The DNA double strand break repair gene XRCC4, an important caretaker of genome stability, is suggested to play a role in the development of human carcinogenesis. However, no evidence has been provided showing that XRCC4 was associated with oral oncology. In this hospital-based case-control study, the association of XRCC4 G-1394T (rs6869366), intron 3 (rs28360071), intron 7 (rs28360317), and intron 7 (rs1805377) polymorphisms with oral cancer risk in a Taiwanese population was first investigated. In total, 318 patients with oral cancer and 318 age- and gender-matched healthy controls were genotyped. We found a significant different distribution in the frequency of the XRCC4 intron 3 genotype, but not the XRCC4 G-1394T or intron 7 genotypes, between the oral cancer and control groups. Those who had heterozygous del/ins at XRCC4 intron 3 showed a 1.57-fold (95% confidence interval=1.12-2.21) increased risk of oral cancer compared to those with ins/ins. As for XRCC4 G-1394T or intron 7 polymorphisms, there was no difference in the distribution between the oral cancer and control groups. There were significant gene-environment interactions between XRCC4 intron 3 genotype with smoking and with betel quid chewing, but not with alcoholism. In smoker and betel quid chewer groups, the XRCC4 intron 3 del variants exhibited 2.57- and 3.03-fold higher risks than the ins genotype, respectively. Our results firstly suggest that the XRCC4 intron 3 del genotype may be associated with oral oncology and may be a novel useful marker for primary prevention and anticancer intervention.

We studied the distribution of the EBV genome in tumour biopsies obtained from 42 patients with poorly differentiated or undifferentiated nasopharyngeal carcinoma (NPC) and 3 patients with well-differentiated NPC. Six carcinoma in situ (CIS) foci were seen in 5 tumour specimens. By in-situ hybridization, multiple copies of the EBV genome were detected in some of the tumour cells in 3 CIS lesions involving the full thickness of the mucosal epithelium, but without microinvasion, while the viral genome was present in the majority of the tumour cells contained in another 3 CIS lesions with microinvasion. In agreement with previous findings, poorly differentiated and undifferentiated carcinomas regularly carried the viral genome, the number of copies of which was similar to that seen in CIS, while some, but not all, of the tumour cells of the well-differentiated histological type carried the virus. The viral genome was otherwise rarely detected in other areas of the mucosal epithelium and, where present, the viral carriage was confined to a few epithelial cells, in which the viral genome contents were markedly lower than in tumour cells. These results suggest that EBV may first become associated with NPC at an early stage of the disease shortly after the tumour has been initiated.

The relationship of Epstein-Barr virus (EBV), type I human T-cell lymphotropic virus (HTLV-I), and parvovirus B19 to histiocytic necrotizing lymphadenitis was studied prospectively in 10 Taiwanese patients using materials obtained by fine-needle aspiration and lymph node biopsy. The presence of EBV was detected by in situ hybridization for EBV-encoded RNA expression. Immunocytochemistry was used to detect virus-encoded protein for EBV and parvovirus B19. DNA in situ hybridization and polymerase chain reaction were performed to determine the existence of HTLV-I provirus. Expressions of EBV-encoded RNA and Fas ligand were detected in all cases. Expression of EBV-encoded protein was identified in only 1 case. Neither HTLV-I nor parvovirus B19 was detected in any case.

For the development of culturally relevant and effective cessation interventions for betel quid in Taiwan, it is critical to understand and address perceptions of betel quid chewing and barriers to cessation.

BACKGROUND The association of Epstein‐Barr virus (EBV) with Hodgkin's disease (HD) is intimately related to socioeconomic status. The proportion of HD patients with EBV is high in developing countries but low in developed countries. The aim of this study was to delineate the association of EBV with HD in Taiwan. METHODS Tissues from 70 consecutive cases of HD were examined for the presence of EBV, for the latent membrane protein (LMP‐1) by immunohistochemistry, and for EBER‐1 by in situ hybridization. RESULTS There were 53 males and 17 females, with a mean age of 42 years (range, 7‐75 years). Histologic subtypes included nodular sclerosis in 36 cases (51.4%), mixed cellularity in 26 (37.1%), lymphocyte predominance in 6, and lymphocyte depletion in 2. Overall, EBV was expressed in 44 cases (62.9%), with EBER‐1 expression detected in 40 (57.1%) and LMP‐1 detected in 38 (54.3%). The following histologic subtypes were associated with EBV: lymphocyte predominance in 1 of 6 cases (16.7%), nodular sclerosis in 23 of 36 cases (63.9%), mixed cellularity in 18 of 26 cases (69.2%), and lymphocyte depletion in 2 of 2 cases (100%). CONCLUSIONS EBV association with HD is relatively high in Taiwan. Although EBV was detected in all subtypes and at all ages in this study, the low endemic incidence of HD in Taiwan suggests that other factors, besides EBV, play a role in the pathogenesis of HD. Cancer 1998;83:367‐371. © 1998 American Cancer Society.

