Cancer risk and screening in transgender and gender-diverse individuals on gender-affirming hormone therapy: a review article for the Australasian context

The healthcare landscape for transgender and gender-diverse (TGD) individuals in Australasia has evolved significantly, with general practitioners increasingly recognised as essential providers of comprehensive care for this community.¹ Gender-affirming hormone therapy (GAHT) represents a cornerstone of medical transition, involving the administration of cross-sex hormones to align physical characteristics with gender identity. For transfeminine individuals, this typically includes oestrogen and anti-androgen therapy, while transmasculine individuals receive testosterone therapy.²

As access to GAHT expands across Australasia, understanding the long-term health implications becomes increasingly important for general practitioners. Cancer risk represents a particular area of clinical concern, given the known influence of sex hormones on carcinogenesis in various tissues.³ The skin, as a hormone-responsive organ, undergoes significant changes during GAHT, including alterations in texture, sebaceous gland activity, hair growth patterns and cellular behaviour.⁴

Epidemiological data in cisgender populations demonstrate clear sex-dependent differences in cancer incidence, suggesting important roles for endogenous sex hormones in cancer development.⁵ However, the impact of exogenous cross-sex hormones administered during GAHT on cancer risk in transgender individuals remains an evolving area of research.² This uncertainty creates challenges for general practitioners in providing evidence-based advice on cancer screening and prevention strategies.⁶

This review article aims to synthesise the current evidence on cancer risk associated with GAHT and to provide practical, evidence-based screening recommendations for general practitioners in Australia and New Zealand. In addition to addressing cancer risk, this review acknowledges the important role of primary care providers in counselling patients about the potential long-term health implications of GAHT and gender-affirming surgery before treatment initiation as part of a comprehensive informed consent process.

Methods

This article review was conducted and reported in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 statement. The PRISMA 2020 flow diagram is presented as Figure 2.

Search strategy

A comprehensive literature search was performed to identify relevant epidemiological studies, case reports, clinical guidelines and systematic reviews published up to March 2026. The search was conducted across multiple electronic databases, including PubMed/MEDLINE, Embase, Scopus and the Cochrane Library. The search strategy combined keywords and medical subject headings (MeSH) terms related to TGD populations, GAHT and cancer. The principal search terms included: “transgender”, “transsexual”, “gender diverse”, “gender-affirming hormone therapy”, “oestrogen”, “testosterone”, “cancer”, “neoplasm”, “carcinoma”, “screening”, “breast cancer”, “prostate cancer”, “cervical cancer” and “skin cancer”. Reference lists of included articles were also hand-searched to identify additional relevant studies.

Inclusion and exclusion criteria

Studies were included if they were published in English, focussed on TGD individuals and examined the association between GAHT and cancer risk, or discussed cancer screening in this population. Eligible study designs included cohort studies, case control studies, case series, case reports and systematic reviews. Clinical guidelines and recommendations from professional organisations were also included. Studies were excluded if they were not focussed on TGD populations, were not available in English or were editorials or commentaries without original data, unless they provided significant clinical context.

Data extraction and synthesis

Two reviewers independently screened titles and abstracts for eligibility. Full-text articles of potentially relevant studies were retrieved and assessed for inclusion. Disagreements were resolved through discussion and consensus. Data were extracted from included studies into a standardised table encompassing author, year of publication, study design, sample size, key findings and digital object identifier (DOI). Findings were synthesised narratively to provide a comprehensive overview of the current evidence, given the heterogeneity of study designs and outcomes.

Results

The literature search identified 202 records in total. Following the removal of 32 duplicates, 170 records were screened by title and abstract, of which 121 were excluded. Forty-nine full-text articles were assessed for eligibility and 28 were excluded for the following reasons: not focussed on TGD populations (n=8), no cancer outcomes and outcome data (n=5+11), opinion or editorial without original data (n=3) and language other than English (n=1). Thirteen studies were ultimately included in the qualitative synthesis. Key included studies are summarised in Table 1.

