Between November 2019 and July 2021, 201 women were enrolled in the study. These included 98 kidney transplant recipients, 93 liver transplant recipients, and ten patients who received simultaneous kidney and liver transplantation. 65.2% of patients knew they were at increased risk for genitoanal cancers, and 77.6% knew cervical screening could reduce cancer risk. In addition, most patients (92.5%) reported regularly taking advantage of the cervical screening offer.
HrHPV prevalence
The baseline characteristics of the participants are shown in Table 1, which compares hrHPV positive and negative patients. Overall, 32 out of 201 (15.9%) patients tested positive for hrHPV at the cervical site. The anal hrHPV prevalence was 20.3% (40/197). No significant difference in cervical hrHPV prevalence was found between kidney and liver transplanted patients (see Table 2). The median age was 52 years (median 18–78), with cervical hrHPV-positive patients being, on average, eight years younger (p = 0.029). HrHPV prevalence declined with increasing age as shown in Fig. 1. However, the differences in cervical hrHPV prevalence across age groups were not statistically significant (p = 0.068), whereas anal hrHPV prevalence did show a significant difference across age groups (p = 0.038). When comparing individuals aged ≤ 45 years to those > 45 years, anal hrHPV prevalence was significantly higher in the younger age group (p = 0.020). In contrast, cervical hrHPV prevalence showed a non-significant trend towards higher rates in the younger group (p = 0.078).The median body mass index (BMI) was 23.4 in the cervical hrHPV-negative group and 21.4 in the cervical hrHPV-positive group (p = 0.030).
hrHPV = high-risk human papillomavirus
Immunosuppressive treatment
Overall, 97.5% of the patients were currently taking immunosuppressants, with most (75%) being on a calcineurin inhibitor (CNI) based immunosuppressive regimen consisting of more than two drugs. A comparison of immunosuppression and HPV risk factors is shown in Table 1. Neither the number of immunosuppressants nor the type of immunosuppression was significantly associated with hrHPV infection. Other transplant-specific variables, such as duration of immunosuppressive treatment, pretransplant immunosuppressant use, or graft rejections, did not correlate with hrHPV infection. A comparison of kidney and liver transplant recipients showed differences in immunosuppressive therapy (see Table 2). Compared to liver transplants, more kidney recipients took at least two immunosuppressants and had higher induction therapy rates (85.5% vs. 37%). However, cervical hrHPV prevalence showed no significant difference. Additionally, risk factors like sexual partners and age at first intercourse didn’t differ between kidney and liver recipients.
Risk factors associated with increased HPV prevalence in the general population, i.e. sexual behaviour and younger age, are confirmed in transplanted patients in a multivariable logistic regression model, with adjusting for transplantation, nicotine use and age of first intercourse (see Table 3). HrHPV-positive women were, on average, one year younger at the time of first sexual intercourse (p = 0.025) and had more than twice as many sexual partners as HPV- negative patients (p < 0.001). Likewise, the number of sexual partners since the first transplant was significantly higher among hrHPV-positive patients (p < 0.001).
HPV vaccination
In total, 12.4% (25/201) of patients had prior HPV vaccination. Among them, 80% (20/25) were under 30, while only 2.9% (5/173) of those over 30 were vaccinated (p < 0.0001). Most patients were vaccinated before their first sexual intercourse (17/25), and six were vaccinated before transplantation. The number of vaccinated patients was higher among HPV-positive patients compared with HPV-negative patients (see Table 1). Three HPV-positive women were vaccinated after their first sexual intercourse and six after their transplantation.
Follow-up
The participation rate in the follow-up offered 6 to 18 months after the initial HPV test for cervical hr-HPV positive patients was 91%, with 29 out of 32 patients returning. The positive hr-HPV result was confirmed in 25 cases. In 52% (13/25), more than one HPV type was determined by genotyping. A total of 14 different HPV-Types with oncogenic potential were detected in the cervical site (HPV 16, 18, 31, 33, 39, 45, 51, 52, 56, 58, 59, 66, 68, 73). High-grade squamous intraepithelial lesion (HSIL) was detected in four patients during follow-up in the dysplasia unit (1x CIN2, 2x CIN3, 1x VaIN3). Three out of four patients with precancerous lesions had normal pap smears (NILM).
In anal swab specimens more than one HPV genotype was detected in 52.5% of patients, and 11 different high-risk oncogenic genotypes were identified (HPV 16, 18, 31, 39, 45, 51, 52, 56, 58, 59, 68). The most common HPV-types are shown in Fig. 2.
* This refers to the number of tested patients; multiple HPV types can occur in a single patient. HPV = Human papillomavirus
Anal and cervical co-infection
For further investigation of co-infection in cervical hrHPV-positive patients, genotyping was performed at follow-up, whereas anal HPV testing involved genotyping at baseline and follow-up, and one positive test was considered sufficient for hrHPV positivity. All detected HPV types were included in the evaluation of co-infection, regardless of the time of examination. In patients with cervical hrHPV positivity, anal co-infection was detected in 68,8% (22/32), whereas in cervical HPV-negative patients, only 10.9% (18/165) had an anal hrHPV infection. In 18 of 23 patients, cervical and anal genotyping was available to compare HPV genotypes. Fifteen of these 18 patients were positive for more than one HPV type. There was a strong association at the HPV-specific level: 78% (14/18) of patients exhibited at least one concordant hrHPV type, while 22% (4/18) displayed different hrHPV genotypes. The highest concordance rate was found for HPV 16, with all 6 out of 6 patients (100%) showing a coinfection in the anal swab specimens.