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risk for colorectal cancer and those with alcohol-associated liver disease are at
increased risk for esophageal and head/neck cancers compared with patients under-
going lung transplants for other indications [4].
Risk factors for cancer in solid organ transplant recipients include immunosup-
pression, oncogenic viruses, and disease-specic associations. Traditional risk fac-
tors such as tobacco use, sun exposure, and history of cancer are also important.
(See Chap. 10, Table 10.2.) Donor-derived malignancy rarely occurs.
Cancers in solid organ transplant recipients are often more advanced at diagno-
sis, more aggressive and difcult to treat, and have worse outcomes than the general
population [5]. Unfortunately, the optimal screening strategy remains uncertain as
randomized controlled cancer screening trials have not been performed in the solid
organ transplant population. Furthermore, screening trials that might improve out-
comes are unlikely to be conducted given the small population size of solid organ
transplant recipients.
A systematic review of 12 clinical practice guidelines for adult solid organ trans-
plant recipients found that although most of the guidelines made recommendations
for cancer screening, they varied considerably by transplanted organ, were largely
based on expert opinion, and were derived primarily from cancer screening guide-
lines for the general population [6]. Although there is increased risk for multiple
types of cancers in solid organ transplant recipients, screening guidelines specic to
solid organ transplant recipients have only been developed for a limited number of
the cancers, including skin, cervical, anal, and liver cancer. While other cancers
contribute to signicant morbidity and mortality, to date there has not been evidence
demonstrating that screening for cancers not screened for in the general population
(e.g., post-transplant lymphoproliferative disorder [PTLD], kidney cancer) [7] or
increasing intensity of screening for other cancers (e.g., colorectal cancer) improves
outcomes. Barriers to developing additional screening methods include a lower
overall number of research subjects and a decreased life expectancy compared to the
general population.
14.1.1 Skin Cancer Screening
Nonmelanoma skin cancers are among the most common of all malignancies in
solid organ transplant recipients. The risk of cutaneous squamous cell carcinoma
(SCC) is 65 times that of the general population and the risk is 3-fold for malignant
melanoma (MM) [3]. Risk factors include male gender, fair skin, sun exposure,
geographic location, history of previous nonmelanoma skin cancer, age 50years or
older at the time of transplant, a recipient of a thoracic organ, and having a longer
time elapsed since transplant [3].
Squamous cell cancers tend to develop at a younger age, are more aggressive,
and metastasize more often compared to the general population [8]. Primary care
providers should have a low threshold to biopsy any suspicious lesion and aggres-
sively treat actinic keratoses or other precancerous lesions. Patients should be
R. S. Gold and L. Marcotte
399
advised to seek evaluation for any new skin lesion as soon as it is noticed, minimize
sun exposure, and always use sunscreen and wear sun-protective clothing such as
hats. Most clinical practice guidelines for solid organ transplant recipients recom-
mend annual skin and lip cancer screening by either a primary care physician or
dermatologist [6]. These recommendations contrast with those of the US Preventive
Services Task Force (USPSTF) for the general population, which cite insufcient
evidence to recommend for or against skin cancer screening [9].
A study group surveyed 84 dermatologists and transplant physicians in the US to
help develop expert consensus guidelines on when to start skin cancer screening
after transplant [10]. This group recommends risk stratication by the transplant
team to inform initiation of full-body skin exams post-transplant. For example,
high-risk patients with low melanin content in skin should be screened within
2years of transplant. This same study group also developed a tool called the Skin
and Ultraviolet Neoplasia Transplant Risk Assessment Calculator (SUNTRAC), to
individualize care and assist in patient risk assessment for determining when patients
should have a rst skin exam [11].
A diagnosis of cutaneous SCC is associated with a higher risk of subsequently
developing a non-cutaneous SCC [8]. These include cancers of the oral cavity/phar-
ynx, lip, tongue, lung and HPV-related cancers (anal and lower genital cancers).
Therefore, it is important for primary care providers to be diligent in evaluating any
new symptoms that arise in these areas if a solid organ transplant recipient has a
history of cutaneous SCC.
