The number of solid organ transplants in the United States rises annually, with 36,429 performed in 2018, of which 13,904 recipients were female.1 As survival after transplant continues to improve, understanding the long-term effects of required immunosuppression is increasingly important for improving length and quality of life. Women who are immunosuppressed after solid organ transplantation are at an increased risk for many malignancies, including lower genital tract cancers, which include cervical, vulvar, vaginal, and anal cancers.2 Although there are many factors that play a role in the increased incidence of different cancers, for lower genital tract cancers specifically, the increased risk is a result of the effects of immunosuppression on the clearance of high-risk human papillomavirus (HPV).2,3 Almost all cervical cancers, more than 50% of vulvar cancers, 70% of vaginal cancers, and 90% of anal cancers are attributable to high-risk HPV viruses.4–8 Human papillomavirus’ persistence plays a critical role in progression to lower genital tract cancers, and therefore the reduced ability to immunologically control this virus places these patients at increased risk.
Among healthy women, the 5-year cumulative risk of high-grade cervical intraepithelial neoplasia (CIN 2 or worse) is 1.7%, and the 5-year cumulative risk of invasive cervical cancer is 0.049%.9 Data on the incidence of noncervical lower genital tract dysplasia in healthy women are less well-described because there is no widely available screening test for these types of dysplasia. One study found the incidence of in situ vulvar carcinoma in 2000 was 2.86 cases per 100,000 women.10 Another calculated the incidence of in situ anal carcinoma from 1994 to 2000 was 0.22 cases per 100,000 women.11 Although most studies suggest an increased risk of lower genital tract cancers and cervical dysplasia in women who have undergone transplantation, there are minimal data on other, noncervical lower genital tract dysplasia. The largest study on HPV-associated cancer after transplant, the U.S. Transplant Cancer Match study, demonstrated a significantly increased incidence of invasive HPV-associated cancers after transplant, particularly for vulvar (standardized incidence ratio 7.3) and anal (standardized incidence ratio 5.4) cancers.12 There was no increased risk of invasive cervical cancer identified in this analysis (standardized incidence ratio 1.0). A meta-analysis comparing HPV disease among women with human immunodeficiency virus (HIV) to solid organ transplant recipients found a similarly increased risk in both populations, revealing a significant risk for vulvar and vaginal cancer (standardized incidence ratio 22.76), anal cancer (standardized incidence ratio 4.85), and cervical cancer (standardized incidence ratio 2.13) among transplant recipients.13 Some studies have also examined the risk of cervical dysplasia in transplant recipients, with one study suggesting up to a sixteen-fold increased risk of CIN in patients who have undergone renal transplantation.3 Other studies have also demonstrated an increased risk of CIN 2 or worse among transplant recipients, with one suggesting an approximately threefold increased risk of CIN 2 or worse compared with the general population.14–24 However, the prevalence of CIN among transplant recipients varies significantly from study to study, with some finding the prevalence as low as 3.3% or as high as 49%.20,23 One study estimated the overall 1-year, 3-year, and 5-year incidence rates of genital dysplasia (including cervical, vaginal, and vulvar dysplasia) were 1.3, 3.3, and 4.8% respectively and for CIN alone the incidence rates were 1.3, 2.7, and 4.2% respectively.15 Studies have also suggested an increased risk of vulvar, vaginal, and anal intraepithelial neoplasia (VIN, VAIN, and AIN, respectively),14–17 but there is a paucity of data regarding development of noncervical lower genital tract dysplasia among transplant recipients. There are also minimal data on specific clinical and pathologic risk factors for developing lower genital tract dysplasia after transplant.
In this retrospective study, we sought to evaluate the cumulative incidence of lower genital tract dysplasia or cancers after solid organ transplant, to identify risk factors for development of disease and to assess the time to high-grade dysplasia or cancer. Understanding these factors will help guide evidence-based screening recommendations and treatment of dysplasia in this high-risk population.
