Tumour Virus Research最新文献

Objective

To assess the concordance of high-risk HPV (HR-HPV) testing with the Alinity assay on cervical samples collected with diverse collection/storage protocols (ThinPrep, SurePath, Cervicollect) and to assess inter-assay concordance of HR-HPV testing of cervical cell specimens with Alinity m HR HPV assay (Alinity) vs cobas® 4800 HPV assay (cobas).

Methods

Specimens were obtained from 560 women attending a Women's Health clinic. Two specimens were obtained from each woman with combinations of two of the three collection devices and aliquots were tested by the two assays.

Results

Alinity showed an agreement of 93.9%, Kappa = 0.89 (263/280) between ThinPrep and SurePath specimens; 97.5%, Kappa = 0.95 (347/356) and 92.9%, Kappa = 0.85 (104/112) between ThinPrep and SurePath aliquots taken before or after cytology processing, respectively. Cervi-Collect specimens showed an agreement of 94.6%, Kappa = 0.89 (265/280) with ThinPrep specimens. Compared to cobas, Alinity showed agreements of 94.3%, Kappa = 0.88 (395/419) and 91.8%, Kappa = 0.82 (257/280) between ThinPrep and SurePath specimens, respectively. Alinity and cobas detected genotypes 16/18 and other high-risk HPV types at similar rates and showed similar correlations with cytology grades.

Conclusions

Compared to cobas, Alinity performed equally well for detecting HPV in cervical specimens obtained with ThinPrep and SurePath. The Cervi-Collect device compared well to the other collection methods. Alinity is a reliable assay for simultaneous detection of HPV-16/18 and other high-risk genotypes in cervical specimens.

Equus caballus papillomavirus type 2 (EcPV2) infection has been associated with genital squamous cell carcinoma (SCC) development in horses. However, very few reports on EcPV2-associated disease in Asia exist. Our study characterizes pathological and virological features of an EcPV2-associated vulvar SCC from a Japanese mare. Conventional PCR, in situ hybridization, reverse-transcriptase PCR and immunohistochemistry confirmed the presence and distribution of EcPV2 within the lesion and suggested that p53 degradation may not be the mechanism by which this virus induces neoplastic transformation. The complete viral sequence in this Japanese case shows near perfect sequence homology with European reference strains of EcPV2, which may be useful when considering the target for future EcPV2 vaccine development. This report also serves to highlight the importance of EcPV2 in female (vulvar) neoplasia, which is less commonly recognized than EcPV2-induced male (penile or preputial) neoplasia. Finally, the SCC described in this mare was an unusual acantholytic variant that has not been reported previously in horses. It is the first report of EcPV2 identified from genital SCC in Asia and underscores the likely worldwide distribution of this virus and its consistent association with equine genital neoplasia.

Background

The multi-dose regimen is a known barrier to successful human papillomavirus (HPV) vaccination. Emerging evidence suggests that one vaccine dose could protect against HPV. While there are clear advantages to a single dose schedule, beliefs about vaccine dosage in low and middle income countries (LMICs) are poorly understood. We investigated acceptability of dose-reduction among girls, and parents/guardians of girls, randomised to receive one, two or three doses in an HPV vaccine dose-reduction and immunobridging study (DoRIS trial) in Tanzania.

Methods

Semi-structured interviews with girls (n = 19), and parents/guardians of girls (n = 18), enrolled in the study and completing their vaccine course.

Results

Most participants said they entrusted decisions about the number of HPV vaccine doses to experts. Random allocation to the different dose groups did not feature highly in the decision to participate in the trial. Given a hypothetical choice, girls generally said they would prefer fewer doses in order to avoid the pain of injections. Parental views were mixed, with most wanting whichever dose was most efficacious. Nonetheless, a few parents equated a higher number of doses with greater protection.

Conclusion

Vaccine trials and programmes will need to employ careful messaging to explain that one dose offers sufficient protection against HPV should emerging evidence from ongoing dose-reduction clinical trials support this.

Epstein-Barr virus (EBV) infects most people worldwide and persists for life due to complicated interplay between lytic infection and multiple types of latent infections. While usually asymptomatic, EBV is a causative agent in several types of cancer and has a strong association with multiple sclerosis. Exactly how EBV promotes these diseases and why they are rare consequences of infection are incompletely understood. Here I will discuss current ideas on disease induction by EBV, including the importance of lytic protein expression in the context of latent infection as well as the possible importance of specific EBV variants in disease induction.

Papillomaviruses, polyomaviruses and adenoviruses are collectively categorized as the small DNA tumour viruses. Notably, human adenoviruses were the first human viruses demonstrated to be able to cause cancer, albeit in non-human animal models. Despite their long history, no human adenovirus is a known causative agent of human cancers, unlike a subset of their more famous cousins, including human papillomaviruses and human Merkel cell polyomavirus. Nevertheless, seminal research using human adenoviruses has been highly informative in understanding the basics of cell cycle control, gene expression, apoptosis and cell differentiation. This review highlights the contributions of human adenovirus research in advancing our knowledge of the molecular basis of cancer.