14.1.2 Cervical Cancer Screening
Cervical intraepithelial neoplasia (CIN) has been shown to be increased in solid
organ transplant recipients. Prior studies analyzing all types of solid organ trans-
plant showed mixed results for risk of cervical cancer (i.e., increased in some
studies but not others), likely in part due to differences in screening and treatment
of precancerous lesions, with standardized incidence ratios ranging from 2 to 6
compared to the general population [12] (See Chap. 10). However, the review of
data specic for renal, heart/lung, liver, and pancreas transplants showed a more
consistent increase in risk. The direct effect of specic immunosuppressants on
gynecologic cancers is not well-studied and data is conicting [13]. Although
some studies have suggested that degree and type of immunosuppression may
impact risk for development of high grade, CIN grade 2 or higher (CIN2+) lesions.
General risk factors for developing squamous cell HPV-related cancers of the
cervix, vulva, and vagina include multiple sexual partners or partners with multi-
ple sexual partners, current tobacco use, and infection with other sexually trans-
mitted diseases.
Recommendations for cervical cancer screening among non-HIV immunosup-
pressed women remain limited because of a lack of quality studies. The 2018
USPSTF guidelines on cervical cancer screening do not include recommendations
14 Preventive Health intheAdult Solid Organ Transplant Recipient
400
for solid organ transplant recipients. In the review of clinical practice guideline
recommendations for solid organ transplant recipients, eight of 12 guidelines rec-
ommended cervical cancer screening but with varying screening intervals: two rec-
ommended screening every 3years, ve recommended annual screening, and one
recommended screening every 3–5years [6].
A panel of cervical cancer researchers concluded that there is a consistent
increase in the risk of cervical neoplasia and invasive cervical cancer in kidney,
heart, lung, liver, and pancreas transplant recipients, and that using the Center for
Disease Control (CDC) cervical cancer screening guidelines for women with
HIV was a reasonable approach for screening and surveillance in the solid organ
transplant population [12]. Cervical cancer screening recommendations among
women with HIV have been supported by evidence from retrospective and pro-
spective studies. The purpose of more frequent screening than the general popu-
lation is to identify low-grade lesions before progression to high-grade squamous
intraepithelial lesions or carcinoma. These recommendations are given in
Table14.1 [13].
The American Society of Transplantation (AST) Infectious Diseases Community
of Practice guidelines recommend more frequent screening using Pap testing every
6 months for the rst year, then annually indenitely if rst tests are negative;
although authors note this is a weak recommendation based on low-quality evidence
(Table14.1) [14]. These guidelines also provide the option of high-risk HPV test-
ing. Patients with positive tests are recommended to continue every 6-month testing,
while those with negative high-risk HPV tests may decrease to yearly screening.
AST suggests changing screening frequency back to every 6months if a patient has
been treated for rejection, necessitating an increased level of immunosuppression.
Because of these differences in screening recommendations, cervical cancer
screening (e.g., test, type, and frequency) should be discussed with the patient after
reviewing the potential benet, risks of harm, and their personal preferences.
Individual transplant centers may also have preferences for cervical cancer
screening.
The decision to discontinue screening should be made based on comorbidities,
life expectancy, and personal factors. If a patient undergoes a hysterectomy with
removal of the cervix for benign disease and has no history of CIN2+, then ongoing
routine screening for cervical or vaginal cancer is generally not recommended,
although this is largely based on practices for patients with HIV [13]. Although less
common than cervical or anal cancer, a higher incidence of vulvar and vaginal can-
cer has been reported in transplant recipients compared to the general population
[14]. However, we do not yet have data or specic guidelines to support screening
for vaginal or vulvar cancers in this population.
R. S. Gold and L. Marcotte
401
Table 14.1
Cancer screening recommendations in adult solid organ transplant recipients
Type of
cancer
screening
Recommendation for solid organ
transplant recipients
a
Comment
Skin cancer Annual skin exam General population: insufcient evidence
to recommend for or against routine skin
cancer screening in average-risk
individuals
Cervical
cancer
Moscicki, etal: [12]
Women < age 30:
– Annual cytology
– If three consecutive cytology tests
normal, then repeat every 3years
Women ≥ age 30:
– Annual cytology; if three
consecutive tests are normal, then
repeat testing every 3years
-or-
– Cytology and HPV co-testing at
baseline; if both normal, then
repeat co-testing every 3years
AST: [14]
– Pap testing every 6months for the
rst year after transplant, then
annually indenitely
– Increase frequency to every
6months if treated for rejection
Moscicki etal. recommendations are
similar to those for patients with HIV [13];
AST guidelines recommend yearly
screening interval indenitely.