This was a retrospective study of adult female patients who underwent solid organ transplantation at a large academic institution between January 1, 2000, and December 31, 2015. We included women who had at least 2 years of documented follow-up after their first transplant and had at least one cervical or lower genital tract pathology specimen available in our institutional pathology archive from either before or after transplant. Specimens included Pap test, endocervical curettage, cervical biopsy, loop electrosurgical excision procedure (LEEP) specimen, conization specimen, anal Pap test, anal biopsy, vulvar biopsy, or vaginal biopsy.
Patients were identified via the institutional pathology archive and then cross-validated with a list of solid organ transplant recipients. Electronic medical record review was used to ensure patients met the inclusion criteria. All female patients meeting inclusion criteria were eligible for the study. Patients who underwent a total hysterectomy before their first transplant were excluded if they had no other lower genital tract pathology specimens after transplantation. Through chart review, patients' clinical data, including medical and transplant history, demographic data, gynecologic history, and results of gynecologic exams (including cervical and lower genital tract pathology specimens and HPV tests), were extracted from patients' electronic medical records using a standardized extraction form. The institutional review board at our institution approved the study.
Descriptive statistics were reported as means with SDs, medians with interquartile ranges, frequencies, and percentages as indicated. Cumulative incidence of lower genital tract dysplasia and cancer in the overall population was calculated (based on gold standard tissue diagnosis). Findings of abnormal screening tests and genital warts (as per clinical documentation or pathologic diagnosis) were also reported. Patient demographics including age at first transplant, race, body mass index (calculated as weight in kilograms divided by height in meters squared), parity, history of HIV or prior immunosuppression, and smoking status were tabulated. Cervical screening before transplant—unknown screening history, normal screening, and abnormal screening—was determined through review of cervical cytology specimens available in the pathology archive. Transplant history including the transplanted organ, number of transplants, and indication for transplant were also determined. Owing to the high number of patients who underwent kidney transplant in this population, specific indication for kidney transplant was included; however, given the limited numbers of other organ transplants, specific indications were not included. Years of follow-up after transplant were also calculated. Missing data are reported as unknown directly in the table or in the footnote, as indicated. Univariate analyses were performed using logistic regression to calculate odds ratios (ORs) with 95% CIs to identify associations with the development of lower genital tract dysplasia (CIN, VAIN, VIN, or AIN). Multivariable logistic regression was then performed to determine independent associations with lower genital tract dysplasia using significant explanatory variables from univariate analysis. This multivariate analysis included age at first transplant, race, history of abnormal Pap test result, organ of first transplant, number of transplants, hydroxychloroquine use, and follow-up time after transplant. Year of transplant was excluded owing to collinearity with follow-up time, and indication for kidney transplant was excluded owing to overlap with organ of first transplant and hydroxychloroquine use. Owing to the limited number of adverse outcomes (n=47), a limited multivariable logistic regression was also performed using only five explanatory variables to improve power of the analysis. In this analysis, organ of first transplant and number of transplants were excluded owing to their weaker association with lower genital tract dysplasia.
The women who developed advanced or high-grade dysplasia were then analyzed separately. Patients who developed high-grade dysplasia or cancer were separated into noncervical lower genital tract dysplasia (VIN, VAIN, or AIN 2 or worse) and cervical dysplasia (CIN 2 or worse) for analysis. Calculations were performed for median time from first and most recent transplant to development of high-grade dysplasia or cancer diagnosis, and median total follow-up time after high-grade diagnosis. Procedures to treat dysplasia, including LEEPs, conizations, excisions, and resections, were also noted. Survival curves were created to demonstrate the probability of dysplasia as a function of time after first transplant for all lower genital tract dysplasia and all high-grade dysplasia. Significance was set to an alpha of 0.05. Analyses were performed using STATA 12.0.