Skin cancer risk

The most robust evidence regarding skin cancer risk in TGD individuals receiving GAHT comes from a nationwide cohort study conducted in the Netherlands.⁴ This retrospective study, the largest and most methodologically rigorous examination to date, followed 3,880 transgender individuals (2,436 trans women and 1,444 trans men) through integration of clinical data with national pathology and cancer registries. The analysis found no statistically significant increase in melanoma or squamous cell carcinoma incidence compared to the general population. However, the authors acknowledged important limitations, particularly the relatively short median follow-up periods (8 years for trans women, 4 years for trans men) and the limited proportion of older participants. These factors are significant given that cancer incidence typically increases with age and may require longer exposure periods to manifest.⁴

Evidence from the United States of America All of Us Research Program⁷ provides complementary insights into cancer prevalence patterns among gender minority individuals. This large-scale population-based study represents one of the first examinations of cancer outcomes in gender minority populations within the American healthcare system. The study contributes to the growing body of evidence suggesting that while theoretical concerns about cancer risk exist, empirical data do not support significant increases in common cancer types among TGD individuals receiving GAHT.^2,3 However, these authors also emphasise the importance of continued data collection and longer-term follow-up to establish definitive conclusions about cancer risk.⁷

Although these large-scale studies are reassuring, recent case reports have identified areas of clinical concern that require attention in cancer screening protocols. The first documented case of basal cell carcinoma in a surgically constructed neophallus presents a novel complication of gender-affirming surgery, highlighting the need for dermatological surveillance of surgically created tissues.⁸ This case underscores the importance of including all body surfaces, including surgically altered areas, in routine skin examinations.

Neovaginal cytology and cancer risk

Cytological studies of neovaginal tissues have revealed additional considerations for cancer screening.⁹ Analysis of cytological samples from neovaginas identified abnormal findings including atypical squamous cells of undetermined significance, high-grade squamous intraepithelial lesions and low-grade squamous intraepithelial lesions. Importantly, a statistically significant correlation was observed between the presence of nucleated squamous cells and oestrogen replacement therapy, suggesting that hormonal status influences the cytological characteristics of neovaginal tissues.⁹ These findings have important implications for screening protocols, as they demonstrate that neovaginal tissues can develop premalignant and malignant changes similar to native vaginal tissues.⁹ The authors concluded that individuals with neovaginas should be included in regular cancer screening programmes, though optimal screening protocols remain to be established. It is important to note that recommendations for neovaginal screening are currently based on pragmatic clinical advice and expert opinion, rather than formally mandated guidelines.

Histopathological changes with feminising hormone therapy

Systematic analysis of surgical pathology specimens from transgender women receiving feminising hormone therapy has provided valuable insights into tissue-level changes associated with GAHT.¹⁰ Common benign changes include mammary acini and lobule development in breast tissue, testicular tubular changes and squamous metaplasia of the prostate and urethra.¹⁰ These changes reflect the profound effects of oestrogen and antiandrogen therapy on hormone-sensitive tissues. Neoplastic cases identified in these analyses include breast adenocarcinoma, fibroepithelial lesions, testicular germ cell tumours, prostatic adenocarcinoma, anal squamous cell carcinoma, pituitary adenomas and meningiomas.¹⁰ While these findings do not specifically address skin cancer, they provide important contextual information for understanding the broader oncological implications of hormone therapy and emphasise the need for comprehensive cancer surveillance.

View Figure 1–2, Table 1.

Discussion and recommendations

Organ-based screening framework

The fundamental principle guiding cancer screening in TGD individuals is that screening decisions should be based on the organs present, rather than on an individual’s gender identity or hormonal status.⁶ This organ-based approach is crucial to prevent both over-screening and under-screening in the TGD population.³ The screening framework presented in Figure 1 provides a practical tool for general practitioners to apply this principle in clinical practice.

Pre-treatment counselling and informed consent

Primary care providers have a vital role not only in implementing ongoing screening but also in counselling patients before they embark on gender-affirming therapies. Discussions about the potential long-term health implications of GAHT and gender-affirming surgery, including potential cancer risks, should form an integral part of the informed consent process prior to treatment initiation. While current evidence does not suggest a large increase in overall cancer risk, the potential for altered risk profiles and the emergence of cancers in neotissues are important considerations for patients to understand from the outset.¹¹