All guidelines recommend continuing
screening regardless of age (unlike the age
65 upper limit for cervical cancer screening
in the general population).
Due to increased risk for other HPV-
associated cancers, at the time of cervical
cancer screening, recommend inspection of
the anus, vulva, and vagina for concerning
lesions or skin changes.
Anal cancer Annual cytology, with emphasis on
testing patients who are high-risk:
– History of receptive anal
intercourse
– History of cervical dysplasia
Approach is similar to recommendations
for patients with HIV [13].
Anal cytology is paired with high-
resolution anoscopy (HRA) for positive
tests; this approach is dependent on local
infrastructure (equipment, trained
providers, and pathologists).
Liver
cancer
Kidney transplant recipients:
AFP, ultrasound every 6–12months
if history of cirrhosis, chronic HBV,
or chronic HCV infection [6]
Liver transplant recipients:
– NCCN: AFP; CT or MRI every
3–12months if history of prior
HCC [16]
– AASLD: US every 6–12months if
develop allograft cirrhosis [17]
Patients with cirrhosis in the general
population are also recommended to
undergo HCC screening.
AASLD American Association for the Study of Liver Disease, AFP alpha-fetoprotein, AST
American Society of Transplantation, HBV viral hepatitis B, HCC hepatocellular carcinoma, HCV
viral hepatitis C, HPV human papilloma virus, NCCN National Comprehensive Cancer Network,
US ultrasound
a
Shown are selected examples; guidelines vary [6]
14 Preventive Health intheAdult Solid Organ Transplant Recipient
402
14.1.3 Anal Cancer Screening
Similar to cervical cancer, persistent infection with oncogenic HPV predisposes to
anal precancerous lesions and SCC.There have been no randomized clinical trials
documenting the value of screening for anal SCC in at-risk populations. However, a
systematic review demonstrated the increased incidence of anal HPV infection, anal
precancerous lesions, and anal SCC among solid organ transplant recipients com-
pared to the general population [15]. As such, the AST guidelines [14] recommend
yearly anal cancer screening using anal cytology, with emphasis on testing patients
with a history of receptive anal intercourse or cervical dysplasia. The AST guide-
lines note that this is a weak recommendation, based on low-quality evidence and
largely informed by screening recommendations for HIV-positive patients. Patients
who are found to have squamous cytological abnormalities on screening should be
referred for high-resolution anoscopy (HRA). However, this screening approach is
only recommended if there is sufcient infrastructure, including experienced
pathologists, HRA equipment, and staff trained in its use. Overall data is still lim-
ited regarding when to initiate screening, method of screening, frequency of screen-
ing, and the risk pattern of particular immunosuppressive therapies.
14.1.4 Liver Cancer Screening (For Kidney andLiver
Transplant Recipients)
In the large 2017 systematic review [6], six of 12 clinical practice guidelines recom-
mended liver cancer screening with ultrasound and serum alpha-fetoprotein (AFP)
every 6–12months in kidney transplant recipients who have cirrhosis or who are
high-risk for developing liver cancer, including recipients with chronic hepatitis B
virus (HBV) or hepatitis C virus (HCV) infection.
A newer 2022 review also comments on screening among liver transplant recipi-
ents, with the main focus on detecting tumor recurrence in recipients with a history
of hepatocellular carcinoma (HCC) [7]. Among liver transplant recipients, most
liver cancers are diagnosed within the rst 6months, perhaps suggesting identica-
tion of previously subclinical malignancy. Later post-transplant occurrence is more
common among those with a previous HCC diagnosis and likely represents recur-
rence, which is often metastatic when identied. There is little consensus on optimal
modality or frequency for liver cancer screening in liver transplant recipients. For
patients with a history of HCC, the National Comprehensive Cancer Network
(NCCN) suggests CT or MRI and serum AFP every 3–12months [16]. CT and MRI
are preferred in higher risk individuals because ultrasound has lower sensitivity for
small nodules [7]. In contrast, the American Association for the Study of Liver
Disease (AASLD) recommends ultrasound every 6–12months in recipients without
a history of HCC who develop recurrent cirrhosis of the allograft to screen for de
novo disease [17].