In total, 513 female transplant recipients were identified using the pathology archive, and 84 were subsequently excluded because they had undergone a hysterectomy before transplantation and had no lower genital tract tissue specimens available after transplant. An additional 35 patients were excluded because they did not have at least 2 years of follow-up after transplant, leaving a total of 394 patients. The median age of these 394 women was 41 years (interquartile range 29–53) (Table 1). Of the 394 women in the study population, 47 (11.9%; 95% CI 8.8–15.9%) developed lower genital tract dysplasia, including cervical, vaginal, vulvar, or anal dysplasia over a median follow-up of 7.8 years (interquartile range 4.6–12.9) after first transplant. In this population, 38 (9.6%) developed cervical dysplasia, and 19 (4.8%) developed noncervical lower genital dysplasia. Ten (2.5%) patients developed both cervical and noncervical lower genital tract dysplasia (Fig. 1). Two hundred thirty-nine women (60.7%) had at least one documented Pap test before transplantation, and, of these, 43 (18.0%) had at least one abnormal Pap test result (Table 1). Sixty-one women (15.5%) had an HPV cotest with a Pap test before transplantation, and, of these, 17 (27.9%) had at least one positive HPV cotest. Three-hundred fourteen women (79.7%) had at least one Pap test after transplant. Nineteen (4.8%) women had a noncervical lower genital tract pathology specimen after transplant. One hundred seventy-four (44.2%) patients had an HPV cotest after transplant, of which 55 (31.6%) were positive. Thirty-three (8.4%) patients developed genital warts after transplant.
On univariate analysis, factors associated with increased risk of developing lower genital tract dysplasia included black or African American race (OR 2.47, 95% CI 1.26–4.85), lupus nephritis as an indication for kidney transplant (OR 5.47, 95% CI 1.89–15.83), another disease indication for kidney transplant (not diabetes or hypertension) (OR 2.31, 95% CI 1.02–5.25), receiving more than one transplant (OR 2.34, 95% CI 1.24–4.41), the use of the immunosuppressant hydroxychloroquine (OR 5.35, 95% CI 1.96–14.57), first transplant before 1986 (OR 7.70; 95% CI 1.04–56.95), and longer follow-up time after transplantation (OR 1.05, 95% CI 1.01–1.09). Factors associated with a reduced risk of developing lower genital tract dysplasia included receiving a liver at first transplant (OR 0.20, 95% CI 0.05–0.84), older age (OR 0.98, 95% CI 0.96–1.00) and a history of only normal Pap test results before transplant (OR 0.49, 95% CI 0.25–0.95) (Table 2). On multivariate analysis, black or African American race was significantly associated with an increased risk of developing lower genital tract dysplasia (OR 2.86, 95% CI 1.33–6.13), as was the use of hydroxychloroquine (OR 5.95, 95% CI 1.96–18.09) (Table 2). Results of the limited multivariable analysis were similar, with both black race and hydroxychloroquine use significantly associated with lower genital tract dysplasia (Table 2).
High-grade dysplasia or cancer was detected in 6.1% of women (n=24) at a median of 6.48 years (interquartile range 2.27–8.76) after first transplant, accounting for 51.1% of all lower genital tract dysplasia cases. Eleven women (2.8%) developed only high-grade cervical dysplasia or cancer (CIN 2 or worse), 10 (2.5%) developed only noncervical high-grade lower genital tract dysplasia or cancer (VIN, VAIN, AIN 2 or worse), and three women (0.8%) developed both high-grade cervical and high-grade noncervical lower genital tract dysplasia. There were six cases (1.5%) of carcinoma in the population. Among the 14 patients with CIN 2 or worse, one (7.1%) was diagnosed with cervical cancer; 5 of the 13 (38.5%) with VAIN, VIN, or AIN 2 or worse were diagnosed with lower genital tract cancers. This amounts to at least a 1.3% prevalence of noncervical lower genital tract cancer in this population (Fig. 1).
For the 14 patients that developed CIN 2 or worse after transplant, the median time from first transplant to CIN 2 or worse diagnosis was 3.95 years (interquartile range 2.13–7.02) and the median follow-up period after CIN 2 or worse diagnosis was 4.08 years (interquartile range 2.69–9.29) (Fig. 2). Three women developed CIN 2 or worse after a second transplant, and the median time from most recent transplant to CIN 2 or worse diagnosis was 3.18 years (interquartile range 1.98–6.28). Notably, of all CIN 2 or worse cases, 71.4% (n=10) developed within 5 years after their most recent transplant. The patient who developed invasive squamous cell carcinoma of the cervix was diagnosed 8.48 years after transplant. Pap tests before transplant was unknown for 8 of these 14 women (57.1%). Two patients who developed CIN 2 or worse had known abnormal Pap test results before transplantation. One had an atypical squamous cells of undetermined significance Pap test result 7 years before transplant, and a subsequent no intraepithelial lesion and HPV-negative screen result; the other had a low-grade squamous intraepithelial lesion Pap test result 1 year before transplant, with a repeat Pap test result 5 months before transplant that was no intraepithelial lesion.
