Objective Worldwide, transgender women are an at-risk population for contracting sexually transmitted infections. Little information exists on symptoms and characteristics of neovaginal human papillomavirus (HPV) infections and associated diseases. We describe a case series of transgender women with symptomatic HPV-related neovaginal lesions and a review of current literature.
Methods Transgender women with symptomatic HPV-related neovaginal lesions were identified from a departmental database comprising clinical and outpatient data on transgender women who underwent vaginoplasty between 1990 and 2015. HPV status was determined on excision and biopsy specimens by HPV DNA testing using GP5+6+-PCR and p16INK4A immunohistochemistry. Current literature was reviewed using the MEDLINE and EMBASE databases.
Results This case series includes four transgender women with symptomatic, HPV-related neovaginal lesions. Two women presented with neovaginal and neovulvar pain and condylomata/leukoplakia, which were excised. These lesions showed moderate-to-severe dysplasia at histopathological examination, and were positive for high-risk HPV (hrHPV) and p16INK4A. Recurrence occurred in one patient and was treated with laser evaporation. Two women presented with neovaginal coital pain, neovaginal bleeding and condylomata. Neovulvar lesions were treated with podophyllotoxin. Neovaginal lesions were excised or evaporated. These lesions were low-risk HPV (lrHPV) positive. The literature search shows treatment options varying from conservative, topical podophyllotoxin to excision or laser evaporation under general anaesthesia.
Conclusions Neovaginal HPV infection can lead to benign condylomata (lrHPV) and various grades of dysplasia (hrHPV). We advise physicians to consider HPV infection and associated lesions in transgender women with otherwise unexplainable neovaginal pain or bleeding after vaginoplasty.
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In vaginoplasty, a vagina is surgically created. It is indicated for transgender women and biological women with congenital or acquired absence of the vagina. Multiple surgical techniques can be employed for this procedure. In transgender women, penile skin inversion vaginoplasty is performed most commonly. Other types of graft used for this procedure include intestinal segments, full or split skin grafts and pedicled fasciocutaneous flaps. Patients who undergo vaginal (re)construction are able to engage in sexual relationships and are therefore susceptible to acquisition of neovaginal HPV infection and other sexually transmitted infections (STIs). Sexually inactive transgender women can also be infected, because of the possibility of preoperative asymptomatic penile HPV infection and non-sexual transmission. Worldwide, transgender women are regarded as an at-risk population for HIV infection and STIs. Little information exists on the symptoms and characteristics of HPV-associated lesions in transgender women who underwent vaginoplasty. We describe a case series and review of literature of transgender women with symptomatic HPV-related lesions of the neovagina.
Transgender women with symptomatic HPV-related neovaginal lesions were identified from a departmental database of 1082 transgender women who underwent vaginoplasty at our institution. This database was created by the first author through a retrospective chart review of all transgender women who underwent vaginoplasty between 1990 and 2015, recording intraoperative and postoperative surgical complications, reoperations and postoperative aberrancies at outpatient follow-up visits. Patients with neovaginal lesions that tested positive for HPV were included. Demographics, type of vaginoplasty procedure, HPV-associated symptoms and treatment type and results were recorded. Written approval was obtained from the institutional Medical Ethical Exam Committee from the VU University Medical Center (2012/157).
Excision or biopsy specimens were used for histological analysis, p16INK4a immunostaining and DNA isolation. DNA isolates were subjected to GP5+/6+ PCR with an enzyme immunoassay read-out using a probe cocktail of 14 high-risk HPV types (ie, HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68) and 23 low-risk HPV types (ie, HPV 6, 11, 26, 34, 40, 42, 43, 44, 53, 54, 55, 57, 61, 70, 71, 72, 73, 81, 82/mm4, 82/is39, 83, 84 and cp6108). HrHPV genotyping was performed using Luminex suspension array technology and lrHPV genotyping by the reverse line blot assay.
A literature search was conducted using the electronic, scientific database MEDLINE (Pubmed) and EMBASE. The electronic search strategy included both Medical Subject Headings (MeSH) and keywords, using the search string: (‘Papillomaviridae’[MeSH terms] OR ‘Condylomata acuminata’[MeSH terms] OR ‘HPV’[All fields] OR ‘human papillomavirus’[All fields]) AND (‘Transgendered Person’ [MeSH terms] OR ‘Sex Reassignment Procedures’[MeSH terms] OR ‘Transgender’[All fields] OR ‘Transsexual’[All fields] OR ‘Neovagina’[All fields] OR ‘Vaginoplasty’[All fields] OR ‘Neocolporrhaphy’[All fields] OR ‘Vaginal reconstruction’[All fields]). Studies published between January 1970 and October 2015 were included. Title and abstract of all retrieved studies were screened. Studies that did not report HPV-related symptomatic lesions in transgender women were omitted.
A 41-year-old transgender woman consulted our outpatient clinic with neovaginal coital pain and self-noticed neovaginal warts. She underwent penile inversion 20 years before presentation and had been sexually active with multiple men in the previous year. She did not engage in penetrative anal intercourse. HIV blood tests were negative. At physical examination, multiple introital condylomata were observed. Thorough neovaginal examination was not possible, because of patients’ severe anxiety. We decided to perform neovaginal examination, and possibly treatment, under general anaesthesia. In speculo, multiple neovaginal as well as introital and perineal condylomata were observed, which were excised without complications. At histopathological examination, severe dysplasia of the squamous epithelium was observed (see online supplementary figure S1). Presence of hrHPV, type 16, was confirmed and the lesions stained immunopositive for p16INK4A, a biomarker for a transforming hrHPV infection. At 8-month follow-up, there was recurrence of symptoms and condylomata, for which carbon dioxide laser vaporisation was performed. No HPV subtyping was performed at this stage. No recurrence was reported after this with 6 months of follow-up.