R. S. Gold and L. Marcotte
403
14.1.5 Colorectal Cancer Screening
Colorectal cancer screening recommendations for solid organ transplant recipients
generally follow guidelines for the general population [6, 7]. However, a solid organ
transplant recipient should be considered to be at higher risk for colorectal cancer,
with a standardized incidence ratio of between 1.1 and 2.7 times that of the general
population (See Chap. 10). This magnitude of risk is comparable to that of a person
with a family history of colorectal cancer in a rst-degree relative (relative risk 1.9)
[18], and for whom colonoscopy is recommended as the preferred screening modal-
ity [19]. Additionally, solid organ transplant recipients have an increased risk of
proximal colorectal cancers (Chap. 10), which have lower detection rates using
immunochemical stool-based tests compared to colonoscopy. Despite these consid-
erations, which would favor colonoscopy, there is not data to support colonoscopy
over other screening modalities in solid organ transplant recipients specically. The
potential advantages of colonoscopy must be weighed against the risk of the proce-
dure—which may also be higher in solid organ transplant recipients—and tailored
to a patient’s individual preferences. Patients with cystic brosis have a particularly
high risk of colorectal cancer after transplantation—specic guidelines have been
published for earlier screening in this population [20].
14.1.6 Post-transplant Lymphoproliferative Disorder
(PTLD) Screening
PTLD is one of the most serious complications for solid organ transplant recipients,
because of its prevalence, morbidity, mortality, and challenges to treatment.
Unfortunately, there are no trials or consensus recommendations for screening for
PTLD. While practices vary, some transplant centers check Epstein–Barr virus
(EBV) serum PCRs in solid organ transplant recipients who are at risk, while other
authors additionally recommend screening by history and physical in the rst
3months post-transplant, and then yearly thereafter [7].
Table 14.1 summarizes cancer screening in solid organ transplant recipients. See
also Chap. 10 for further discussion.
14.1.7 Adherence toCancer Screening inSolid Organ
Transplant Recipients
Adherence to cancer screening has not been well-studied in solid organ transplant
recipients; however, the available evidence is concerning for low screening rates. A
large population cohort in Canada was studied between 1997 and 2010 to determine
the uptake of breast, cervical, and colorectal cancer screening [21]. They found that
4436 were eligible for colorectal screening, 2252 for cervical cancer screening, and
14 Preventive Health intheAdult Solid Organ Transplant Recipient
404
1551 for breast cancer screening. Of those, 77.5%, 69.8%, and 91.4%, respectively,
were not up-to-date on cancer screening tests during the observed period. More
surprisingly, greater than 30% had not been screened at all during the study period
for colorectal, cervical, and breast cancer. The screening rates were lower than in
the general population. Similarly, a small hospital-based cohort of kidney transplant
recipients diagnosed with cancer in Jordan (n=39) was surveyed and only 8% were
up-to-date on guideline recommended cancer screening [22].
The reason for these low screening rates is not known but it does suggest that
there is room for signicant improvement and better communication between trans-
plant specialists and primary care providers in the routine care of these patients. For
example, a cross-sectional survey of 477 physicians and nurses who provide care to
solid organ transplant recipients in Canada found that although providers viewed
skin cancer screening as important (median rating of 10/10), only 53% ensured
annual screening occurred [23]. In further exploration of barriers and facilitators to
screening, this study found that having a screening policy in place and a dermatolo-
gist present in the transplant center were independently associated with higher
adherence, while longer wait-times and travel distance, lack of transplant derma-
tologists, and “insufcient priority” were the most commonly cited barriers.