Of the 14 women with high-grade cervical dysplasia, 12 (85.7%) underwent a LEEP or conization for treatment of CIN 2 or worse; two of whom also underwent hysterectomy. Two (14.3%) had no known definitive treatment of their dysplasia. Eight of the 14 (57.14%) patients with CIN 2 or worse had resolution of their disease with treatment and continued to have no evidence of dysplasia at most recent follow-up. Of the six with evidence of CIN at the most recent follow-up, four had previously had a LEEP or conization and continued to have persistent CIN.
Four of the 14 women with high-grade cervical dysplasia (28.6%) also developed other concurrent lower genital dysplasia: one developed anal squamous cell carcinoma; one developed VIN 2 or worse, VAIN 1, and AIN 3; one developed VIN 3, VAIN 2 or worse, and AIN 3; and one developed AIN 1. In all four patients, CIN 2 or worse was diagnosed before the detection of the additional lower genital tract dysplasia or cancer, with an average time of 2.87 years (SD 2.24 years) between the first CIN 2 or worse diagnosis and the first additional lower genital tract dysplasia diagnosis.
For the 13 patients (3.3%) who developed VAIN, VIN, or AIN 2 or worse, the median time from transplant to VAIN, VIN, or AIN 2 or worse diagnosis was 7.41 years (interquartile range 3.94–11.91) (Fig. 2). Five of these 13 patients developed VAIN, VIN, or AIN 2 or worse after a second or third transplant, and the median time from the most recent transplant to VAIN, VIN, or AIN 2 or worse diagnosis was 3.94 years (interquartile range 2.69–6.49). Eight of these 13 (61.5%) women developed VAIN, VIN, or AIN 2 or worse within 5 years of their most recent transplant. The median follow-up time after diagnosis was 3.81 years (interquartile range 1.68–6.90).
Five (38.5%) of the 13 patients with high-grade noncervical lower genital tract dysplasia developed lower genital tract cancer: three developed anal squamous cell carcinoma, one developed vaginal squamous cell carcinoma, and one developed vulvar squamous cell carcinoma. The median time from first transplant to cancer diagnosis was 7.41 years (interquartile range 6.47–14.89). The median time from most recent transplant to cancer diagnosis was 3.63 years (interquartile range 2.00–6.47).
Twelve of the 13 patients (92.3%) with VAIN, VIN, or AIN 2 or worse had at least one procedure for management of dysplasia including an excision, resection, ablation, or vulvectomy, and 12 of the 13 patients (92.3%) had persistent dysplasia at most recent follow-up. Six women (46.2%) developed CIN, three of whom developed CIN 2 or worse, and in no case was noncervical lower genital tract dysplasia diagnosed before CIN.
In this retrospective study, lower genital tract dysplasia occurred in 11.9% of the study population, high-grade dysplasia occurred in 4.6%, and invasive lower genital tract cancers occurred in 1.5%. Importantly, 2.0% of the population developed high-grade noncervical dysplasia, and noncervical lower genital tract cancers occurred in 1.3% of the population overall. These high-grade noncervical dysplasias tended to persist and recur in this population, as very few of these patients had no evidence of disease at their most recent follow-up. Our results are consistent with other studies that have demonstrated an increased risk of lower genital tract dysplasia in women after organ transplantation; however, only a few studies have assessed noncervical lower genital tract dysplasia among this high-risk population. Studies analyzing lower genital tract dysplasia among transplant recipients have demonstrated an increased incidence of dysplasia compared with the general population, however these studies were smaller, with the largest involving 262 patients. These studies demonstrated a prevalence of CIN between 3.3% and 49% in transplant recipients and typically simultaneously identified a few individuals who developed vulvar or vaginal dysplasia or carcinoma.14–24 Although these studies demonstrate an increased risk of dysplasia, their small and limited nature precludes conclusions regarding screening guidelines or a timeline in which these women are at highest risk. Our larger and more comprehensive assessment of all lower genital tract dysplasia is unique in this regard, and notably demonstrates that the prevalence of noncervical lower genital tract dysplasia is also increased (particularly given the lack of consistent screening beyond the cervix) when compared with the prevalence of cervical dysplasia. These findings are noteworthy because there are such limited data regarding noncervical lower genital tract dysplasia after solid organ transplantation.
