Oral contraceptives and cervical cancer.

Abstract

The implications of the studies of Victor Moreno and colleagues1Moreno V Bosch FX Muñoz N 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: 1085-1092Summary Full Text Full Text PDF PubMed Scopus (502) Google Scholar and Nubia Muñoz and colleagues (March 30, p 1093),2Muñoz N Franceschi S Bosetti C et al.Role of parity and human papillomavirus in cervical cancer: the IARC multicentric casecontrol study.Lancet. 2002; 359: 1093-1101Summary Full Text Full Text PDF PubMed Scopus (430) Google Scholar in which they show increases in cervical cancer related to long-term hormonal contraceptive use and multiparity in women with human papillomavirus (HPV) infection, should not be underestimated.The UK Department of Health reacted cautiously to the research, emphasing that regular cervical screening reduces the incidence of cervical cancer.3Adams S Long term use of oral contraceptives and risk of cervical cancer in women with high risk type human papillomavirus: memo CEM/CMO/2002/5. Department of Health, London2002Google Scholar This effect is correct but down-plays the anxiety experienced by women with abnormal smears who have to undergo further investigations. This anxiety may be greater than the fear of pregnancy, and women might be advised, and prefer, to switch periodically from oral contraceptives to condoms.The association between long-term hormonal contraception and cervical cancer is clearly important for developing countries, where cytological screening is largely unavailable and women are more likely to progress to cancer. Yet in developed countries, increasing evidence shows a link between steroid hormones and breast, cervical, and ovarian cancers. Women, therefore, deserve much clearer guidance about the risks associated with using hormonal contraceptives. Sex steroids can either promote carcinogenesis (oestrogen in breast cancer) or be protective (progesterone in ovarian cancer).Importantly, short-term use of hormonal contraceptives may be beneficial in adolescents, among whom prevalence of HPV infection is high. Evidence of significantly lower incidence of HPV infections in oralcontraceptive users than in non-users (odds ratio 0·54) has been reported in the USA.4Moscicki A-B Hills N Shiboski S et al.Risks for incident human papillomavirus and low grade squamous intraepithelial lesion development in young females.JAMA. 2001; 285: 2995-3002Crossref PubMed Scopus (472) Google Scholar Sex steroids may play a different part in infection and disease, which was also shown by Moreno and colleagues and Muñoz and colleagues, in an association between high parity and long-term contraception use with cervical cancer but not with persistence of HPV infection. Hormonal contraceptives may boost mucosal immunity in adolescence, when menstrual dysfunction is common and mean oestrogen concentrations are lower than those in older women.5Brabin L Interactions of the female environment, susceptibility to viral infections, and disease progression.AIDS Patient Care STDs. 2002; 16: 1-11Crossref PubMed Scopus (91) Google Scholar In mature women, IgG and secretory IgA increase in the follicular phase of the menstrual cycles, and IgA concentrations are higher in women taking oral contraceptives. Regularisation of menstrual patterns with hormonal contraceptive use could improve mucosal immunity, and, therefore, immunity to HPV infection, and lower the risk of cervical cancer in later life.In the presence of a persistent HPV infection, carcinogenesis is promoted by sex steroids, but whether the effects are due to oestrogen or progesterone is unclear. Cervical squamous epithelium contains oestrogen receptors that respond to chronic oestrogen administration. Persistent proliferation stimulated by long-term use of contraceptives could initiate progression to invasive cancer. Epithelial cells also bear progesterone receptors, and in these cells HPV gene expression may be boosted by progesterone-based contraceptives or pregnancy. Progesterone formulations have not been widely used in the UK, but injectable preparations are recommended for individuals deemed to be at high risk of pregnancy and sexually transmitted infections.Until specific sex-steroid interactions with infectious pathogens are identified, when HPV infection status is known, as in trials incorporating HPV screening, perhaps contraceptive use of women who are HPV positive should be monitored. The implications of the studies of Victor Moreno and colleagues1Moreno V Bosch FX Muñoz N 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: 1085-1092Summary Full Text Full Text PDF PubMed Scopus (502) Google Scholar and Nubia Muñoz and colleagues (March 30, p 1093),2Muñoz N Franceschi S Bosetti C et al.Role of parity and human papillomavirus in cervical cancer: the IARC multicentric casecontrol study.Lancet. 2002; 359: 1093-1101Summary Full Text Full Text PDF PubMed Scopus (430) Google Scholar in which they show increases in cervical cancer related to long-term hormonal contraceptive use and multiparity in women with human papillomavirus (HPV) infection, should not be underestimated. The UK Department of Health reacted cautiously to the research, emphasing that regular cervical screening reduces the incidence of cervical cancer.3Adams S Long term use of oral contraceptives and risk of cervical cancer in women with high risk type human papillomavirus: memo CEM/CMO/2002/5. Department of Health, London2002Google Scholar This effect is correct but down-plays the anxiety experienced by women with abnormal smears who have to undergo further investigations. This anxiety may be greater than the fear of pregnancy, and women might be advised, and prefer, to switch periodically from oral contraceptives to condoms. The association between long-term hormonal contraception and cervical cancer is clearly important for developing countries, where cytological screening is largely unavailable and women are more likely to progress to cancer. Yet in developed countries, increasing evidence shows a link between steroid hormones and breast, cervical, and ovarian cancers. Women, therefore, deserve much clearer guidance about the risks associated with using hormonal contraceptives. Sex steroids can either promote carcinogenesis (oestrogen in breast cancer) or be protective (progesterone in ovarian cancer). Importantly, short-term use of hormonal contraceptives may be beneficial in adolescents, among whom prevalence of HPV infection is high. Evidence of significantly lower incidence of HPV infections in oralcontraceptive users than in non-users (odds ratio 0·54) has been reported in the USA.4Moscicki A-B Hills N Shiboski S et al.Risks for incident human papillomavirus and low grade squamous intraepithelial lesion development in young females.JAMA. 2001; 285: 2995-3002Crossref PubMed Scopus (472) Google Scholar Sex steroids may play a different part in infection and disease, which was also shown by Moreno and colleagues and Muñoz and colleagues, in an association between high parity and long-term contraception use with cervical cancer but not with persistence of HPV infection. Hormonal contraceptives may boost mucosal immunity in adolescence, when menstrual dysfunction is common and mean oestrogen concentrations are lower than those in older women.5Brabin L Interactions of the female environment, susceptibility to viral infections, and disease progression.AIDS Patient Care STDs. 2002; 16: 1-11Crossref PubMed Scopus (91) Google Scholar In mature women, IgG and secretory IgA increase in the follicular phase of the menstrual cycles, and IgA concentrations are higher in women taking oral contraceptives. Regularisation of menstrual patterns with hormonal contraceptive use could improve mucosal immunity, and, therefore, immunity to HPV infection, and lower the risk of cervical cancer in later life. In the presence of a persistent HPV infection, carcinogenesis is promoted by sex steroids, but whether the effects are due to oestrogen or progesterone is unclear. Cervical squamous epithelium contains oestrogen receptors that respond to chronic oestrogen administration. Persistent proliferation stimulated by long-term use of contraceptives could initiate progression to invasive cancer. Epithelial cells also bear progesterone receptors, and in these cells HPV gene expression may be boosted by progesterone-based contraceptives or pregnancy. Progesterone formulations have not been widely used in the UK, but injectable preparations are recommended for individuals deemed to be at high risk of pregnancy and sexually transmitted infections. Until specific sex-steroid interactions with infectious pathogens are identified, when HPV infection status is known, as in trials incorporating HPV screening, perhaps contraceptive use of women who are HPV positive should be monitored.