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Saudi Journal of Kidney Diseases and Transplantation
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Table of Contents   
ORIGINAL ARTICLE  
Year : 2011  |  Volume : 22  |  Issue : 3  |  Page : 433-436
Human papilloma virus infection in female kidney transplant recipients


1 Department of Obstetrics and Gynecology, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran
2 Nephrology Research Center, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran
3 Department of Neurology, Mashad University of Medical Science, Mashad, Iran

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Date of Web Publication7-May-2011
 

   Abstract 

The objective of this study was to evaluate the incidence of genital human papilloma virus (HPV) infection and cervical intra-epithelial lesions in transplanted patients. Cervical Papanicolaou (Pap) smear/HPV test and colposcopic examinations were performed in 58 patients who were candidates for renal transplant surgery; these tests were repeated one year later. Their age range was 26-53 years (mean, 37.2 years). Hypertension was the most common cause of renal insufficiency (34.4%), while in 41.4% of the patients, the causative pathology was unknown. In 24.1% of the patients, there was no history of dialysis, i.e. they had pre-emptive transplantation. The mean duration of marriage (years since first intercourse) was 16.2 years (range, 1-35). Coitus interruptus was the most common contraceptive method used (37.9%), followed by tubal ligation and condom (10.3% and 6.9%, respectively). All patients had negative Pap tests and normal gynecologic exam before undergoing transplantation. The Pap test remained normal after transplant surgery, although the HPV test became positive in four patients (6.9%). There were five cases of white epithelium on colposcopy, but biopsy showed normal metaplasia. Two cases of extensive anogenital warts were treated by CO 2 laser, and one patient had recurrent warts, which responded well to second laser surgery. None of the study patients had squamous intra-epithelial lesions (SIL) or vulvar intra-epithelial neoplasia. Our study suggests that screening with HPV and Pap test should be performed before transplant surgery and should be repeated at regular intervals in order to avoid irreversible situations such as high-grade SILs, which are difficult to treat. Avoiding high-risk sexual relations in this group of patients is highly recommended.

How to cite this article:
Ghazizadeh S, Lessan-Pezeshki M, Nahayati MA. Human papilloma virus infection in female kidney transplant recipients. Saudi J Kidney Dis Transpl 2011;22:433-6

How to cite this URL:
Ghazizadeh S, Lessan-Pezeshki M, Nahayati MA. Human papilloma virus infection in female kidney transplant recipients. Saudi J Kidney Dis Transpl [serial online] 2011 [cited 2019 Apr 24];22:433-6. Available from: http://www.sjkdt.org/text.asp?2011/22/3/433/80476

   Introduction Top


Kidney transplantation is the best and most effective option for patients with severe renal damage to restore their health and help in recovering their sexual and reproductive functions. There has been ongoing improvement in survival and quality of life after kidney transplantation.

However, immunosuppressed allograft recipients are at a high risk of certain infections such as human papilloma virus (HPV) and its related malignancies, especially uterine cervical intra-epithelial neoplasia. This lesion can be investigated by screening methods such as Papanicolaou (Pap) and HPV tests and colposcopy before and after transplant surgery. The purpose of this study was to evaluate the incidence of genital HPV infection and cervical intra-epithelial lesions in transplanted patients.


   Materials and Methods Top


Our study involved 58 female kidney transplant recipients. They were examined by a gynecologist to check for warts in the anogenital area before surgery. All of them underwent HPV/Pap tests; colposcopy was performed only if deemed necessary. HPV/Pap tests were repeated one year after the surgery. All patients underwent colposcopy and a biopsy was taken if there were abnormal findings.


