There is a historical low uptake of both cervical screening and HPV vaccination in this cohort.
The authors conducted two surveys of kidney transplant recipients to identify current adherence with cervical screening recommendations and the prevalence rate of HPV vaccination in an Irish cohort.
While many kidney transplant recipients were aware of their increased cancer risk, they were mostly unaware of the potential benefits of HPV vaccination in reducing cancer risk and that HPV vaccination is guideline recommended.
In 2021, the recommendation reverted to annual cervical screening for post-transplant recipients, even those with a negative HPV result.
A cut-off age of 65 years was used for cervical screening in line with Irish cervical screening guidelines.
Key Points
1. Kidney transplant recipients are at a higher risk of human papillomavirus (HPV)-related cancers than the general population. There is a historical low uptake of both cervical screening and HPV vaccination in this cohort.
2. The authors conducted two surveys of kidney transplant recipients to identify current adherence with cervical screening recommendations and the prevalence rate of HPV vaccination in an Irish cohort.
3. Cervical screening adherence was higher than previously reported, but a risk of bias exists. HPV vaccination rates were low. While many kidney transplant recipients were aware of their increased cancer risk, they were mostly unaware of the potential benefits of HPV vaccination in reducing cancer risk and that HPV vaccination is guideline recommended.
INTRODUCTION
Kidney transplant recipients (KTR) face a higher risk of developing cancer than the general population due to immunosuppression therapy.1 Cervical cancer is the fourth most common cancer in women worldwide, accounting for 6% of all female cancers, but occurs with a higher incidence rate in KTRs compared to the general population, at 9.6 and 6.6 cases per 10,000 patient-years, respectively.2,3 The incidence rate of cervical cancer in renal transplant patients is higher in both younger patients and those with a longer duration of immunosuppression therapy.4 Human papillomavirus (HPV) is the main aetiological factor in cervical cancer, and persistent HPV infection in the setting of immunosuppression is a significant risk factor for the development of cervical intraepithelial neoplasia (CIN) and cervical cancer in KTRs.5-8 Use of high-dose corticosteroids, in particular, increases the risk of HPV infection and persistence.9 Other risk factors for cervical cancer in renal transplant patients include older age at transplantation, high dose steroid use, smoking, and a history of CIN or cervical cancer before transplantation.9,10
Prevention strategies for cervical cancer in renal transplant patients include vaccination against HPV, cessation of smoking, and regular screening for CIN and cervical cancer. Guidelines recommend HPV vaccination for all renal transplant patients before transplantation, or as soon as possible after transplantation in both male and female patients aged <45 years, with the HPV9 vaccine currently recommended in Irish guidelines.11,12 However, the efficacy of the vaccine may be reduced in immunosuppressed patients, and the optimal timing and dosing of the vaccine in this population are still unclear.13 To the authors’ knowledge, no data are currently available regarding the uptake of this vaccine in KTRs in Ireland. Internationally, a low HPV vaccination rate is reported in some small studies of KTRs, varying from 4–32%, with a lack of awareness regarding the importance of vaccination commonly identified.14,15
Regular screening for CIN and cervical cancer is essential for the early detection and treatment in KTRs. Historical international guidelines recommended annual cervical cytology screening for female renal transplant patients.16-18 The Irish cervical screening programme, which moved from Pap smear cytology screening to HPV testing in March 2020, currently recommends screening take place within 1 year of kidney transplantation and then on an annual basis thereafter for patients with a negative HPV test between the ages of 25–65 years old.19 This annual HPV screening recommendation in Ireland had changed in the 2020 screening eligibility guidelines (Version 8), recommending that KTRs with a negative HPV test should undergo the standard HPV screening algorithm (i.e., screening every 3 years for ages 25–29 years and every 5 years for ages ≥30 years for patients with a negative HPV test). In 2021, the recommendation reverted to annual cervical screening for post-transplant recipients, even those with a negative HPV result. Little is known about the uptake of cervical screening in Irish KTRs in the current era. Previous studies, conducted prior to a well-established national cervical screening programme, suggested that uptake of screening in this region was very low.20,21
AIMS
In this study, the author sought to identify adherence with cervical screening and the prevalence rate of HPV vaccination in KTRs, and also to identify what patient-level barriers may exist to improving adherence with recommendations.
METHODS
Study Design, Setting, and Participants
A retrospective cohort study was conducted in a single centre to target two groups: firstly, all female KTRs ≤65 years regarding cervical screening, and secondly, all KTRs ≤45 years regarding HPV vaccination status. A cut-off age of 65 years was used for cervical screening in line with Irish cervical screening guidelines. Patients with a prior hysterectomy were excluded. A cut-off age of 45 years was used for the HPV vaccination group, as Irish vaccination guidelines recommend all KTRs ≤45 years should receive the HPV9 vaccine.
Data Collection and Analysis
Telephone consultations were conducted by junior doctors, unknown to the KTRs, to ascertain patient adherence with cervical screening, knowledge of screening recommendations, self-reported occurrence of an abnormal screening test, HPV vaccination status, and any patient-perceived barriers in adhering to recommended practice. KTRs of less than 12 months vintage or prior hysterectomy were excluded from the female patient ≤65 years cohort. No previously validated questionnaires were available to the research team for these purposes. Data collection took place from June–October 2022. Descriptive statistics, including cohort means, SD, and percentages were utilised to summarise the study results.
Ethical Approval
Ethical approval was granted by the local Research Ethics Committee. Informed consent was obtained from all participants.
RESULTS
Cervical Screening Survey
From a total cohort of 337 KTRs in the authors’ centre, there were 217 female KTRs ≤65 years old. Of these, 42 patients agreed to participate and three were excluded for a previous hysterectomy. Of the 39 included patients, the mean age was 45.3 years (SD: 10; median age: 44 years; SD: 10.6) and the mean transplant vintage was 123.6 months (SD: 86.2). The responses to the survey are summarised in Table 1. Since the time of transplantation, 34 patients (87%) had undergone a cervical screening and all of these patients reported attending screening whenever reminded or invited to do so by the cervical screening programme. There were five patients (13%) who had not attended cervical screening since the time of transplantation, and two of those indicated that the reason was that they had not received any communication from the cervical screening programme. Awareness of a specific recommendation for annual cervical screening in post-transplant recipients was evident in 27 patients (69%). Abnormal cervical screening had been detected in 18 patients (46%) and all of those had undergone colposcopy and large loop excision of the transformation zone procedure. A diagnosis of CIN was reported by six patients (15%). No patient had received a diagnosis of a gynaecological cancer since transplantation.
