Human papillomavirus and post-transplant cutaneous squamous-cell carcinoma: a multicenter, prospective cohort study

Organ transplant recipients (OTRs) have a 100‐fold increased risk of cutaneous squamous cell carcinoma (cSCC). We prospectively evaluated the association between β genus human papillomaviruses (βPV) and keratinocyte carcinoma in OTRs. Two OTR cohorts without cSCC were assembled: cohort 1 was transplanted in 2003‐2006 (n = 274) and cohort 2 was transplanted in 1986‐2002 (n = 352). Participants were followed until death or cessation of follow‐up in 2016. βPV infection was assessed in eyebrow hair by using polymerase chain reaction–based methods. βPV IgG seroresponses were determined with multiplex serology. A competing risk model with delayed entry was used to estimate cumulative incidence of histologically proven cSCC and the effect of βPV by using a multivariable Cox regression model. Results are reported as adjusted hazard ratios (HRs). OTRs with 5 or more different βPV types in eyebrow hair had 1.7 times the risk of cSCC vs OTRs with 0 to 4 different types (HR 1.7, 95% confidence interval 1.1‐2.6). A similar risk was seen with high βPV loads (HR 1.8, 95% confidence interval 1.2‐2.8). No significant associations were seen between serum antibodies and cSCC or between βPV and basal cell carcinoma. The diversity and load of βPV types in eyebrow hair are associated with cSCC risk in OTRs, providing evidence that βPV is associated with cSCC carcinogenesis and may present a target for future preventive strategies

Keratotic skin lesions and other risk factors are associated with skin cancer in organ-transplant recipients: a case-control study in The Netherlands, United Kingdom, Germany, France, and Italy.

This study examines the association of keratotic skin lesions with the development of skin cancer in 915 solid organ-transplant recipients in five European countries. In a hospital-based case\u2013control study, cases with squamous- and basal-cell carcinoma were compared with controls without skin cancer. Questionnaires, scrutiny of medical charts, and skin examination were delivered according to a standardized protocol. Keratotic skin lesions and viral warts were counted on different body sites. Keratotic skin lesions were strongly associated with an increased risk of squamous-cell carcinoma, with adjusted odds ratios of 4.1 (2.4;7.0) and 12.1 (6.1;24) for 1\u201349 and 50 and more keratotic skin lesions compared with no lesions, respectively. Keratotic skin lesions were also associated with basal-cell carcinoma with adjusted odds ratios of 2.9 (1.7;4.9) and 4.0 (1.7;9.2) for 1\u201349 and 50 and more lesions, respectively. Lighter skin types and painful sunburns were also significantly associated with an increased risk of squamous- and basal-cell carcinoma. Keratotic skin lesions are strongly associated with skin cancer and are, thus, an important clinical criterion for identifying those organ-transplant recipients at an increased risk of skin cancers who should be offered more intensive skin surveillanc

Beta-papillomavirus DNA loads in hair follicles of immunocompetent people and organ transplant recipients

There is increasing evidence of an association between human papillomaviruses (HPV) of the beta-genus (beta-PV) and the development of cutaneous squamous cell carcinoma (SCC). The viral DNA load may be an important determinant of pathogenicity, but there are currently no baseline epidemiological data relating to load in people without SCC. We investigated DNA-loads of eight beta-PV types previously associated with risk of SCC. We collected eyebrow hairs from immunocompetent people (ICP) and organ transplant recipients (OTR), determined load by quantitative PCR and obtained demographic, phenotypic, and sun exposure information. Viral loads for ICP from Australia (n = 241) and Italy (n = 223) and OTR from across Europe (n = 318) spanned seven orders of magnitude. The median loads for all types were below one viral DNA copy per 60 cells and were highest for HPV5, HPV8 and HPV20. None of the populations had consistently higher viral loads for all 8 types. However, a higher proportion of OTR were in the top deciles of viral load distributions for six of the eight beta-PV types examined. In a nested analysis of Italian OTR and ICP, this finding was significant for six beta-PV types and cumulative load. Increasing age was significantly associated with higher viral loads in Australia, and there was a weak trend for higher loads with the time elapsed since transplantation in the OTR. We observed a wide distribution of beta-PV loads with OTR significantly more likely to have the highest viral loads. Thus, viral loads may be an important contributor to the higher risk of SCC in OTR

Longitudinal study of seroprevalence and serostability of 34 human papillomavirus types in European organ transplant recipients

Organ transplant recipients (OTR) are at increased risk of cutaneous squamous cell carcinoma, which may be related to reactivation of human papillomavirus (HPV) infections. Measurement of change in HPV antibodies after transplantation would help to explore this hypothesis. We measured antibodies to 34 HPV types on up to six occasions over 18 months in 441 OTRs from five European countries. At baseline (mean 24 days after transplantation), 80% of all OTRs were seropositive to at least one HPV type. The beta HPV genus had the highest seroprevalence (45%). For most HPV genera baseline seroprevalence peaked between 40 and 59 years old. Most OTRs retained their serostatus over time and antibody levels were stable. Seroprevalence in immunosuppressed OTRs is stable in the 18 months immediately after transplantation. Thus there is no short-term evidence that immunosuppression leads to new or reactivated skin infection with HPV sufficient to induce antibodies

Human papillomavirus and posttransplantation cutaneous squamous cell carcinoma: a multicenter, prospective cohort study

Organ transplant recipients (OTRs) have a 100- fold increased risk of cutaneous squamous cell carcinoma (cSCC). We prospectively evaluated the association between β genus human papillomaviruses (βPV) and keratinocyte carcinoma in OTRs. Two OTR cohorts without cSCC were assembled: cohort 1 was transplanted in 2003-2006 (n = 274) and cohort 2 was transplanted in 1986-2002 (n = 352). Participants were followed until death or cessation of follow-up in 2016. βPV infection was assessed in eyebrow hair by using polymerase chain reaction–based methods. βPV IgG seroresponses were determined with multiplex serology. A competing risk model with delayed entry was used to estimate cumulative incidence of histologically proven cSCC and the effect of βPV by using a multivariable Cox regression model. Results are reported as adjusted hazard ratios (HRs). OTRs with 5 or more different βPV types in eyebrow hair had 1.7 times the risk of cSCC vs OTRs with 0 to 4 different types (HR 1.7, 95% confidence interval 1.1- 2.6). A similar risk was seen with high βPV loads (HR 1.8, 95% confidence interval 1.2- 2.8). No significant associations were seen between serum antibodies and cSCC or between βPV and basal cell carcinoma. The diversity and load of βPV types in eyebrow hair are associated with cSCC risk in OTRs, providing evidence that βPV is associated with cSCC carcinogenesis and may present a target for future preventive strategies