   Results Top


The age range was 26-53 years (mean, 37.2 years). Hypertension was the most common cause of renal insufficiency (34.4%), while in 41.4% of the patients, the causative pathology was unknown. In 24.1% of the patients, there was no history of dialysis, i.e. they had pre-emptive transplantation. The mean duration of marriage (years since first intercourse) was 16.2 years (range, 1-35). Coitus interruptus was the most common contraceptive method used (37.9%), followed by tubal ligation and condom (10.3% and 6.9%, respectively). All patients had negative HPV/Pap tests and normal gynecologic examination before undergoing transplantation. The Pap test remained normal after transplant surgery while the HPV test became positive in four patients (6.9%). There were five cases of white epithelium on colposcopy; biopsy showed normal metaplasia. Two cases of extensive anogenital warts were treated with CO 2 laser, while one patient had recurrent warts, which responded well to second laser surgery. None of the study patients had squamous intra-epithelial lesions (SIL) or vulvar intra-epithelial neoplasia (VIN).


   Discussion Top


The HPV is responsible for an enormous global burden of genital disease. HPV is associated with 500,000 new cases of cervical cancer and 250,000 deaths due to cervical cancer worldwide, each year. Oncogenic HPV types 16 and 18 are responsible for the majority of cervical cancers and can also cause low- and high-grade cervical lesions as well as high-grade vulvar or vaginal intra-epithelial neoplasia (VIN or VaIN 2/3). Non-oncogenic types of HPV 6 and 11 also contribute to the overall burden of HPV disease, causing low SIL, anogenital warts, cutaneous lesions and respiratory papillomatosis. [1] The risk factors for HPV infection include younger age at the time of initiation of sexual activity, sexual behavior, intact foreskin and immunologic status. [2]

A quadrivalent prophylactic vaccine against HPV-6, -11, -16 and -18 is currently available, which is highly effective in preventing persistent HPV infection and pre-cancerous lesions caused by vaccine-specific HPV. HPV vaccine is currently indicated for girls aged 9-26 years, but ongoing trials are evaluating the efficacy in other populations. [3]

The largest experience on the relative incidence and types of malignancy among organ transplant recipients comes from an analysis of over 35,000 first-time renal transplant recipients. [4] Among the neoplasms that are markedly increased in frequency in solid organ transplant recipients are skin cancer (squamous cell carcinoma, basal cell cancers, melanomas and Merkel cell cancers), non-Hodgkin's and Hodgkin's lymphomas, Kaposi's sarcoma, in situ carcinoma of the uterine cervix, ano-genital cancers, renal cell carcinoma, cancers of the pharynx, larynx, or oral cavity and hepatocellular carcinomas. [5]

Cancers involving the ano-genital region (i.e., anus, vulva, perianal region, penis, scrotum or perineum) account for two to three percent of the cancers in transplant recipients. Lesions tend to be multiple and/or extensive, particularly in women, one-third of whom have concurrent cervical cancer. Clinically, these lesions often appear as pigmented papular lesions, but they may resemble genital warts. [6]

Cyclosporine may promote cancer progresssion, principally via the production of transforming growth factor-beta (TGF-beta). Tacrolimus also appears to increase TGF-beta levels. In humans, sirolimus, compared with other immunosuppressive medications, may confer a decreased risk of malignancy. [7] In a study using data from two large registries, there was a non-significant trend to a decreased risk with mycophenolate versus non-mycophenolate-based therapy. [8] The principal mechanism of a lower risk of malignancy with mycophenolate mofetil, to the degree that it occurs, may be due to the decreased incidence of acute rejections. This results in a reduced need for increased doses of immunosuppressive agents.

Paternoster et al reported a higher incidence of lower female genital tract intra-epithelial lesions when compared with the general population. They showed a constant association between high-risk HPV infection and gynecologic intra-epithelial neoplasia, whereas there was no association between low-risk HPV infection and neoplasia. [9] In our study, the incidence of HPV infection was zero before transplant surgery, but it increased to 6.9% later. We did not have any patients with intra-epithelial neoplasia.

