Reassuring evidence that GAHT does not substantially increase overall cancer risk alongside a call for organ-based screening and inclusion.
A review from Charles Sturt University has highlighted disparities in cancer screening participation among transgender and gender-diverse patients, including reports that trans women are less likely to participate in routine prostate cancer screening than cisgender men.
While giving reassurance that gender-affirming hormone therapy (GAHT) is not associated with an increase in overall cancer incidence, the analysis emphasised the need for screening according to anatomy and individual risk factors, rather than gender identity alone.
The review also emphasised that gender-affirming surgery may create new anatomical sites requiring surveillance – a consideration not included in screening guidelines – and highlighted evidence that transgender and gender-diverse (TGD) patients may be diagnosed with cancer at a later stage in the disease course, although the review did not provide pooled estimates quantifying this disparity.
The researchers analysed 13 international studies from countries including Australia, New Zealand, the US, the UK, and the Netherlands, encompassing population-based cohort studies, cytopathology research, and case reports, to assess the latest evidence on cancer risk and screening among TGD patients.
The researchers found no evidence of a substantial increase in overall cancer incidence associated with GAHT across the available data, although the studies were too heterogeneous for pooled analysis. Instead, the review discussed specific cancer types and individual studies, including a nationwide cohort study conducted in the Netherlands that provided the largest and most robust evidence to date on skin cancer incidence among people receiving GAHT.
Among 2436 trans women and 1444 trans men, followed for a median eight years and four years, respectively, there was no statistically significant increase in melanoma or squamous cell carcinoma incidence compared to the general population. However, the researchers noted that relatively few older participants were included, while cancer incidence typically increases with age and some cancers may require longer exposure periods to develop.
Cytological research identified some abnormal findings in neovaginas including atypical squamous cells of undetermined significance, high-grade squamous intraepithelial lesions, and low-grade squamous intraepithelial lesions. They reported a “statistically significant correlation between the presence of nucleated squamous cells and oestrogen replacement therapy”.
The analysis also included a case report which described the first documented basal cell carcinoma arising in a surgically constructed neophallus. While rare, the case highlighted that neotissues, such as neophalli, neovaginas, skin graft sites, and other surgically altered areas, may also develop malignant changes and should be considered during routine examinations.
Currently, recommendations for surveillance of neotissues are not included in formal population-based screening guidelines and are based primarily on emerging case reports and clinical judgement.
Researchers emphasised that longer-term population studies are needed to define the cancer risks associated with lifelong GAHT exposure, as even the most robust studies conducted so far may not capture cancers that develop after decades of exposure. The evidence is also limited by relatively small TGD cohorts and the historical exclusion of transgender populations from many large epidemiological studies.
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“Transgender people on hormone therapy do not have higher rates of common cancers than anyone else – good news that should ease many worries,” said Pasifika Medical Association Group in a media release about the findings.
“However, doctors need to watch for rare cancers in surgically created tissues and keep a closer eye on breast and prostate health in transgender patients. The key is simple: base cancer screening on what organs someone actually has, not on their gender identity or how they look.
“But here is the catch – none of this works if transgender patients do not feel safe and welcomed in their doctor’s office, so creating inclusive, respectful healthcare environments is just as important as the medical screening itself.”
With access to GAHT expanding across Australia and New Zealand, GPs are increasingly involved not only in hormone management but also in the long-term preventive care of TGD patients.
In cisgender populations, clear sex-based differences exist in cancer incidence, suggesting that endogenous hormones contribute to cancer biology, but it is not wholly understood how gender-affirming care impacts this in TGD populations. This uncertainty can create challenges when counselling patients and when determining appropriate screening strategies.
“By combining smart, organ-based screening with genuine cultural respect and inclusivity, doctors can give transgender and gender-diverse patients the cancer prevention care they deserve,” PMA Group concluded.