A 37-year-old transgender woman consulted our outpatient clinic with symptoms of neovulvar pain. She underwent penile inversion vaginoplasty 15 years before presentation and had been sexually active with men until the age of 32. She did not engage in penetrative anal intercourse. HIV blood tests were negative. At physical examination, introital leukoplakia was observed of which three biopsy specimens were obtained. Moderate dysplasia of the squamous epithelium was observed during histopathological examination. The neovaginal lesions were excised under general anaesthesia. At histopathological examination of the excised tissue, severe dysplasia of the squamous epithelium was observed (see online supplementary figure S2). Presence of hrHPV type 33 was confirmed and the lesion was p16INK4A immunopositive. After surgery, her symptoms resolved and at 3-year follow-up, there was no recurrence of neovaginal lesions.
A 28-year-old transgender woman consulted our outpatient clinic with neovaginal pain during coitus and dilatation. She underwent penile inversion vaginoplasty 7 years before presentation and was sexually active with men. She did not engage in penetrative anal intercourse. HIV and hepatitis blood tests were negative. At physical examination, multiple neovulvar and three neovaginal condylomata were observed. The neovulvar lesions were successfully treated with podophyllotoxin cream (0.15%). After a biopsy specimen was obtained, all neovaginal lesions were treated with laser vaporisation under general anaesthesia. There were no complications. Presence of lrHPV DNA was confirmed, but insufficient material was left for genotyping. At histopathological examination, a hyperkeratotic papilloma with acanthosis and koilocytosis was observed, consistent with condylomata acuminatum. At 2-year follow-up, there was no recurrence of neovaginal condylomata.
A 47-year-old transgender woman consulted our outpatient clinic with neovaginal pain and bleeding, most noteworthy after urination and defecation. She underwent penile inversion vaginoplasty 9 years before presentation and anamnestically had engaged only once in penetrative sexual intercourse with a man. She did not engage in penetrative anal intercourse. At physical examination, seven condylomata acuminata, measuring 0.5–1.5 cm, were observed at the external urethral meatus, neovulva and neovagina. These were all excised without intraoperative complications under general anaesthesia. At histopathological examination of the excision specimen, a condylomatous architecture and cytonuclear polymorphism, acanthosis and koilocytosis were observed (see online supplementary figure S3). Presence of lrHPV DNA, type 11, was confirmed. HIV and hepatitis blood tests were negative. At 3-year follow-up, there was no recurrence of neovaginal condylomata.
With the literature search, 30 references were identified. After screening of these 30 studies on title abstract and full text, nine were included in our literature review that reported on symptomatic neovaginal HPV lesions in transgender women (table 1). All studies included were small case series or case reports and reported on few patients. HPV typing was performed on three patients. A wide range of treatment modalities were reported, ranging from topical treatment (trichloroacetic acid, podophyllin or imiquinod) to laser evaporation, excision and even total colpectomy.
In this case series, we report on four transgender women with symptomatic HPV-related neovaginal lesions. All patients experienced neovaginal pain. Multiple factors can cause neovaginal pain after vaginoplasty, for example, postoperative pain, overactive pelvic floor muscles, excessive neovaginal dilatation and STIs. Neovaginal and introital pain in the first postoperative year is frequently caused by scarring and is considered a normal occurrence. We advise physicians to consider an HPV-associated lesion in patients with otherwise unexplainable neovaginal pain or bleeding after vaginoplasty, especially in sexually active patients who underwent vaginoplasty longer ago.
Different types of graft are used for vaginoplasty both in biological and transgender women. In transgender women, HPV-related lesions have been described in split-thickness skin graft and penile inverted skin flap neovaginas.1–9 Which of these grafts is more susceptible for HPV infection is unknown. There is no guideline which addresses management of HPV-related neovaginal lesions, and a wide range of treatment modalities are reported. Follow-up of hrHPV-infected transgender women seems advisable. The four patients described were identified from a departmental database of 1082 transgender women who underwent vaginoplasty at our institution. We may not have reported all HPV-related neovaginal lesions in our transgender population, because patients might not have contacted a healthcare professional with (minor) symptoms.
Extensive HPV prevalence studies have not been performed in transgender women in Europe. In a recent study, Loverro et al10 reported on HPV prevalence in transgendered persons in Italy, in which one out of a total of eight women who underwent vaginoplasty tested positive for vaginal hrHPV. However, the number of included patients in this study is small, so the true clinical importance and burden of neovaginal HPV infections in transgender women in Europe remains unclear.
To conclude, transgender women can develop neovaginal HPV-positive benign condylomata (lrHPV) and various grades of dysplasia (hrHPV) after vaginoplasty. Symptoms may include neovaginal pain and bleeding. Previously only 11 cases on symptomatic HPV-related neovaginal lesions were reported, we add four cases that were completely evaluated including histopathology and HPV typing. Follow-up of HPV-infected transgender women seems advisable. We advise physicians to provide sexual education, especially regarding preventive measures, and to consider an HPV infection and associated lesions in patients with otherwise unexplainable neovaginal pain or bleeding after vaginoplasty.
Abstract in Dutch
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- Abstract in Dutch - Online abstract
Handling editor Jackie A Cassell
Contributors WBvdS, MEBu and MGM designed the study. All authors contributed to acquisition, analysis or interpretation of data for the work. WBvdS wrote the first draft. All authors contributed to successive drafts and reviewed the final manuscript.
Competing interests None declared.
Ethics approval Medical Ethical Exam Committee (METC) VU University Medical Center.
Provenance and peer review Not commissioned; externally peer reviewed.