Ozsaran et al found HPV in two of their 48 renal transplant patients. [10] Seshadri et al, in a prospective study of 42 renal transplant recipients with age 41 years and parity matched controls, found histological evidence of HPV in 24 and SIL in ten women in the immunosuppressed group and HPV infection in 13 and SIL in three women in the control group (odds ratio of 6.1). More women in the immunosuppressed group had SIL of higher degree; interestingly, cytology did not pick up HPV infection in any of them. [11]

Altamirano et al reported a case of a 17-year-old female kidney transplant recipient. Urine smears showed the presence of koilocytes. Polymerase chain reaction performed on material retrieved from both the smears showed HPV18 DNA sequences. They suggested that urinary cytology may prove useful for routine search of cells with the cytopathic effect of this virus. [12] In conclusion, HPV and Pap test screening should start before planned transplant surgery, and they should be repeated at regular intervals in order to avoid irreversible situations such as high-grade SILs that are difficult to treat; colposcopy and direct biopsy might also be necessary. Avoiding high-risk sexual relations in this group of patients is highly recommended.

 
   References Top

1.Paavonen J. Human papillomavirus infection and the development of cervical cancer and related genital neoplasias. Int J Infect Dis 2007;11:53-9.  Back to cited text no. 1
    
2.Mayeaux EJ Jr. Reducing the economic burden of HPV-related diseases. J Am Osteopath Assoc 2008;108:S2-7.  Back to cited text no. 2
[PUBMED]  [FULLTEXT]  
3.McIntosh J, Sturpe DA, Khanna N. Human papillomavirus vaccine and cervical cancer prevention: practice and policy implications for pharmacists. J Am Pharm Assoc (2003) 2008;48:e1-13;quiz e14-7.  Back to cited text no. 3
    
4.Kasiske B, Snyder J, Gilbertson D, Wang C. Cancer after kidney transplantation in the United States. Am J Transplant 2004;4:905-13.  Back to cited text no. 4
    
5.Saeian K, Franco J, Komorowski R, Adams M. Hepatocellular carcinoma after renal transplantation in the absence of cirrhosis or viral hepatitis: a case series. Liver Transpl Surg 1999;5:46-9.  Back to cited text no. 5
    
6.Adami J, Gabel H, Lindelof B, Ekstrom K, Granath F. Cancer risk following organ transplantation: a nationwide cohort study in Sweden. Br J Cancer 2003;89:1221-7.  Back to cited text no. 6
    
7.Guba M, Steinbauer M, Koehl G, et al. Rapamycin inhibits primary and metastatic tumor growth by antiangiogenesis: involvement of vascular endothelial growth factor. Nat Med 2002;8:128-35.  Back to cited text no. 7
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8.Robson R, Cecka J, Opelz G, Budde M, Sacks S. Prospective registry-based observational cohort study of the long-term risk of malignancies in renal transplant patients treated with mycophenolate mofetil. Am J Transplant 2005; 5:2954-60.  Back to cited text no. 8
    
9.Paternoster DM, Cester M, Resente C, et al. Human papilloma virus infection and cervical intraepithelial neoplasia in transplanted patients. Transplant Proc 2008;40:1877-80.  Back to cited text no. 9
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10.Ozsaran AA, Ates T, Dikmen Y, et al. Evaluation of the risk of cervical intraepithelial neoplasia and human papilloma virus infection in renal transplant patients receiving immunosuppressive therapy. Eur J Gynaecol Oncol 1999; 20:127-30.   Back to cited text no. 10
    
11.Seshadri L, George SS, Vasudevan B, Krishna S. Cervical intraepithelial neoplasia and human papilloma virus infection in renal transplant recipients. Indian J Cancer 2001;38:92-5.   Back to cited text no. 11
    
12.Altamirano E, Drut R. Koilocytes in urinary cytology in a patient with kidney transplant. Diagn Cytopathol 2008;36:338-40.  Back to cited text no. 12
[PUBMED]  [FULLTEXT]  

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Correspondence Address:
Shirin Ghazizadeh
Professor, Obstetrician & Gynecologist, Department of Obstetrics and Gynecology, Imam Khomeini Hospital, Tehran University of Medical Sciences, Keshavarz Blvd, Tehran 14197
Iran
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PMID: 21566296

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    Abstract
    Introduction
    Materials and Me...
    Results
    Discussion
    References
 

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