Biomedical subjects

Amanda Tristram

Publications and source records attributed to Amanda Tristram.

5 recordsLinked to original sources

PubMed2006

HPV information needs.

This chapter discusses the importance of providing women with information about human papillomavirus and its role as the causative agent in the development of cervical cancer. Studies assessing current levels of knowledge among the general public are reviewed. What women need to know will be covered, followed by possible strategies for implementation. There are no randomised controlled trials to review regarding information for women about human papillomavirus but a number of well-conducted qualitative studies explore the issues that are faced both by the women undergoing cervical screening and their healthcare providers.

Female↗

PubMed2005

Clinical responses to Cidofovir applied topically to women with high grade vulval intraepithelial neoplasia.

OBJECTIVES: Cidofovir is an acyclic nucleoside phosphonate, with broad spectrum anti-viral activity. It has previously been used in a number of clinical settings, including high grade intraepithelial disease in the cervix and low grade vulval disease. This pilot study was set up to assess whether Cidofovir might be useful in treating high grade vulval intraepithelial neoplasia. METHODS: Women with high grade non-cervical anogenital intraepithelial neoplasia were treated with a topical formulation of 1% Cidofovir in Unguentum Merck. Safety, side effects, clinical response and viral status were assessed. Clinical response was measured using symptoms, clinical (and photographic) appearance, viral status and histology. RESULTS: 12 women with high grade vulval, vaginal or perianal intraepithelial neoplasia were recruited, 10 of whom completed follow up. Diseased tissue underwent ulceration in the majority of cases, with no effect seen on neighbouring normal skin. Four women had complete regression of disease, with resolution of long standing symptoms as well as histological and viral clearance. Three women had a partial response. Two women did not respond, and one woman made a complete symptomatic response but was found to have invasive disease at final biopsy. CONCLUSION: These complete responses, in women with long standing disease, together with preservation of normal tissue, suggest that topical treatment with Cidofovir may have a place in the therapeutic armamentarium of high grade vulval intraepithelial neoplasia.

Administration, Topical↗

PubMed2004

Epitope specificity and longevity of a vaccine-induced human T cell response against HPV18.

Persistent human papillomavirus (HPV) type 16 and 18 infection can lead to pre-malignant and malignant diseases of the lower genital tract. Several lines of evidence suggest that T cell responses can control HPV infection. However, relative to other human viruses, strong effector memory T cell responses against HPV have been difficult to detect. We used an in vitro stimulation step prior to enzyme-linked immunospot assays to identify IFN-gamma-secreting T cells specific for HPV16 and 18 E6/E7 peptides. This allowed the detection of HPV-specific CD4+ T cells that were not evident in direct ex vivo assays. T cell responses against HPV16 or 18 peptides were detected in healthy volunteers (7/9) and patients with lower genital tract neoplasia (10/20). Importantly, this assay allowed tracking of vaccine-induced T cell responses in nine patients, following inoculation with a live recombinant vaccinia virus (HPV16 and 18 E6/E7, TA-HPV). Novel vaccine-induced T cell responses were demonstrated in five patients, but no clinical responses (lesion regressions) were seen. For one vaccinated patient, the T cell response was mapped to a single dominant HPV18 E7 epitope and this response was sustained for >3 years. Our data suggest that systemic memory T cells against HPV16 and 18, induced naturally or by TA-HPV vaccination, are relatively rare. Nevertheless, the assay system developed allowed estimation of magnitude, epitope specificity, and longevity of vaccine-induced CD4+ T cell responses. This will be useful for vaccine design and measurement of immunological endpoints in clinical trials.

Adult↗

PubMed2004

Immunological responses in women with human papillomavirus type 16 (HPV-16)-associated anogenital intraepithelial neoplasia induced by heterologous prime-boost HPV-16 oncogene vaccination.

PURPOSE: The purpose is to study the immunogenicity of heterologous prime-boost human papillomavirus (HPV) oncogene vaccination in patients with anogenital intraepithelial neoplasia (AGIN). EXPERIMENTAL DESIGN: Twenty-nine women with high-grade AGIN received three i.m. doses of TA-CIN (HPV-16 L2/E6/E7 protein) at four weekly intervals followed by a single dermal scarification of vaccinia HPV-16/18 E6/E7 and were followed up for 12 weeks. Immunity to HPV-16 was assessed by lymphoproliferation, IFN-gamma enzyme-linked immunospot (ELISPOT), and ELISA. RESULTS: The patient group significantly responded to TA-CIN and not to the control antigen HPV-6 L2/E7 at all postvaccination time points when compared with baseline responses (P < or = 0.05). Ten of the patients showed at least a 3-fold increase in TA-CIN-specific proliferation at one or more time points after vaccination. Comparison of stimulation with HPV-16 E6- or E7-GST fusion proteins showed that proliferative responses were biased to HPV-16 E6. This bias was also seen by IFN-gamma ELISPOT using overlapping peptides, with HPV-16 E6- or E7-specific T cells being detected in 9 and 2 patients, respectively. In addition, vaccination resulted in the induction of antibodies against the HPV-16 oncoproteins. Of the 6 clinical responders, 2 patients showed both a proliferative TA-CIN-specific response and an E6-specific IFN-gamma response, whereas 3 other patients displayed E6-specific reactivity only. Stable disease was recorded in 19 patients, 8 of whom showed a concomitant TA-CIN-specific proliferative and/or E6-specific T-cell response. Of the 4 progressors, 2 failed to make a T-cell response and 2 responded by either proliferation or E6 ELISPOT alone. CONCLUSIONS: The prime-boost regimen is immunogenic in AGIN patients (humoral and cellular immunity), but there is no simple relationship between induction of systemic HPV-16-specific immunity and clinical outcome. Other factors that may play a role in the eradication of long-term established AGIN lesions need to be determined to identify the patient group that would benefit from immunotherapy with the vaccines used in this study.

Antibodies, Viral↗

PubMed2004

Vaccination against cervical cancer.

The link between human papillomavirus (HPV) and cervical cancer raises the question, can the burden of cervical cancer be reduced using HPV vaccination strategies? The clinical trials to date will be reviewed, along with the challenges and potential for future development.

Antibody Formation↗