Incidence, risk factors and outcomes of de novo malignancies post liver transplantation

Table 1 Summary of study characteristics and reported incidence of de novo malignancy post liver transplantation in large series

Ref.	Year published	Country of study center	Study period	No. of liver transplant recipients	4Duration of follow-up (yr)	4Age at transplant in patients with de novo malignancy (yr)	Proportion of males with de novo malignancy	4Interval to de novo malignancy (yr)	Overall incidence of de novo malignancy (number of patients)	5/10/15 and 20 yr incidence of de novo malignancy	Estimated overall risk relative to control population
Jonas et al[28]	1997	Germany	1988-1994	458	4.2	46 ± 14	48%	3.6	7.2% (33)	14.6%/-/-/-	-
Jain et al[3]	1998	United States	1996-2006	1000	6.5 ± 1	Approximately 56	77%	3	5.7% (57)	-	SIR calculated for specific cancer types
Kelly et al[25]	1998	United Kingdom	1988-1996	888	-	Approximately 52	46%	2 ± 1.5	24.4% (29)	-	-
Galve et al[116]	1999	Spain	1984-1997	1827	-	-	-	2.5 ± 1.8	3.8% (70)	-	-
Haagsma et al[8]	2001	The Netherlands	1979-1996	174	5.1	Approximately 49	29%	5.9	12% (21)	6%/20%/55%/-	RR = 4.3 (95%CI: 2.4-7.1)
Sanchez et al[5]	2002	United States	1985-1999	1421	5.5 ± 3.7	50 ± 12	55%	-	8.8% (125)	-	-
Saigal et al[4]	2003	United Kingdom	1988-1999	1140	-	51.5	70%	3.8 ± 2.8	2.6% (30)	-	-
Benlloch et al[36]	2004	Spain	1991-2001	772	4.3	50	59%	3.5	5.3% (41)1	-	-
Oo et al[45]	2005	United Kingdom	1982-2004	1778	6.5	-	43%	-	7.9% (141)	-	SIR = 2.1 (95%CI: 1.7-2.2)
Herrero et al[7]	2005	Spain	1990-2001	187	5.5	-	-	-	26% (49)	25%/39%/-/-	RR = 2.9 (95%CI: 1.6-5.0)
Yao et al[40]	2006	United States	1988-2000	1043	6.7	53.2	52%	-	4.8% (50)	-	-
Aberg et al[9]	2008	Finland	1982-2005	540	6.3	-	53%	5.1	6.7% (36)3	5%/13%/-/16%	3SIR = 2.6 (95%CI: 1.8-3.5)
Jiang et al[10]	2008	Canada	1983-1998	2034	-	-	53%	3.5 ± 2.8	5.5% (113)1	2%/8.6%/-/-	1SIR = 2.5 (95%CI: 2.1-3.0)
Watt et al[12]	2009	United States	1990-1994	798	10	-	60%1	-	21.4% (171)	12%/22%/-/-	-
Finkenstedt et al[18]	2009	Austria	1982-2007	779	4.1	-	-	4.4	12.3% (96)	10%/24%/32%/42%	1SIR = 1.9 (95%CI: 1.5-2.4)
Baccarani et al[17]	2010	Italy	1991-2005	417	6.7	-	74%	4.2	10.3% (43)1	-	1SIR = 2.6 (95%CI: 1.9-3.6)
Tjon et al[27]	2010	Denmark	198-2007	85	5	-	-	-	3% (50)	10%/19%/34%/-	SIR = 2.2 (95%CI: 1.6-2.8)
Park et al[67]	2012	South Korea	1998-2008	1952	3.5 ± 2.8	56	79%	3.4 ± 2.4	2.3% (44)1	-	1RR = 7.7 for men and 7.3 for women
Chatrath et al[2]	2013	United States	1997-2004	534	5.7 ± 3.2	53 ± 12	67%	4 ± 2.2	13.7% (73)	12%/25%/-/-	1SIR = 3.1 (95%CI: 2.9-3.2)
Wimmer et al[24]	2013	Germany	1985-2007	609	5.2	53 ± 10	73%	5.7	11.5% (70)	10%/26%/35%/-	-
Ettorre et al[11]	2014	Italy	1990-2008	1675	5.2	-	-	3.2	5.9% (98)1	-	1SIR = 1.4 (95%CI: 1.2-1.7)
Yu et al[69]	2014	China	2005-2011	569	3.5 ± 2.2	-	76%	-	3.2% (17)	-	-
Antinucci et al[117]	2015	Argentina	2006-2014	168	-	67 ± 7	75%	1.3	7.5% (12)	-	-
Sanaei et al[68]	2015	Iran	1992-2012	1700	-	34 ± 10	63%	5.5	2.2% (38)	-	-
Overall means				940	5.5	52	61%	3.8	8.10%	11%/22%/39%/29%	3.0

¹Excluding non-melanoma skin cancers;

²Excluding post-transplant lymphoproliferative disorder;

³Excluding basal cell skin cancer; ⁴Median or mean ± SD. SIR: Standardized incidence ratio.

Table 2 A listing on known oncogenic viruses and the malignancies associated with them

Oncogenic virus	Associated malignancy
EBV	PTLD
Human papilloma virus	Cervical, skin, oropharynx, anal
Human T-cell lymphotropic virus type 1	Adult T cell leukemia
Kaposi’s sarcoma-associated herpesvirus	KS, primary effusion lymphoma, castleman's disease
HBV	HCC
HCV	HCC, PTLD1

¹Role controversial. HCC: Hepatocellular carcinoma; EBV: Epstein-Barr virus; PTLD: Post transplant lymphoproliferative disorder; KS: Kaposi’s sarcoma; HBV: Hepatitis B virus; HCV: Hepatitis C virus.

Table 3 A summary of ranges of reported overall incidence rates and standardized incidence ratios of a number of cancer types following liver transplantation[2-5,7-12,14-16,28,36,47,66,110,118-120]

	Incidence (%)	SIR
Skin cancers
Represent 24%-54% of all cancers, average 37%
Overall (non-melanoma)	0.9-11.6	2.1-70, average 24
Squamous cell cancer	0.6-15.3	Not reported
Basal cell cancer	0.6-10.6	Not reported
KS	0.2-1.4	128-144
Melanoma	0.2-3.9	4.4
Post-transplant lymphoproliferative disorders
Represent 4%-57% of all cancers, average 25%
Overall	0.5-2.9	3.9-21, average 12
Hodgkin’s lymphoma	0.001-0.4	8.2-8.9
Non-Hodgkin's lymphoma	0.8-3.7	3.5-37.3
Solid organ cancers
Represent 24%-75% of all cancers, average 48%
Overall	1.4-7.5	1.4-3.1, average 2.3
Lip	1.8	14-24.8
Oropharyngeal	1.7-1.9	7-10
Lung	0.6-2.4	1.4-2.0
Stomach	0.2-0.7	0.5-3.7
Colorectal	0.5-1.1	1.4-4.9
Breast (in females)	0.2-0.6	0.6-1.61
Cervix (in females)	0.7-1.4	1.3-5.7
Prostate (in males)	0.2-1.8	0.6-1.61

¹The SIR was not found to be significantly higher for transplant recipients compared with the reference population. Of note, studies often reported either incidence rate or SIR, but rarely both values. SIR: Standardized incidence ratio; KS: Kaposi’s sarcoma.