Gynaecological Cancers, Head and Neck Cancer, Immunotherapy CE/CME ACCREDITED Watch Time: 34 mins

touchEXPERT OPINIONS HPV infection and TGF-β: Translating the science into treatments for HPV-associated cancers

Watch leading experts review the management of HPV-associated cancers and the biological pathways that are driving the development of new treatments.

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Dr Judith Michels
Institut Gustave Roussy, Villejuif, France
What are the current unmet needs for patients with advanced HPV-associated cancers?

Dr Judith Michels outlines the current treatments and guidelines for HPV-associated cancers, and considers how outcomes for patients with these malignancies may be improved in the future.

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In this interview, Dr Judith Michels answers the following questions:

  • What is the incidence of HPV-associated cancers and how do they vary according to sex?
  • What is the survival rate of patients with advanced HPV-associated cancer?
  • What are the primary treatment options for advanced HPV-associated cancers?
  • What are the associated outcomes of the available treatment options for advanced HPV-associated cancers?
  • How can we improve outcomes for patients with HPV-associated cancers in the future?

Dr Judith Michels is a medical oncologist specializing in gynaecological oncology at the Institut Gustave Roussy in Villejuif, France.
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After completing a combined MD and PhD degree in medical oncology, Dr Michels specialized in gynaecological cancers. Dr Michels has completed a research fellowship at Memorial Sloan Kettering Cancer Center, New York, NY, USA, investigating the effects of P53 stabilization on the tumour immune microenvironment, and how they might enhance the activity of immune checkpoint blockers.

Dr Michels currently develops academic investigator-sponsored trials in ovarian and HPV-related cervical cancers with pioneering immunotherapy combinations.

Dr Judith Michels discloses: Advisory board fees from from GlaxoSmithKline (Relationship Terminated).

 
Dr Andew Sikora
MD Anderson Cancer Center, Houston, TX, USA
What is the link between HPV and TGF-β in HPV-associated cancers?

Dr Andrew Sikora outlines the link between HPV and TGF-β, and how this can drive the development of new therapeutic options for HPV-associated cancer.

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In this interview, Dr Andew Sikora answers the following questions:

  • What are the immune evasion strategies by which HPV establishes persistent infection?
  • What are the primary features of the tumour microenvironment for HPV-positive tumours?
  • What is the dual role played by TGF-β in the tumour microenvironment?
  • What is the impact of TGF-β on immune cells in HPV-associated cancer?
  • How could TGF-β expression affect outcomes in patients with SCCHN?

Dr Andrew Sikora is Professor of head and neck surgery at MD Anderson Cancer Center in Houston, TX, USA. He also serves as Director of Research for head and neck surgery. Dr Sikora’s clinical expertise is in oropharyngeal (throat) cancer and human papillomavirus (HPV)-related head and neck cancer. read more

His research is focused on tumour immunology and cancer immunotherapy. Dr Sikora serves as a member of the National Institute of Health (NIH) National Cancer Institute’s Head and Neck Cancer Steering Committee, the Immuno-Oncology Translational Network (IOTN) Steering Committee and the NRG Cooperative Clinical Trials Group Head and Neck Cancer Core Committee.

Dr Andrew Sikora discloses: Consultancy fees from F. Hoffman La Roche Ltd.

 
Dr Krishnansu Tewari
University of California, Irvine, CA, USA
What therapeutic approaches targeting HPV and TGF-β are being investigated for
HPV-associated cancer?

Dr Krishnansu Tewari summarizes the mechanisms of action and clinical trial data for new and emerging treatment options for patients with HPV-associated cancer.

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In this interview, Dr Krishnansu Tewari answers the following questions:

  • How are immuno-oncology therapies contributing to the treatment of HPV-associated cancers?
  • What are the current data supporting the targeting of TGF-β for the treatment of HPV-associated cancers?
  • What are the ongoing investigations regarding therapeutic vaccines either alone or in combination with other immunotherapeutic agents for treating HPV-associated cancers?
  • What is the potential role of T-cell-based therapies against HPV onco-antigens for the treatment of HPV-induced cancers?
  • What does the future look like for the combination of therapies for the treatment of HPV-associated cancers?

Dr Krishnansu S Tewari, MD, is Full Professor with Tenure and Division Director of the Division of Gynecologic Oncology at the University of California, Irvine, CA, USA. He is also the Director of the Gynecologic Oncology Program at St Joseph’s Center for Cancer Prevention and Treatment in Orange, CA, USA. read more

Dr Tewari is the Chair of the National Cancer Institute’s NRG Oncology Publications Committee, and a voting member of the NRG Oncology Cervical Cancer Committee and NRG Oncology Translational Science/Phase I Committee.

Dr Krishnansu Tewari discloses: Advisory board/panel fees from AbbVie, AstraZeneca, Clovis, Eisai, Genentech, GlaxoSmithKline/Tesaro and Merck (Relationships Terminated). Consultancy fees from AbbVie, AstraZeneca, Clovis, Eisai, Genentech, GlaxoSmithKline/Tesaro and Merck. Grants/research support from AbbVie, AstraZeneca, Clovis, Genentech, Merck and Regeneron. Speaker’s bureau fees from AstraZeneca, Clovis, Eisai and GlaxoSmithKline.

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Overview & Learning Objectives
Overview

In this activity, the expert faculty review the unmet needs for patients with HPV-associated cancers, and the link between HPV and TGF-β, and how this is driving the development of new treatments targeting HPV or TGF-β.

This activity is jointly provided by USF Health and touchIME. read more

Target Audience

This activity has been designed to meet the educational needs of oncologists specializing in the management of gastrointestinal, gynaecological, genitourinary, and head and neck cancers.