Breast cancer screening

Recommendations for breast cancer screening must be aligned with national guidelines in Australia and New Zealand. BreastScreen Australia actively invites individuals aged 50–74 for biennial screening mammograms, with eligibility commencing from age 40.¹² In New Zealand, BreastScreen Aotearoa offers free mammograms every 2 years for women aged 45–69. For trans women, guidelines generally recommend mammographic screening if they have a history of significant oestrogen use (typically 5 or more years) and are within the eligible age range of the relevant national programme.^13,14 For trans men who have not undergone mastectomy, breast screening should continue in accordance with standard guidelines applicable to individuals assigned female at birth.¹⁵

Cervical cancer screening

Cervical cancer screening should be offered to all individuals with a cervix, regardless of gender identity or hormone therapy status, including trans men and non-binary individuals who may face particular barriers to accessing this care.¹⁶ The availability of self-collection for human papillomavirus (HPV) testing under the National Cervical Screening Programme in Australia and New Zealand represents a critical advancement in addressing these barriers and should be actively promoted in general practice.¹⁷

Prostate cancer screening

Prostate cancer screening remains a topic of ongoing debate, with no universal population-based screening programme in either Australia or New Zealand. An informed-choice approach based on individual risk assessment is recommended.¹⁸ For trans women, the available data are sparse but concerning. Emerging evidence suggests that trans women receiving oestrogen therapy may present with higher-grade prostate cancer, potentially due to the absence of a population-specific prostate-specific antigen (PSA) reference range, which complicates interpretation of results.^19,20 An individualised discussion about the risks and benefits of PSA testing is therefore warranted for trans women, particularly those aged 50 years or older, or those aged 45 years or older with additional risk factors.²¹

Skin cancer and surgical site surveillance

Routine whole-body skin examinations should be a standard component of preventive care for all TGD patients. For those who have undergone gender-affirming surgery, careful inspection of surgically altered tissues—including neophalli, neovaginas and skin graft sites—is essential, as the natural history of malignant transformation in these neotissues may differ from native tissues.^8,9 Clinicians should maintain a low threshold for biopsy of any suspicious lesions in these areas. Recommendations for screening of neotissues are currently based on pragmatic clinical advice derived from emerging case reports rather than formally mandated guidelines, and should be framed accordingly in patient discussions.

New Zealand context

Clinicians practicing in New Zealand should be aware of specific local resources and guidelines. The National Cervical Screening Programme in New Zealand includes self-collection options that are particularly relevant for TGD individuals. BreastScreen Aotearoa provides free mammograms for eligible individuals aged 45–69. The New Zealand Cancer Society and Health New Zealand – Te Whatu Ora provide additional resources for LGBTIQA+ communities. General practitioners should familiarise themselves with these local pathways and advocate for inclusive access to screening services for their TGD patients.

Addressing barriers to screening

Existing evidence documents significant disparities in cancer screening participation among TGD individuals, with diagnoses often made at a later stage in the disease continuum.¹⁸ Participation in routine prostate cancer screening has been reported as substantially lower in trans women compared with cisgender men.¹⁹ Creating culturally safe and inclusive practice environments is therefore not merely a matter of comfort but a clinical necessity for improving health outcomes. Key elements of inclusive practice include using chosen names and pronouns, maintaining confidentiality regarding gender identity and transition status and ensuring that all staff members are trained in culturally competent care for TGD individuals.¹ Practice systems should accommodate the unique needs of TGD patients, including flexible appointment scheduling and sensitive handling of medical records.¹⁷

General practitioners play a crucial role in addressing these barriers through advocacy, education and the provision of comprehensive, affirming care.¹ Strategies include developing relationships with local TGD community organisations, participating in continuing education on transgender health and advocating for inclusive healthcare policies at practice and system levels.¹⁷

Implementing these inclusive practices requires institutional commitment, staff training programmes and ongoing quality improvement to ensure that all team members understand and support the care of TGD patients.

Conclusion

General practitioners in Australia and New Zealand are at the forefront of providing comprehensive, inclusive care to TGD individuals. By adopting an organ-based screening framework, maintaining cultural competency and fostering inclusive practice environments, general practitioners can significantly improve preventive health outcomes for their TGD patients. The evidence on long-term cancer risk with GAHT is still evolving, and it is crucial for clinicians to remain informed and adapt their practice as new data emerge. This systematic review provides a current, evidence-based foundation for these clinical decisions, emphasising a patient-centred approach that respects the unique needs and experiences of each individual.