14.2 Risk ofCardiovascular Disease andDiabetes
Solid organ transplant recipients are at increased risk for cardiovascular disease
(CVD), and in many solid organ transplant populations, cardiovascular disease is a
leading cause of non-graft related death [17, 24]. In a review of managing CVD risk
[25], the authors categorized risk factors into four categories: pre-transplant risk
factors (including usual risk factors, e.g., hypertension, hyperlipidemia, diabetes,
and tobacco use), transplant-related risk factors (e.g., glucocorticoid-associated
obesity, immunosuppression, graft dysfunction, rejection, anemia), donor risk fac-
tors (e.g., age of donor, quality of organ donated, ischemic time prior to transplanta-
tion), and other risk factors (e.g., increased C-reactive protein, prothrombosis,
proteinuria). Although transplant-related and donor risk factors are generally not
modiable, it is important to consider these non-traditional factors in solid organ
transplant recipients so as not to underestimate CVD risk. For example, patients
with chronic kidney disease may have volume overload that leads to left ventricular
hypertrophy, which has been shown to be associated with increased cardiovascular
disease events in kidney transplant recipients [26]. As a result of the unique risk
factors related to solid organ transplantation, traditional risk models, such as the
Framingham Heart Study risk score, tend to underestimate CVD risk in solid organ
transplant recipients [27]. The pooled cohort equations recommended in the
American Heart Association/American College of Cardiology guidelines [28] have
not been studied in solid organ transplant recipients.
As multiple non-traditional and often non-modiable factors contribute to solid
organ transplant recipients’ overall CVD risk, it is important for primary care pro-
viders to identify and manage modiable risk factors such as hypertension,
R. S. Gold and L. Marcotte
405
hyperlipidemia, obesity, diabetes, and tobacco use. Even adjusting for transplant-
specic risk factors, solid organ transplant recipients are at increased risk for the
usual risk factors above [25].
Transplant medications can lead to multiple side effects increasing risk for car-
diovascular disease: hypertension (calcineurin inhibitors and steroids), dyslipid-
emia (steroids and mammalian target of rapamycin [mTOR] inhibitors),
post-transplant diabetes (calcineurin inhibitors, glucocorticoids, and mTOR inhibi-
tors), and anemia (mycophenolate and azathioprine) [24]. Calcineurin inhibitors are
also associated with increased risk of hypomagnesemia and hyperuricemia [29].
(See Chap. 3).
Given the frequency of routine lab testing and ofce visits for solid organ trans-
plant recipients by their transplant specialists, much of the data needed for screen-
ing for these conditions will be ordered by the transplant team and can be reviewed
in primary care. However, the primary care provider should ensure that blood pres-
sure is monitored at each visit, lipids are measured, and diabetes is screened for
annually. Counseling patients on the benets of tobacco cessation, regular exercise,
and maintaining a healthy diet is very important.
Recommendations for the assessment of cardiovascular risk and diabetes at out-
patient clinic visits are given in Table 14.2. Management of cardiovascular risk
Table 14.2 Routine outpatient assessment of cardiovascular risk and diabetes in solid organ
transplant recipients
History
Review risk factors including:
Tobacco, alcohol
Exercise
Nutrition
Review symptoms of cardiovascular disease including:
– Angina (note: heart transplant recipients have a denervated organ and may not present with
typical angina)
– Dyspnea
– Edema
– Claudication
Exam
Blood pressure, height, weight
Cardiopulmonary exam
Laboratory
Often ordered routinely by the transplant team
Diabetes screening every 3months for the rst year, then yearly if normal
Lipid panel annually if normal
Other testing
Heart transplant recipients: review surveillance for cardiac allograft vasculopathy
Risk stratication
Existing risk tools may underestimate risk in solid organ transplant recipients.
Chemoprevention (See Chap. 11)
Aspirin used in all heart transplant recipients; variable use in kidney transplant recipients
Statin therapy used in all heart transplant recipients; commonly used in kidney transplant recipients
14 Preventive Health intheAdult Solid Organ Transplant Recipient
406
factors, including the use of aspirin and statins for primary prevention, and treat-
ment of hypertension and dyslipidemia, is addressed in Chap. 11.
14.3 Metabolic Bone Disease
Solid organ transplant recipients are at signicantly increased risk for osteoporosis.
Osteoporosis risk includes pre-transplant bone disease or other pre-existing factors
(e.g., tobacco use, poor nutrition, and vitamin D deciency) as well as transplant-
specic factors such as corticosteroids and possibly calcineurin inhibitors [30]. This
risk is particularly increased within the rst 6 to 12months of organ transplantation
coinciding with higher doses of corticosteroids.
