Human papillomavirus, high-grade intraepithelial neoplasia and killer immunoglogulin-like receptors: a Western Australian cohort study

Background: Human papillomavirus (HPV) is the causative agent in cervical cancer and HPV genotypes 16 and 18 cause the majority of these cancers. Natural killer (NK) cells destroy virally infected and tumour cells via killer immunoglobulin-like receptors (KIR) that recognize decreased MHC class I expression. These NK cells may contribute to clearance of HPV infected and/or dysplastic cells, however since KIR controls NK cell activity, KIR gene variation may determine outcome of infection.Methods: KIR gene frequencies were compared between 147 patients with a history of high-grade cervical intraepithelial neoplasia (CIN) and a control population of 187, to determine if any KIR genes are associated with high-grade CIN. In addition a comparison was also made between cases of high grade CIN derived from 30 patients infected with HPV 16/18 and 29 patients infected with non-16/18 HPV to determine if KIR variation contributes to the disproportional carcinogenesis derived from HPV 16/18 infection.Results: High-grade CIN was weakly associated with the absence of KIR2DL2 and KIR2DS2 (p = 0.046 and 0.049 respectively, OR 0.6; 95% CI 0.4 – 0.9) but this association was lost after correction for multi-gene statistical analysis.No difference in KIR gene frequencies was found between high-grade CIN caused by HPV 16/18 and non-16/18.Conclusion: No strong association between KIR genes, high-grade CIN and HPV genotype was found in the Western Australian population

Sarcostemma viminale activates macrophages to a pro-inflammatory phenotype

Sarcostemma viminale (L.) R.Br, also known as caustic or milk bush, is a semi-succulent plant commonly found in the North West of Australia. Local Aboriginal populations have long used the milky white sap from this plant to treat skin cancers. An ethanol extract from S. viminale was tested by exposing the RAW264.7 cell line as an in vitro murine macrophage model, to the extract. Flow cytometric analysis was performed to determine if S. viminale skewed macrophages towards a pro-inflammatory or anti-inflammatory phenotype using a number of cell surface markers. Cell culture supernatants were also analysed by cytometric bead array to determine if S. viminale exposed macrophages produced pro-inflammatory or anti-inflammatory cytokines. After exposure to S. viminale, a significantly greater number of macrophages expressed pro-inflammatory major histocompatibility complex (MHC) class II molecules and significantly greater expression levels of the dendritic cell marker CD11c. Cytometric bead array analysis found that S. viminale induced significant amounts of the potent pro-inflammatory cytokine tumour necrosis factor (TNF) from macrophages. The markers CD40 and ICAM-1 were expressed but were not significantly different from the controls. Also, significantly higher expression of CX3CR1 indicated that macrophages were preparing to migrate. No anti-inflammatory cytokines were produced. No significant production of NO2-, IL-6, IFN-? or IL-12 was found. These results demonstrate that S. viminale drives resting macrophages into a pro-inflammatory phenotype, reminiscent of activated immature dendritic cells. If this activation could be achieved in the peri-tumour environment, then S. viminale could be useful as an adjunct therapy for skin cancer. © 2014 Springer-Verlag London

Human papillomavirus predicts outcome in oropharyngeal cancer in patients treated primarily with surgery or radiation therapy

OBJECTIVE: This study examines the prognostic significance of human papillomavirus (HPV) in patients with locally advanced oropharyngeal squamous cell carcinoma (SCC) treated primarily with surgery or definitive radiotherapy. METHODS: One hundred and ninety-eight patients with Stage 3/4 SCC were followed up for recurrence in any form or death from any cause for between 1 and 235 months after diagnosis. HPV status was determined using HPV E6-targeted multiplex real-time PCR/p16 immunohistochemistry. Determinants of recurrence and mortality hazards were modelled using Cox's regression with censoring at follow-up dates. RESULTS: Forty-two per cent of cancers were HPV-positive (87% type 16). HPV predicted loco-regional control, event-free survival and overall survival in multivariable analysis. Within the surgery with adjuvant radiotherapy (n=110), definitive radiotherapy-alone (n=24) and definitive radiotherapy with chemotherapy (n=47) groups, patients with HPV-positive cancers were one-third or less as likely to have loco-regional recurrence, an event or to die of any cause as those with HPV-negative cancers after adjusting for age, gender, tumour grade, AJCC stage and primary site. The 14 patients treated with surgery alone were considered too few for multivariable analysis. CONCLUSION: HPV status predicts better outcome in oropharyngeal cancer treated with surgery plus adjuvant radiotherapy as well as with definitive radiation therapy±chemotherapy

Human Papillomavirus Associated Cancers of the Head and Neck: An Australian Perspective

© 2017, Springer Science+Business Media New York. Human papillomavirus (HPV) associated head and neck squamous cell carcinomas (HNSCCs), have become a serious global health problem. Despite decreases in HPV-negative HNSCCs, the prevalence of HPV-positive HNSCCs has significantly increased. HPV-positive cancers are associated with superior survival outcomes when compared to HPV-negative cancers, which appears likely to be associated with differences in the molecular pathogenesis of the two diseases. While therapies are still problematic, the current HPV vaccine programs hold a promise for the primary prevention of HPV-related HNSCCs and since Australia was the first to introduce a nationwide HPV vaccine program, it is in a unique position to observe the effects of the vaccine on HNSCCs. This review discusses the epidemiological trends associated with HPV in HNSCC, with reference to the differences between HPV-positive and HPV-negative HNSCCs and the prevention potential of HPV vaccines