Risks factors and timing of genital human papillomavirus (HPV) infection in female stem cell transplant survivors: a longitudinal study

Abstract

This longitudinal single-center study describes the timing and risk factors for genital human papillomavirus (HPV) disease in women after allogeneic hematopoietic cell transplantation (HCT). Between 1994 and 2014, 109 females underwent HCT of whom 82 surviving transplant for >1 year had regular, comprehensive genital tract assessment and treatment of HPV disease. The cumulative proportions of any genital HPV infection at 1, 3, 5, 10 and 20 years were 4.8%, 14.9%, 28.1%, 36.7% and 40.9%, respectively. Demographic, disease-related factors, chronic GvHD (cGvHD) and its treatment were analyzed for their association with persistent, multifocal or severe genital HPV disease. Pre-transplant HPV disease was strongly associated with any posttransplant HPV (odds ratio (OR)=6.5, 95% confidence interval (CI)=1.65-25.85, P=0.008). Having either extensive or genital cGvHD was associated with increased risk of any HPV disease (OR=5.7, 95% CI=1.90-17.16, P=0.002) and a higher risk for severe genital dysplasia (CIN II-III/VIN II-III; OR=13.1, 95% CI=1.59-108.26, P=0.017), but no one developed HPV-related genital cancer. Persistent, multifocal or severe HPV disease occurred more frequently than in healthy populations. Women with extensive cGvHD, genital cGvHD or pre-transplant HPV are at greatest risk for post-transplant HPV disease. Early initiation of annual screening, comprehensive genital tract assessment and active management are cornerstones of their gynecology care.

A Practical Guide to Gynecologic and Reproductive Health in Women Undergoing Hematopoietic Stem Cell Transplant

“…HPV, a common STI, causes cervical cancer, and in particular, HPV16 and HPV18 cause over 70% of cases [57]. Before transplant, immunocompromised patients are at risk of latent HPV reactivation and new HPV infection [58,59]. The pretransplant evaluation for those who have been sexually active, regardless of age, includes reviewing prior cervical cytology and HPV testing along with treatment history, as well as obtaining a pretransplant cervical cytology and HPV test.…”

“…Topical estrogens can increase epithelial thickness of thin, treated mucosa [2]. Genital cGVHD and its treatment may be associated with HPV reactivation [58,59]. Assessment of HPV lesions and cervical cancer screening are included in the lower genital tract examination.…”

“…After transplant, immunocompromised patients are at risk of new HPV infection and latent HPV reactivation, and they may experience more rapid progression to premalignant and malignant neoplastic lesions than the general population Adapted from Li et al [3]. [6,59,75,77]. About 40% of females have an abnormal cervical cytology after HCT, with 20% having high-grade cervical or lower genital tract SIL warranting treatment [59].…”

“…[6,59,75,77]. About 40% of females have an abnormal cervical cytology after HCT, with 20% having high-grade cervical or lower genital tract SIL warranting treatment [59]. Thus, both cervical and vulvar precancerous lesions are potentially more common in those with cGVHD and pose an increased genital squamous cell cancer (cervical or vulvar) risk compared with the general population [1,6,77].…”

“…Performing an excisional biopsy excludes high-grade SIL or cancer and alleviates concerns of rapid progression during transplant-related immunodeficiency or while taking immunosuppressive or immunomodulating agents. As HPV disease can occur anywhere in the lower genital tract, the examination includes inspection and assessment of the vulva, vagina, and entire anogenital region, in addition to cervical cancer screening [1,59]. Current consensus for post-HCT care recommends annual pelvic examination with cervical cytology and HPV DNA cotesting for all HCT patients annually following transplant [75,78].…”