In this analysis, we developed two multivariable models, the first including all significant explanatory variables to reduce confounding, as well as a limited multivariable analysis to improve power. In both models, black race and hydroxychloroquine use remained significantly associated with an increased risk of developing lower genital tract dysplasia. In the United States, black women are more likely to develop HPV-associated cancers than white women, including cervical and vaginal cancers.25 Black kidney transplant recipients are also more likely to suffer acute rejection and graft failure than white recipients; the proposed reasons for these disparities include socioeconomic factors, access to medical care, transplant wait times, differences in rates of hypertension and diabetes, differences in immunosuppressive regimens, differences in human leukocyte antigen, and differences in immune response to transplantation.26,27 The reasons underlying the increased risk of lower genital tract dysplasia associated with black race are likely multifactorial and related to other underlying health disparities. Further research in this area is needed to better understand and address this racial disparity. Hydroxychloroquine is most commonly used in kidney transplant recipients to treat lupus nephritis, and is recommended for all patients with lupus nephritis.28 Several studies have suggested that women with lupus may be at increased risk of developing cervical atypia and HPV infections.29,30 However, among transplant recipients with lupus nephritis, it is unclear to what extent immune dysfunction and specific immunosuppressive medications drive the development of dysplasia. One study evaluating the incidence of cervical cancer after renal transplant in patients with and without lupus found a similar incidence in these groups; however, they did not evaluate specific immunosuppressive medications or lupus severity.31 Further study in this area is warranted to better define this association between disease process, organ site, and immunosuppressive medications.
We found that the median time to develop CIN 2 or worse after first transplant was 3.95 years and 3.18 years after the most recent transplant; more than 70% of patients developed CIN 2 or worse in the first 5 years after their most recent transplant, and all developed CIN 2 or worse in the first 10 years after their most recent transplant. This is a shorter time frame than reported in previous studies. However, the U.S. Transplant Cancer Match Study found a median time of 3.8 years between transplant and invasive cervical cancers.12 Our findings suggest that a significant number of CIN 2 or worse diagnoses occur within 5 years after transplant, indicating that annual screening is a reasonable recommendation to detect these early cases of CIN 2 or worse. This more intensive screening appears to be important even in women who have had negative screening immediately before transplantation. Our HPV-specific data were limited in this analysis owing to minimal number of samples, and further research is needed to better understand the role of HPV testing in this setting and how this may affect the screening interval in this population.
We found the median time to develop VAIN 2 or worse, VIN 2 or worse, or AIN 2 or worse after the most recent transplant was 3.94 years and to noncervical lower genital tract cancer diagnosis was 3.63 years. The U.S. Transplant Cancer Match study similarly found a median interval between transplant and invasive cancer diagnosis was 4.1 and 5.3 years for vulvar and anal cancers respectively.12 Noncervical lower genital tract cancer was identified in 1.3% of the population and was more common than cervical cancer in this population. Although 12 of 13 (92%) of these patients had evidence of dysplasia at most recent follow-up, this may be a result of the fact that there is no universal screening for noncervical lower genital tract dysplasia in this population and biopsies often are performed only for suspicious lesions. Furthermore, although one of these cancers was identified after a finding of cervical dysplasia in the same patient, the majority of the noncervical lower genital tract cancers were identified independent of cervical disease, suggesting that recommendations focused only on cervical screening may miss a number of women who will develop other noncervical lower genital tract dysplasias or cancers. The higher rate of high-grade noncervical lower genital tract cancers may be partially due to the lack of screening for vulvar and vaginal dysplasia, because there is no routine screening test or recommendation currently. Although anal Pap tests were sometimes performed, they were not done routinely in this population. Given the frequency of noncervical dysplasia and invasive cancer in this population, complete lower genital tract evaluation in addition to cervical screening is warranted.
