Effect of electrochemotherapy on human herpesvirus 8 kinetics in classic Kaposi sarcoma

Abstract

BackgroundElectrochemotherapy (ECT) has shown to be an effective treatment for cutaneous and subcutaneous Kaposi sarcoma (KS) lesions. However, no study has investigated the impact of ECT treatment on the kinetics of human herpesvirus type 8 (HHV8), which is considered the necessary causal agent of KS. We aimed to evaluate HHV8 viral load and expression levels in patients affected by classic KS who received one or more ECT treatments and have been followed semi annually for up to four years.MethodsA total of 27 classic KS patients were enrolled in this study. Tumour biopsies and blood samples were obtained before ECT treatment. Additional blood samples were collected at six month intervals for 12–48 months. HHV8 viral load and expression profiles of latent (ORF72 and ORF73) and lytic (K2, K8, K8.1, K10/K10.1, K10.5/K10.6 and ORF16) genes were assessed in all samples by real-time PCR. HHV8 ORF26 and K1 regions were amplified and subjected to direct nucleotide sequencing followed by phylogenetic analysis for variant identification.ResultsAll KS biopsies and 46.4% of peripheral blood mononuclear cells (PBMCs) collected before ECT treatment were positive for HHV8 DNA. Viral load ranged from 0.02 to 2.3 copies per cell in KS lesions and 3.0 × 10−7 to 6.9 × 10−4 copies per cell in PBMCs. Overall, latent ORF72 and ORF73 as well as lytic K2, K8 and K10/K10.1 were expressed in all KS biopsies. ORF16 mRNA was detected in 71.4% and both K8.1 and K10.5/K10.6 mRNAs in 57.1% of KS samples. The ORF72, ORF73 and K2 transcripts were amplified in 37.5%, 25% and 25% of PBMCs collected before ECT, respectively. After the first ECT session, complete response was achieved in 20 out of 27 (74.1%) patients and HHV8 DNA was detected in four out of 27 (14.8%) PBMC samples at six month follow up. Phylogenetic analysis of ORF26 amplimers showed that most viral variants belonged to A/C (82.3%), and few to C2 (5.9%) or C3 (11.8%) subtype. The K1/VR1 variants fell into A (33.3%) and C (66.7%) HHV8 clade. No correlation was found between HHV8 subtypes and ECT complete response.ConclusionsECT therapy has a significant effect on HHV8 kinetics in patients with classic KS. The complete remission of patients was accompanied by clearance of circulating virus.

Electrochemotherapy in Kaposi sarcoma: A systematic review

“…Patients with stable or progressive disease were not reported. The reported CR rate after a single ECT session was 60.9% as reported by Curatolo et al (11) and 74.1% in the study by Starita et al (13). Moreover, Latini et al (12) reported 88.9% CR rate after the first ECT session.…”

“…Five full texts were examined following screening of the titles and abstracts. Following assessment of the latter, three studies were included in the analysis (11)(12)(13). One record, which was a letter to the editor, was excluded and the secondary title partially reported on patients was subsequently included in another study from the same centre.…”

“…The median follow-up was reported in only one series (18 months) (11). Previous treatments were not reported in one study (13). However, Curatolo et al (11) described previous local or systemic treatments as follows: Systemic chemotherapy (26.1%), radiotherapy (21.7%), intralesional chemotherapy (4.3%) and interferon (13.0%).…”

“…In both series, the viral load and viral blood titre correlated with ECT response. More specifically, the levels of the viral-related parameters declined markedly in patients with complete response (CR) (12,13).…”

Electrochemotherapy of superficial tumors – Current status:

“…Clinical experience is sparse [212][213][214][215][216][217][218][219][220][221][222] . However, small tumor size, superficial location, and prominent vascularization make Kaposi's sarcoma an ideal target for ECT, by allowing its antivascular effect to be exploited [47] .…”