Disclosures

All individuals in a position to influence content have disclosed to USF Health any financial relationship with an ineligible organization. USF Health has reviewed and mitigated all relevant financial relationships related to the content of the activity. The relevant relationships are listed below. All individuals not listed have no relevant financial relationships.

Faculty

Dr Judith Michels discloses: Advisory board fees from from GlaxoSmithKline (Relationship Terminated).

Dr Andrew Sikora discloses: Consultancy fees from F. Hoffman La Roche Ltd.

Dr Krishnansu Tewari discloses: Advisory board/panel fees from AbbVie, AstraZeneca, Clovis, Eisai, Genentech, GlaxoSmithKline/Tesaro and Merck (Relationships Terminated). Consultancy fees from AbbVie, AstraZeneca, Clovis, Eisai, Genentech, GlaxoSmithKline/Tesaro and Merck. Grants/research support from AbbVie, AstraZeneca, Clovis, Genentech, Merck and Regeneron. Speaker’s bureau fees from AstraZeneca, Clovis, Eisai and GlaxoSmithKline.

Content Reviewer

Angela Massey Hill, PharmD, CPh, RPh has no financial interests/relationships or affiliations in relation to this activity.

Touch Medical Director

Hannah Fisher has no financial interests/relationships or affiliations in relation to this activity.

USF Health Office of Continuing Professional Development and touchIME staff have no financial interests/relationships or affiliations in relation to this activity.

Requirements for Successful Completion

In order to receive credit for this activity, participants must review the content and complete the post-test and evaluation form. Statements of credit are awarded upon successful completion of the post-test and evaluation form.

If you have questions regarding credit please contact cpdsupport@usf.edu.

Accreditations
Physicians

This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through a joint providership of USF Health and touchIME. USF Health is accredited by the ACCME to provide continuing medical education for physicians.

USF Health designates this enduring material for a maximum of 0.75 AMA PRA Category 1 CreditTM. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

The European Union of Medical Specialists (UEMS) – European Accreditation Council for Continuing Medical Education (EACCME) has an agreement of mutual recognition of continuing medical education (CME) credit with the American Medical Association (AMA). European physicians interested in converting AMA PRA Category 1 CreditTM into European CME credit (ECMEC) should contact the UEMS (www.uems.eu).

Advanced Practice Providers

Physician Assistants may claim a maximum of 0.75 Category 1 credit for completing this activity. NCCPA accepts AMA PRA Category 1 CreditTM from organizations accredited by ACCME or a recognized state medical society.

The AANPCP accepts certificates of participation for educational activities approved for AMA PRA Category 1 CreditTM by ACCME-accredited providers. APRNs who participate will receive a certificate of completion commensurate with the extent of their participation.

Date of original release: 20 January 2022. Date credit expire: 20 January 2023.

If you have any questions regarding credit please contact cpdsupport@usf.edu.

Learning Objectives

After watching this activity, participants should be better able to:

  • Describe the current unmet needs for patients with advanced HPV-associated cancers
  • Recognize the link between HPV infection and TGF-β in HPV-associated cancers
  • Recall the mechanisms of action and latest data for agents targeting HPV or TGF-β for the treatment of HPV-associated cancers
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Question 1/4
In advanced-stage cancer, which of the following is correct regarding the role of TGF-β signalling?

TGF-β, transforming growth factor beta.
Correct

In advanced cancer, TGF-β promotes epithelial-to-mesenchymal transition of cancer cells by restoring mesenchymal phenotypes and upregulating the expression of genes such as Snail and Vim.1

TGF-β, transforming growth factor beta.

Reference

  1. Xue VW, et al. Cancers (Basel). 2020;12:3099.
Question 2/4
In a post hoc pooled analysis of phase I and II studies in patients with immune checkpoint inhibitor-naive, recurrent or metastatic cervical cancer treated with bintrafusp alfa monotherapy, which of the following outcomes was reported?
Correct

The pooled analysis of responses to bintrafusp alfa in patients with heavily pretreated, immune checkpoint inhibitor-naive cervical cancer reported:1

  • Confirmed overall response rate of 28.2% in all patients and 26.5% in patients who received at least a single line of platinum doublet therapy in a non-curative setting
  • Tumour reduction in target lesions in previously irradiated regions
  • Grade ≥3 treatment-related adverse events occurred in 20.5% patients
  • Median overall survival of 13.4 months

Reference

  1. Strauss J, et al. Presented at ASCO Annual Meeting 2021. Abstract 5509.
Question 3/4
Your patient is 50 years of age with a pathologically confirmed diagnosis of metastatic HPV-associated cervical cancer. She has received prior platinum-based chemotherapy. She has a metastasis in the upper lobe of her right lung measuring 2.5 cm, as well as metastases in the hilar and para-aortic lymph nodes. If tumour-infiltrating lymphocyte therapy was an available treatment option for this patient, what would be your first step in the treatment process?
Correct

In tumour-infiltrating lymphocyte therapy, tumour-infiltrating lymphocytes are collected from the tumour during a biopsy or surgical resection, and grown to very large numbers in a laboratory with interleukin-2, a protein that promotes rapid tumour-infiltrating lymphocyte growth, then infused back into the patient.1

Reference

  1. Wang S, et al. BMC Medicine. 2021;19:140.
Question 4/4
Your 63-year-old patient has been diagnosed with oropharyngeal squamous cell carcinoma which has metastasized to the lungs. What do you tell this patient regarding their long-term outcomes?
Correct

Five-year relative survival for oral and oropharyngeal cancer with distant lesions is 40%.1

Reference

  1. ASCO Cancer.Net. Oral and oropharyngeal cancer: Statistics. Available at: www.cancer.net/cancer-types/oral-and-oropharyngeal-cancer/statistics (accessed 15 September 2021).
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