Background

Human papillomavirus (HPV) infection and related diseases are common among men who have sex with men (MSM). The most effective prevention is HPV vaccination. In China, however, men are not included in the HPV vaccination plan. We investigated the intention to initiate HPV vaccination and associated factors among MSM in China. Methods We surveyed 563 unvaccinated MSM aged 18 or older from six cities in China. Participants completed an electronic questionnaire about demographics, knowledge of and attitude towards HPV and HPV vaccine, intention to initiate HPV vaccination, willingness to recommend HPV vaccine to peers, feeling about government policy about HPV vaccination. We used the structural equation modeling (SEM) to analyze factors associated with HPV vaccine intention. Results The knowledge of HPV and HPV vaccine among participants was low. The mean score of knowledge about HPV and HPV vaccine was only 1.59 (range 0–11). The intention to initiate HPV vaccination within 6 months among participants was moderate (43.3% in total, 18.1% for ‘very high' and 25.2% for ‘above average').

Objective

To develop and evaluate an online continuing education (CE) course designed to improve healthcare provider self-efficacy to make strong adolescent HPV vaccine recommendations to East African immigrant families.

Methods

Focus groups with providers and East African immigrant mothers informed course development. Providers serving East African immigrant families were recruited to view the course and complete pre-/post-test and two-month follow-up surveys. Pre-/post differences were compared with paired t-tests.

Results

202 providers completed the course and pre-/post-test; 158 (78%) completed two-month follow-up. Confidence to make strong HPV vaccine recommendations to East African families increased from 68% pre-test to 98% post-test. Confidence to address common parental concerns also increased: safety, 54% pre-test, 92% post-test; fertility, 55% pre-test, 90% post-test; child too young, 68% pre-test, 92% post-test; and pork gelatin in vaccine manufacturing, 38% pre-test, 90% post-test. Two-month follow-up scores remained high (97% for overall confidence, 94%–97% for addressing parental concerns). All pre-/post-test and pre-test/two-month follow-up comparisons were statistically significant (p < 0.05).

Conclusions

The online CE course focused on culturally appropriate strategies for making strong recommendations and addressing specific parental concerns was effective for increasing provider self-efficacy to recommend HPV vaccination to East African families. Similar courses could be tailored to other priority populations.

In persistent high-risk HPV infection, viral gene expression can trigger some important early changes to immune capabilities which act to protect the lesion from immune attack and subsequently promote its growth and ability for sustained immune escape. This includes immune checkpoint-inhibitor ligand expression (e.g. PD-L1) by tumour or associated immune cells that can block any anti-tumour T-cell effectors. While there are encouraging signs of efficacy for cancer immunotherapies including with immune checkpoint inhibitors, therapeutic vaccines and adoptive cell therapies, overall response and survival rates remain relatively low. HPV oncogene vaccination has shown some useful efficacy in treatment of patients with high-grade lesions but was unable to control later stage cancers. To maximally exploit anti-tumour immune responses, the suppressive factors associated with HPV carcinogenesis must be countered. Importantly, a combination of chemotherapy, reducing immunosuppressive myeloid cells, with therapeutic HPV vaccination significantly improves impact on cancer treatment. Many clinical trials are investigating checkpoint inhibitor treatments in HPV associated cancers but response rates are limited; combination with vaccination is being tested. Further investigation of how chemo- and/or radio-therapy can influence the recovery of effective anti-tumour immunity is warranted. Understanding how to optimally deploy and sequence conventional and immunotherapies is the challenge.

Background

Initially, three-dose schedules were recommended for vaccines against human papillomavirus (HPV); subsequently recommendations have been updated to a schedule of two doses delivered at least six (minimum five) months apart for those aged <15 years at dose 1. We aimed to re-estimate effective HPV vaccination coverage in Australia, considering reduced-dose schedules and possible one-dose effectiveness. We also aimed to identify which of the three school visits was most commonly missed amongst two-dose only recipients, to inform optimal timing of visits.

Methods

National vaccination register data were used to estimate: i) vaccination coverage at December 2017, either with a complete course (three or two sufficiently-spaced doses (>151 days apart)), or at least one dose; ii) for each birth cohort offered vaccination, the percentage of the initially targeted cohort with a complete course, or at least one dose (reflecting uptake at the time the vaccine was offered); and iii) among two-dose only recipients, the percentage who missed each of three school visits.

Results

Including those with two sufficiently-spaced doses increased end-2017 coverage by 1.3–2.8% points in those vaccinated at school. Including those with at least one dose increased coverage further, by 6.5–9.5% points, mostly due to including those receiving multiple too-closely-spaced doses. One-dose coverage reached 90.9% and 86.9% in females and males respectively born in 2002.

Among those vaccinated at school who received only two doses, it was much more common to miss the first (31.0% females; 32.5% males) or the third visit in the school year (54.6% females; 48.6% males) than the second (14.1% females; 18.8% males).

Conclusions

Including those with two sufficiently-spaced doses has a very modest impact on HPV vaccine coverage in Australia. If receiving at least one dose offers substantial protection, these data suggest that the school-based program is now achieving close to 90% coverage on this measure.