Our study has several limitations, including primarily that it was a retrospective design and conducted at a single institution. Therefore, there are limitations to the data available for analysis. In this regard, we cannot ensure that all posttransplant dysplasia was identified and therefore cannot report a true incidence of lower genital tract dysplasia. Additionally, only 79.7% of this population had a Pap test documented in our medical record after transplantation; thus, these findings may lead to an underestimation of the frequency of lower genital tract dysplasia, as women may have been diagnosed with dysplasia at an outside institution or had no screening at all, leading to undiagnosed cases. Finally, we also do not have access to every patient's complete gynecologic history before transplantation, leading to possible underreporting of the prevalence of abnormal screening before transplantation. Although this limitation makes it somewhat challenging to interpret whether the dysplasia identified were new diagnoses compared with progression of existing dysplasia, a history of abnormal screening was not associated with development of lower genital tract dysplasia on multivariate analysis.
Other limitations to our analysis include that we were unable to include specific analysis on patients who received the HPV vaccine owing to limited documentation of vaccination status in the medical record. As the HPV vaccine will continue to play an important role in prevention of HPV-associated dysplasia and cancers, further research is warranted to improve understanding of how vaccination may affect dysplasia incidence after transplantation. In addition, given the limited sample size of those who developed high-grade lower genital tract dysplasia, further analysis specific to this population was not feasible. A large, multi-institution study would be required to further explore this subset and to further understand the effect of HPV testing on this population as well. Despite these limitations, to our knowledge, this is the largest study that included all lower genital tract dysplasia, with the greatest number of patients who developed dysplasia after transplant.
As the number of living female transplant recipients grows annually, it is important for gynecologists to be mindful of this population's increased risk of dysplasia and screen them accordingly. Current cervical cancer screening guidelines from the American Society for Colposcopy and Cervical Pathology for the general population recommend cytology screening and high-risk HPV cotesting every 5 years for women ages 30–65 or, alternatively, cervical cytology screening every 3 years, and the U.S. Preventive Services Task Force also now gives the option of primary HPV testing.32,33 However, there is little evidence guiding cervical and lower genital tract cancer screening recommendations among women who have received a solid organ transplant. The American College of Obstetricians and Gynecologists recommends “more frequent” screening of these women, without a more specific recommendation.34 The most common recommendation for cervical screening in this population is annually, with many proponents of Pap tests with high-risk HPV cotesting.35,36 However, studies have demonstrated that despite recommendations for more frequent screening, uptake of the recommendation for yearly screening is low.36 Evidence-based best practice remains unclear, particularly with regards to noncervical dysplasia. Given the elevated rates of vaginal, vulvar, and anal dysplasia among this population, it is important for clinicians to screen these women with comprehensive lower genital tract exams, beyond just cervical Pap tests. In addition, owing to the high incidence of noncervical high-grade dysplasia and cancer, a lower threshold to perform anal cytology and biopsy suspicious lesions identified on exam may be warranted.
In conclusion, our findings suggest that at least 12% of transplant recipients may develop lower genital tract dysplasia after transplantation, of which about 50% may be high-grade, and 10% cancer. Our study suggests that yearly screening of transplant recipients, for at least the first 5–10 years after transplant, is reasonable to identify and treat women who develop dysplasia and cancer. Furthermore, screening for this population should not only include cervical screening, but should also include complete lower genital examination and anal Pap tests. Further prospective studies focused on all HPV associated lower genital tract disease are needed to further inform evidence-based guidelines for this high-risk population.
