Human Immunodeficiency Virus (HIV)- and Non-HIV-Associated Immunosuppression and Risk of Cervical Neoplasia.

OBJECTIVE To estimate the risk of cervical intraepithelial neoplasia grade 2, 2-3, 3, adenocarcinoma in situ, or cancer (CIN 2 or worse) among women with human immunodeficiency virus (HIV)- and non-HIV-associated immunosuppression. METHODS We performed a case-control study of 20,146 women with incident CIN 2 or worse and 5:1 age-matched, incidence-density selected women in a control group (n=100,144) enrolled in an integrated health care system from 1996 to 2014. Adjusted rate ratios (RRs) from conditional logistic regression were obtained for HIV status (stratified by CD4 T-cells), solid organ transplant history, and immunosuppressive medication use. RESULTS Risk of CIN 2 or worse was increased among women with HIV (n=36 women in the case group and 79 women in the control group; adjusted RR 2.0, 95% CI 1.3-3.0) compared with those without HIV and in solid organ transplant recipients (n=51 women in the case group and 68 women in the control group; RR 3.3, 95% CI 2.3-4.8) compared with women without a prior transplant. The highest risks were among women with HIV and less than 200 CD4 T-cells/microliter (n=9 women in the case group and eight women in the control group; RR 5.6, 95% CI 2.1-14.7) compared with those without HIV and in solid organ transplant recipients prescribed three or greater immunosuppressive medication classes (n=32 women in the case group and 33 women in the control group; RR 4.1, 95% CI 2.5-6.8) compared with women without a prior transplant and zero medication classes. No increased risks were observed for women with HIV and 500 or greater CD4 T-cells/microliter (n=9 women in the case group and 43 women in the control group; RR 0.8, 95% CI 0.4-1.7) compared with those without HIV or women without prior solid organ transplantation prescribed two or fewer immunosuppressive medication classes (n=1,262 women in the case group and 6,100 women in the control group; RR 0.95, 95% CI 0.89-1.01) compared with women without and a prior transplant and zero medication classes. CONCLUSION Risk of CIN 2 or worse is increased in women with a prior solid organ transplant or who have HIV and CD4 cells/microliter less than 500 but not in women with HIV and higher CD4 levels or in women without a prior solid organ transplant but who are prescribed only one or two immunosuppressive medication classes.

[1]  S. Nakagawa,et al.  Clinical outcomes of abnormal cervical cytology and human papillomavirus-related lesions in patients with organ transplantation: 11-year experience at a single institution , 2016, International Journal of Clinical Oncology.

[2]  S. Arron,et al.  Sirolimus use and risk of cutaneous squamous cell carcinoma (SCC) in solid organ transplant recipients (SOTRs). , 2015, Journal of the American Academy of Dermatology.

[3]  H. Strickler,et al.  Incidence of cervical precancers among HIV-seropositive women. , 2015, American journal of obstetrics and gynecology.

[4]  E. Barnes,et al.  Are Patients with Inflammatory Bowel Disease on Chronic Immunosuppressive Therapy at Increased Risk of Cervical High-grade Dysplasia/Cancer? A Meta-analysis , 2014, Inflammatory bowel diseases.

[5]  M. Goodman,et al.  HPV‐Related Cancers After Solid Organ Transplantation in the United States , 2013, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[6]  Richard D Moore,et al.  Invasive Cervical Cancer Risk Among HIV-Infected Women: A North American Multicohort Collaboration Prospective Study , 2013, Journal of acquired immune deficiency syndromes.

[7]  P. Castle,et al.  Safety against cervical precancer and cancer following negative human papillomavirus and Papanicolaou test results in human immunodeficiency virus-infected women. , 2012, Archives of internal medicine.

[8]  T. Pruett.  Spectrum of Cancer Risk Among US Solid Organ Transplant Recipients , 2012 .

[9]  D. Klein,et al.  HIV Infection, Immunodeficiency, Viral Replication, and the Risk of Cancer , 2011, Cancer Epidemiology, Biomarkers & Prevention.

[10]  M. Candiani,et al.  Cervical Human Papillomavirus in transplanted Italian women: a long-term prospective follow-up study. , 2011, Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology.

[11]  E. Klumb,et al.  Are women with lupus at higher risk of HPV infection? , 2010, Lupus.

[12]  A. Hoitsma,et al.  Skin cancer and (pre)malignancies of the female genital tract in renal transplant recipients , 2010, Transplant international : official journal of the European Society for Organ Transplantation.

[13]  Bryan Langholz,et al.  Case-control studies = odds ratios: blame the retrospective model. , 2010, Epidemiology.

[14]  A. Barrett,et al.  Increased risk of cervical dysplasia in long-term survivors of allogeneic stem cell transplantation--implications for screening and HPV vaccination. , 2008, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[15]  K. Anastos,et al.  Incidence of cervical squamous intraepithelial lesions associated with HIV serostatus, CD4 cell counts, and human papillomavirus test results. , 2005, JAMA.

[16]  P. Chan,et al.  Increased prevalence of squamous intraepithelial lesions in systemic lupus erythematosus: association with human papillomavirus infection. , 2004, Arthritis and rheumatism.

[17]  H. Adami,et al.  Cancer risk following organ transplantation: a nationwide cohort study in Sweden , 2003, British Journal of Cancer.

[18]  B. Einollahi,et al.  Uterine cervical intraepithelial neoplasia in renal transplantation. , 2001, Transplantation proceedings.

[19]  S. Krishna,et al.  Cervical intraepithelial neoplasia and human papilloma virus infection in renal transplant recipients. , 2001, Indian journal of cancer.

[20]  M. Peterson,et al.  Increased cervical dysplasia in intravenous cyclophosphamidetreated patients with SLE: a preliminary study , 2000, Lupus.

[21]  Y. Erhan,et al.  Evaluation of the risk of cervical intraepithelial neoplasia and human papilloma virus infection in renal transplant patients receiving immunosuppressive therapy. , 1999, European journal of gynaecological oncology.

[22]  J. Rischen‐Vos,et al.  The incidence of cervical intraepithelial neoplasia among women with renal transplant in relation to cyclosporine , 1995, British journal of obstetrics and gynaecology.

[23]  M M Duffy,et al.  Immunosuppressive medications. , 1993, The South Carolina nurse.

[24]  K. Mclaren,et al.  Human papillomavirus infection and cervical intraepithelial neoplasia in women with renal allografts. , 1989, BMJ.

[25]  J. Briggs,et al.  Cervical Intraepithelial Neoplasia in Immunosuppressed Women after Renal Transplantation , 1980, Scottish medical journal.