Increased Risk of Cervical Dysplasia in Long-Term Survivors of Allogeneic Stem Cell Transplantation—Implications for Screening and HPV Vaccination

Abstract

As more women survive allogeneic stem cell transplantation (SCT), the development of genital human papilloma virus (HPV)-related squamous intraepithelial lesions (SIL) warrants study. Thirty-five of 38 females followed prospectively long-term after SCT for hematological malignancies (median: 7 years posttransplant) were adults and had cervical cytology testing. Acute graft-versus-host-disease (aGVHD) occurred in 9 and chronic (cGVHD) in 34 patients. Six (17%) continued receiving systemic immunosuppressive therapy (IST) for cGVHD >3 years after SCT. Of 15 (43%) with abnormal cytology, 12 (34%) patients had HPV-related SIL (median time to SIL 51 months, range: 22-108) including high-grade SIL in 7 (20%). Patients requiring continued IST had the highest risk (odds ratio [OR] 4.6, 95% confidence interval [CI] 1.1-16.4; P = .019). This high incidence of SIL in long-term SCT survivors underscores the importance of gynecologic assessment after transplantation, especially in those requiring IST. This may portend an increased risk of genital or other HPV-related malignancies.

Comparison of graft-versus-host disease-free, relapse-free survival according to a variety of graft sources: antithymocyte globulin and single cord blood provide favorable outcomes in some subgroups

“…Previous studies found that chronic GvHD was a major factor associated with risk of secondary solid cancer. [19][20][21][22] Although the absence of significant GvHD may not be a long-term goal, particularly for patients with high-risk disease, the relationship among graft sources remained similar even in the weighted analyses. These results favor the use of bone marrow graft for sibling HCT to promote ideal recovery of patients without significant morbidity in the Japanese population.…”

Clinical guidelines for gynecologic care after hematopoietic SCT. Report from the international consensus project on clinical practice in chronic GVHD

“…24,41 Prolonged use of immunosuppressive drugs to treat cGVHD and severity of cGVHD are major risk factors for the development of human papillomavirus (HPV)-related dysplasia 15 and squamous cell carcinoma of the female genital tract. 42 We recommend performing regular gynecological examination including cervical cytology once a year 15,16 (BIIa). In the case of suspicious genital lesions, colposcopy and biopsy are recommended (BIIa).…”

“…If the treatment is not successful in a timely manner (6-8 weeks), we perform a biopsy of the lesions to exclude malignancies 15 (AIIa). around the periclitoral hood accompanied by the typical porcelain-white lesions that are easily distinguishable from genital cGVHD.…”

“…Secondary malignancies of the female genital tract Regular gynecological examination including cervical cytology should be performed once a year 15,16 BIIa If treatment of suspected genital cGVHD is not successful in a timely manner (6-8 weeks), biopsy of the lesion should be performed to avoid incorrect diagnosis, erroneous treatment and exclude malignancies 15,17 AIIa Biopsy is recommended for all genital lesions suspicious for dysplasia or malignancy 15 BIIa HPV vaccination may be offered to young women (12-26 years) after transplantation 18 …”

Impfungen bei Immundefekten/Immunsuppression – Expertenstatement und Empfehlungen

“…einem Drittel der Langzeit-Überlebenden auftritt. Ebenso stellt eine länger andauernde immunsuppressive Therapie aufgrund einer chronischen GvHD ein erhöhtes Risiko für die Entwicklung HPV-induzierter squamöser intraepithelialer Läsionen dar [76,77]. Die Impfung kann jedoch für diese Patienten in Erwägung gezogen werden und ein regelmäßiges HPV-Screening S362 Impfungen bei Immundefekten/Immunsuppression -Expertenstatement und Empfehlungen K consensus report wird speziell empfohlen (Kostenübernahme durch Sozialversicherungsträger zur Zeit nicht geklärt).…”