1. Transplants in the U.S. by recipient gender. Organ Procurement and Transplant Network data. Available at: https://optn.transplant.hrsa.gov/data/view-data-reports/national-data/#
. Retrieved March 14, 2019.
2. Chapman JR, Webster AC, Wong G. Cancer in the transplant recipient. Cold Spring Harb Perspect Med 2013;3:a015677.
3. Pietrzak B, Mazanowska N, Ekiel AM, Durlik M, Martirosian G, Wielgos M, et al. Prevalence of high-risk human papillomavirus cervical infection in female kidney graft recipients: an observational study. Virol J 2012;9:117.
4. de Sanjose S, Quint WG, Alemany L, Geraets DT, Klaustermeier JE, Lloveras B, et al. Human papillomavirus genotype attribution in invasive cervical cancer: a retrospective cross-sectional worldwide study. Lancet Oncol 2010;11:1048–56.
5. Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV, et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol 1999;189:12–9.
6. Smith JS, Backes DM, Hoots BE, Kurman RJ, Pimenta JM. Human papillomavirus type-distribution in vulvar and vaginal cancers and their associated precursors. Obstet Gynecol 2009;113:917–24.
7. De Vuyst H, Clifford GM, Nascimento MC, Madeleine MM, Franceschi S. Prevalence and type distribution of human papillomavirus in carcinoma and intraepithelial neoplasia of the vulva, vagina and anus: a meta-analysis. Int J Cancer 2009;124:1626–36.
8. Hoots BE, Palefsky JM, Pimenta JM, Smith JS. Human papillomavirus type distribution in anal cancer and anal intraepithelial lesions. Int J Cancer 2009;124:2375–83.
9. Demarco M, Lorey TS, Fetterman B, Cheun LC, Guido RS, Wentzensen N, et al. Risks of CIN2+, CIN3+, and cancer by cytology and human papillomavirus status: the foundation of risk-based cervical screening guidelines. J Low Genit Tract Dis 2018;21:261–7.
10. Judson PL, Habermann EB, Baxter NN, Durham SB, Virnig BA. Trends in the incidence of invasive and in situ vulvar carcinoma. Obstet Gynecol 2006;107:1018–22.
11. Johnson LG, Madeleine MM, Newcomer LM, Schwartz SM, Daling JR. Anal cancer incidence and survival: the surveillance, epidemiology, and end results experience, 1973-2000. Cancer 2004;101:281–8.
12. Madeleine MM, Finch JL, Lynch CF, Goodman MT, Engels EA. HPV-related cancers after solid organ transplantation in the US. Am J Transpl 2013;13:3202–9.
13. Grulich AE, van Leeuwen MT, Falster MO, Vajdic CM. Incidence of cancers in people with HIV/AIDS compared with immunosuppressed transplant recipients: a meta-analysis. Lancet 2007;370:59–67.
14. Meeuwis KAP, van Rossum MM, van de Kerkhof PCM, Hoitsma AJ, Massuger LFAG, de Hullu JA. Skin cancer and (pre)malignancies of the female genital tract in renal transplant recipients. Transplantation 2011;91:8–10.
15. Marschalek J, Helmy S, Schmidt A, Polterauer S, Sobulska M, Gyoeri GP, et al. Prevalence of genital dysplasia after kidney transplantation—a retrospective, non-interventional study from two centers. Acta Obstet Gynecol Scand 2015;94:891–7.
16. De Oliveria Martins CA, Guimaraes ICCDV, Velarde LGC. Relationship between the risk factors for human papillomavirus infection and lower genital tract precursor lesion and cancer development in female transplant recipients. Transpl Infect Dis 2017;19:e12714.
17. 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.
18. Paternoster DM, Cester M, Resent C, Pascoli I, Nanhorngue K, Marchini F, et al. Human papilloma virus infection and cervical intraepithelial neoplasia in transplanted patients. Transplant Proc 2008;40:1877–80.
19. Haar-Van Eck SAT, Rischen-Vos J, Chada-Ajwani S, Huikeshoven FJM. The incidence of cervical intraepithelial neoplasia among women with renal transplant in relation to cyclosporine. Br J Obstet Gynecol 1995;102:58–61.
