Letter to the Editor
HPV types present in invasive cervical cancers of HIV-seropositive women
Article first published online: 6 JUN 2008
Copyright © 2008 Wiley-Liss, Inc.
International Journal of Cancer
Volume 123, Issue 5, pages 1224–1225, 1 September 2008
How to Cite
Strickler, H. D., Palefsky, J. M. and Burk, R. D. (2008), HPV types present in invasive cervical cancers of HIV-seropositive women. Int. J. Cancer, 123: 1224–1225. doi: 10.1002/ijc.23630
- Issue published online: 17 JUN 2008
- Article first published online: 6 JUN 2008
- Manuscript Accepted: 11 MAR 2008
- Manuscript Received: 4 MAR 2008
A recent report by De Vuyst et al.1 found that the prevalence of human papillomavirus (HPV) 16, the most important oncogenic HPV type, was similar in cervical cancer specimens obtained from HIV-seropositive and HIV-seronegative women in Kenya (41 and 44%, respectively). These data are important, since they suggest that current HPV vaccines containing HPV 16 and 18 (if effective in HIV-seropositive patients) have the potential to prevent many cancers in this and similar settings.
The findings were also something of a surprise. Prior reports had led to predictions that HPV 16 would be under-represented (and other oncogenic HPV types over-represented)in cervical cancer specimens among HIV-seropositivecompared with HIV-seronegative women. In particular, a meta-analysis of studies from around the world found that HPV 16 was significantly less prevalent in high grade squamous intraepithelial lesions (HSILs) from HIV-seropositive women than in the general female population,2 and two large, independent cohorts found that the prevalence of HPV 16 was more weakly associated with CD4+ T-cell count than the prevalence of any other HPV type.3 HPV 16's relative independence from immune status in these studies has been interpreted as evidence that HPV 16 may be innately better than other HPV types at avoiding the effects of immune surveillance and, thereby, less affected by changes in immune status.
The disconnect between these prior reports and the study in Kenya can have several possible explanations, including: (i) The prior data showing a weak association of HPV 16 with host immune status were incorrect; (ii) The HPV 16-immune status association is (as reported) weak during the early stages of cervical tumorigenesis. However, it is the accumulation of relevant genetic mutations that is most important in the etiopathogenesis of frank carcinoma; (iii) The differences in HPV natural history between HIV-seropositive and HIV-seronegative women is not as strong in Kenya as it is in Europe and North America.
The latter explanation may be the most likely (and most intriguing). Micronutrient deficiencies and chronic infections, especially helminthic infections, are common in many developing economic settings, and can create a relative immunosuppressive state.4 This might make HIV-seronegative women less immunologically distinct from HIV-seropositivewomen, and could, in theory, contribute to the high cervical cancer rates common in such settings. The authors, in fact, correctly point out that studies in Africa have often found weaker associations between cervical cancer and HIV/AIDS than have been reported in Europe and North America.
It is also possible, however, that technical issues have led to underestimation of the effects of HIV/AIDS on risk of cervical cancer in Africa. The only truly population-based study (e.g., involving linkage between a cancer registry and AIDS registry; similar to those conducted in the US5, 6) found a significant association between HIV/AIDS and risk of cervical cancer in Uganda.7 Moreover, De Vuyst et al. were careful to point to a limitation to their data: more than half of subjects had high CD4+ T-cell counts, further reducing the potential differences between the HIV-seropositive and HIV-seronegative women. It is noteworthy, therefore, that a study in Zambia which involved a larger fraction of women with low CD4+ T-cell counts, found that HPV 52 was the most common HPV type present in 28 cervical cancer cases, followed equally by HPV 58 and HPV 16.8
Because of the potential importance of such data to HPV vaccine strategies, as well as to our understanding of the carcinogenicity of HPV 16, we feel additional studies similar to the one conducted by De Vuyst et al., should be conducted in different populations, and should include women with a range of CD4+ T-cell counts. For the reasons given above, we predict that HPV 16 DNA will be underrepresented in cervical cancer specimens among HIV-seropositive women in Europe and North America, and to a lesser degree in developing economic settings; e.g., due to a higher frequency of immunosuppression in their general populations, and competing risks of death. Through collaboration with the AIDS and Cancer Specimen Resource (ACSR) of the National Cancer Institute and others in the US, our group has been collecting cervical cancer specimens from HIV-seropositive women for type-specific HPV DNA testing in this country, and wish to encourage researchers with access to relevant specimens in other developed and developing economic settings to do the same.
- 1Human papillomavirus types in women with invasive cervical carcinoma by HIV status in Kenya. Int J Cancer 2008; 122: 244–6., , , , , .
- 2Human papillomavirus types among women infected with HIV: a meta-analysis. Aids 2006; 20: 2337–44., , .
- 3Human papillomavirus type 16 and immune status in human immunodeficiency virus—seropositive women. J Natl Cancer Inst 2003; 95: 1062–71., , , , , , , , , , , , et al.
- 4Immune modulation by helminthic infections: worms and viral infections. Parasite Immunol 2006; 28: 483–96., .
- 5Spectrum of AIDS-associated malignant disorders. Lancet 1998; 351: 1833–9., , , , , , , .
- 6Immune deficiency and risk for malignancy among persons with AIDS. J Acquir Immune Defic Syndr 2003; 32: 527–33., , , .
- 7Spectrum of cancers among HIV-infected persons in Africa: the Uganda AIDS-Cancer Registry Match Study. Int J Cancer 2006; 118: 985–90., , , , , , , , .
- 8Prevalence and distribution of HPV genotypes among HIV-infected women in Zambia. Br J Cancer 2007; 96: 1480–3., , , , , , .
Howard D. Strickler, Joel M. Palefsky, Robert D. Burk.