lindelöf B, et al. Risk of skin cancer and other malignancies in kidney, liver, heart and lung transplant recipients 1970 to 2008--a Swedish population-based study. Int J Cancer. 2013 Mar 15;132(6):1429-38.
- International Agency for Research on Cancer. List of Classifications by cancer sites with sufficient or limited evidence in humans, Volumes 1 to 105*. Available from: http://monographs.iarc.fr/ENG/Classification/index.php. Accessed October 2013.
- Parkin DM, Boyd L, Walker LC. The fraction of cancer attributable to lifestyle and environmental factors in the UK in 2010. Br J Cancer. 2011 Dec 6;105 Suppl 2:S77-81.
- Castle E. How Does Tobacco Smoke Contribute to Cervical Carcinogenesis? . J Virol. Jun 2008; 82(12): 6084–6086.
- Plummer M, Herrero R, Franceschi S, et al. Smoking and cervical cancer: pooled analysis of the IARC multi-centric case--control study. Cancer Causes Control. 2003 Nov;14(9):805-14.
- Vaccarella S, Herrero R, Snijders PJ, et al. Smoking and human papillomavirus infection: pooled analysis of the International Agency for Research on Cancer HPV Prevalence Surveys. Int J Epidemiol. 2008 Jun;37(3):536-46.
- Roura E, Castellsagué X, Pawlita M, et al. Smoking as a major risk factor for cervical cancer and pre-cancer: Results from the EPIC cohort. Int J Cancer. 2013 Dec 13.
- Castellsagué X, Pawlita M, Roura E, et al. Prospective seroepidemiologic study on the role of Human Papillomavirus and other infections in cervical carcinogenesis: Evidence from the EPIC cohort . Int. J. Cancer. doi: 10.1002/ijc.28665.