20. Alloub MI, Barr BBB, McLaren KM, Smith IW, Bunney MH, Smart GE. Human papillomavirus infection and cervical intraepithelial neoplasia in women with renal allografts. BMJ 1989;298:153–6.
21. Silverberg MJ, Leyden WA, Chi A, Gregorich S, Huchko MJ, Kulasingam S, et al. Human immunodeficiency virus (HIV)– and non-HIV–associated immunosuppression and risk of cervical neoplasia. Obstet Gynecol 2008;0:1–9.
22. Ogunbiyi OA, Scholefield JH, Raftery AT, Smith JH, Duffy S, Sharp F, et al. Prevalence of anal human papillomavirus infection and intraepithelial neoplasia in renal allograft recipients. Br J Surg 1994;81:365–7.
23. Ghazizadeh S, Lessan-Pezeshki M, Einollahi B, Khatami MR, Makhdoomi K. Uterine cervical intraepithelial neoplasia in renal transplantation. Transplant Proc 2001;33:2817.
24. Mazanowska N, Pietrzak B, Kamiński P, Ekiel A, Martirosian G, Jabiry-Zieniewicz Z, et al. Prevalence of cervical high-risk human papillomavirus infections in kidney graft recipients. Ann Transpl 2013;18:656–60.
25. HPV-associated cancer rates by race and ethnicity. Available at: https://www.cdc.gov/cancer/hpv/statistics/race.htm
. Retrieved October 25, 2018.
26. Isaacs RB, Nock SL, Spencer CE, Connors AF, Wang XQ, Sawyer R, et al. Racial disparities in renal transplant outcomes. Am J Kidney Dis 1999;34:706–12.
27. Eckhoff DE, Young CJ, Gaston RS, Fineman SW, Deierhoi MH, Foushee MT, et al. Racial disparities in renal allograft survival: a public health issue? J Am Coll Surg 2007;204:894–902.
28. Bertsias GK, Tektonidou M, Amoura Z, Aringer M, Bajema I, Berden JH, et al. Joint European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of adult and paediatric lupus nephritis. Ann Rheum Dis 2012;71:1771–82.
29. Al-Sherbeni HH, Fahmy AM, Sherif N. Predisposition to cervical atypia in systemic lupus Erythematous: a clinical and cytopathological study. Autoimmune Dis 2015;2015:751853.
30. Nath R, Mant C, Luxton J, Hughes G, Raju KS, Shepherd P, et al. High risk of human papillomavirus type 16 infections and of development of cervical squamous intraepithelial lesions in systemic lupus erythematosus patients. Arthritis Care Res 2007;57:619–25.
31. Ramsey-Goldman R, Brar A, Richardson C, Salifu MO, Clarke A, Bernatsky S, et al. Standardized incidence ratios (SIRs) for cancer after renal transplants in systemic lupus erythematosus (SLE) and non-SLE recipients. Lupus Sci Med 2016;3:e000156.
32. Massad LS, Einstein MH, Huh WK, Katki HA, Kinney WK, Schiffman M, et al. 2012 updated consensus guidelines for the management of abnormal cervical cancer screening tests and cancer precursors. Obstet Gynecol 2013;121:829–46.
33. US Preventive Services Task Force, Curry SJ, Curry SJ, Krist AH, Owens DK, Barry MJ, Caughey AB, et al. Screening for cervical cancer: US Preventive Services Task Force recommendation statement. JAMA 2018;320:674–86.
34. Cervical cancer screening and prevention. Practice Bulletin No. 168. American College of Obstetricians and Gynecologists. Obstet Gynecol 2016;128:e111–30.
35. Veroux M, Corona D, Scalia G, Garozzo V, Gagliano M, Giuffrida G, et al. Surveillance of human papilloma virus infection and cervical cancer in kidney transplant recipients: preliminary data. Transpl Proc 2009;41:1191–4.
36. Courtney AE, Leonard N, O'Neill CJ, McNamee PT, Maxweell AP. The Uptake of cervical cancer screening by renal transplant recipients. NDT 2009;24:647–52.