No abstract

4088 Background: In the randomized, double-blind, phase 3 KEYNOTE-394 trial (NCT03062358), pembro + BSC vs PBO + BSC as 2L therapy significantly reduced the risk of death by 21% (HR 0.79, 95% CI 0.63-0.99, P= 0.0180), prolonged PFS (HR 0.74, 95% CI 0.60-0.92, P= 0.0032), and improved ORR (estimated difference 11.4%, 95% CI 6.7-16.0, P= 0.00004) with a manageable safety profile in pts in Asia with advanced HCC and progression on or intolerance to sorafenib or oxaliplatin-based chemotherapy. Here we present the results of prespecified exploratory HRQoL analyses. Methods: EORTC QLQ-C30 and EuroQol-5D3L (EQ5D-3L) questionnaires were administered at baseline (BL); wks 3, 6, 9, 12, 18; every 9 wks thereafter up to 1 yr or end of treatment; at treatment discontinuation, and at the 30-day safety follow-up visit. Pts who received ≥1 dose of study treatment and completed ≥1 HRQoL assessment were included in the analyses. Least squares mean (LSM) score changes from BL to wk 12 were compared using a constrained longitudinal data analysis model, including treatment by study visit interaction and stratification factors as covariates. Kaplan-Meier method was used to estimate time to deterioration (TTD) (time to 1st onset of ≥10-point decline from BL/confirmed by a 2nd adjacent ≥10-point decline from BL) for EORTC QLQ-C30 global health status (GHS)/QoL. Stratified Cox proportional hazards model was used to assess the magnitude of the treatment difference (HR) between treatment arms in TTD with nominal, one-sided P value calculated. Results: The HRQoL population included 450 pts (298 pembro; 152 PBO). HRQoL compliance rate at wk 12 was 95.7% for pembro for both questionnaires and 94.4% for EORTC QLQ-C30 and 95.3% for EQ5D-3L for PBO. There was a statistically significant difference in LSM for change from BL to wk 12, between the two arms for the QLQ-C30 GHS/QoL score and EQ-5D VAS score, with more decline observed in the PBO arm. Difference in LSM for QLQ-C30 GHS/QoL score between pembro (-3.97; 95% CI, -6.38, -1.56) and PBO (-8.40; 95% CI, -11.71, -5.10) arms was 4.43 (95% CI, 0.47, 8.40; P= 0.0142). Difference in LSM for EQ-5D VAS score between pembro (-2.74; 95% CI, -4.51, -0.96) and PBO (-6.94; 95% CI, -9.40, -4.48) arms was 4.20 (95% CI, 1.21, 7.19; P= 0.0030). GHS/QOL mean scores generally remained stable over time in pembro arm. TTD in EORTC QLQ-C30 GHS/QoL score was similar between arms (HR, 0.85; 95% CI, 0.58, 1.25; P= 0.1993). Conclusions: Over 12 wks, pts treated with PBO + BSC showed more decline in HRQoL than those receiving pembro + BSC. Combined with the efficacy and safety results from KEYNOTE-394, as well as other global 2L trials with pembro, including KEYNOTE-240 and KEYNOTE-224, our data support the benefit of pembro as 2L therapy for pts with advanced HCC. Clinical trial information: NCT03062358.

Background The treatment of recurrent or metastatic head and neck squamous-cell carcinoma (R/M HNSCC) remains challenging. Preclinical studies revealed that B cell depletion could modulate the microenvironment and overcome chemoresistance. We conducted a phase I study to evaluate the feasibility and safety of B cell depletion using the anti-CD20 antibody rituximab to treat HNSCC. Methods Ten patients were enrolled in two protocols. The first four patients treated using protocol 1 received rituximab 1000 mg on days −14 and −7, followed by gemcitabine/cisplatin every 3 weeks, and rituximab was administered every 6 months thereafter. Because of disease hyperprogression, protocol 1 was amended to protocol 2, which consisted of the concomitant administration of rituximab 375 mg/m2 and gemcitabine/cisplatin every 3 weeks. Another six patients were enrolled and treated using protocol 2. Results Three patients treated using protocol 1 exhibited rapid disease progression, and the remaining patient could not undergo evaluation after rituximab treatment. Conversely, no unpredicted harm was observed in the six patients treated using protocol 2. Among these patients, one achieved complete response, and two had partial responses. The disease-free durations in these patients were 7.0, 6.2, and 7.1 months, respectively. Immune cell analysis revealed a higher ratio of cytotoxic T cells to regulatory T cells in responders than in non-responders. Conclusions B cell depletion using rituximab alone in patients with HNSCC can cause hyperprogressive disease. Contrarily, the co-administration of rituximab and cisplatin/gemcitabine was feasible and safe. Trial registration ClinicalTrials.gov Identifier: NCT04361409, 24 April 2020, retrospectively registered