14.3.1 All Solid Organ Transplant Recipients—History
At outpatient visits, the primary care provider should assess risk factors for
osteoporosis:
• Tobacco use: Regular screening for tobacco use is important, because while
active use is regularly monitored prior to (and most often a contraindication for)
transplantation, some patients will return to use following their transplant sur-
gery. Tobacco use and alcohol consumption can compound the risk for bone loss
after solid organ transplantation [31].
• Alcohol use: While alcohol use has been most studied in liver transplant recipi-
ents, alcohol use can have adverse effects in all patients following transplant. In
addition to other health risks, alcohol useis associated with osteoporosis [32].
• Physical activity: Solid organ transplant recipients should be counseled to prac-
tice regular resistance training and weight-bearing exercises, unless contraindi-
cated by their medical conditions. A pilot study of 30 lung transplant recipients
found that resistance exercise plus alendronate was more effective than alendro-
nate alone in restoring bone mineral density (BMD) [33].
• Medications: Corticosteroid use is typically lowered over time, and in lower risk
transplants (e.g., liver) often can be discontinued completely. However, patients
may receive higher doses of corticosteroids for longer periods of time, or inde-
nitely, if they have multiple episodes of rejection, or other indications for use.
Increased exposure to corticosteroids may warrant more frequent BMD testing.
Other medications not related to transplantation should be reviewed for risk of
lowering BMD (e.g., depot medroxyprogesterone for contraception, certain anti-
epileptic medications, high-dose acid suppressive medications—commonly used
in lung transplantation, thiazolidinediones for diabetes).
• Malabsorption: Some solid organ transplant recipients have continued risk fac-
tors for malabsorption. For example, a lung transplant recipient who has cystic
R. S. Gold and L. Marcotte
407
brosis may continue to have signicant gastrointestinal disease, or a liver trans-
plant recipient for primary sclerosing cholangitis may have ongoing inamma-
tory bowel disease symptoms after transplantation. Mycophenolate therapy
commonly causes mild to moderate diarrhea, and rarely can also cause an entero-
colitis with malabsorption.
• Nutrition and body weight: Many solid organ transplant recipients have dif-
culty maintaining body weight prior to transplantation due to cachexia from their
organ failure. After transplantation they should be monitored closely for mainte-
nance of normal body weight.
• Family history: Although non-modiable, the patient’s family history of fracture,
particularly of thehip, should be reviewed.
• Personal history: Patients should be asked about a prior history of fracture. When
the solid organ transplant recipient presents for an initial primary care visit, it is
advisable to review the pre-transplant workup, as most transplant recipients will
have received BMD testing prior to transplantation (See Chap. 2).
14.3.2 Screening Tests andPreventive Therapy
While guidelines for average-risk adults recommend screening dual-energy X-ray
absorptiometry (DXA) to assess BMD for women starting at 65years old or earlier
if equivalent risk, and continuing interval screening depending on baseline risk [34],
in general, all solid organ transplant recipients should be screened with DXA scans
within the rst-year post-transplant. Following initial screening, guidelines vary
with regards to suggested interval screening depending on risk factors and which
organ is transplanted (Table14.3).
• Liver transplant recipients: The 2012 AASLD and AST guidelines [17] recom-
mend continuing screening every 2–3years for liver transplant recipients with-
out osteopenia and annually if osteopenia is present for the rst 5years following
transplant. These guidelines also recommend all post-liver transplant patients
with or at risk for osteopenia take 1000–1200mg daily calcium supplementation,
maintain vitamin D levels above 30ng/mL and engage in regular, weight-bearing
exercise.
• Heart transplant recipients: The updated 2023 International Society for Heart
and Lung Transplantation (ISHLT) practice guidelines [35] recommend screen-
ing with a DXA scan as part of the pre-transplant evaluation. All adult heart
transplant recipients should have recommended age-appropriate daily allowance
of calcium and vitamin D, with weight-bearing and resistance training exercise.
Surveillance DXA should be completed within 12months after transplant and
annually afterwards for patients receiving corticosteroids and/or bisphosphonate
therapy.
• Bisphosphonate therapy within the rst year after transplant may reduce fracture
risk. A meta-analysis including 425 heart transplant patients found that bisphos-
14 Preventive Health intheAdult Solid Organ Transplant Recipient