HPV Cancer Resources

Approximately 13 to 36 percent of HPV+ head and neck cancer patients will develop either recurrences at the original site, or metastasis (i.e. spread) of their cancers to a distant site. Unfortunately, this puts them at much greater risk of dying from their HPV cancers.
Reder et al Mutation patterns in recurrent and/or metastatic oropharyngeal squamous cell carcinomas in relation to human papillomavirus status. Cancer Medicine. 2021;00:1–10.
Faraji et al Emerging Insights Into Recurrent and Metastatic Human Papillomavirus-Related Oropharyngeal Squamous Cell Carcinoma. Laryngoscope Investigative Otolaryngology 2: February 2017
DOI: 10.1002/lio2.37

This page is for those who have experienced either recurrent or metastatic disease (i.e. cancer that has spread to other organs). In the case of HPV+ head and neck cancers, about 5 to 10% of patients are not successfully treated with standard surgery and/or chemotherapy/radiation treatments. Either the cancer reappears in the head and neck regions, or it is found in other organs. Although the lung is the most common distant site involved in both HPV+ and HPV- disease, the HPV+ patients get metastases to several locations that are atypical for head and neck squamous cell carcinoma, including the brain, kidney, skin, skeletal muscle, axillary lymph nodes, and the intra-abdominal lymph nodes.

Here’s a short video from the National Cancer Institute explaining how cancer metastasis works:

Surgery, chemotherapy, and radiation treatments of various types are the current standard of care for treating HPV+ head and neck cancers. If your cancer returns in the treatment area, it may not be possible to treat it again with chemotherapy and/or radiation because your body may not be able to withstand such harsh treatment (e.g. radiation) a second time. If this happens, your doctor may decide that you are a good candidate for an immunotherapy treatment. Several of these have been approved by the FDA for HPV+ head and neck cancer patients. However, only a subset of patients will actually be offered this treatment option following examination of their cancer cells for the presence or absence of specific proteins on these cells. If you don’t have these proteins on your cancer cells, the treatments will not work for you.

The monoclonal antibodies anti-programmed death protein-1 (anti–PD-1) nivolumab (Opdivo) and pembrolizumab (Keytruda) are the first immune checkpoint inhibitors (ICIs) approved for the treatment of recurrent or metastatic HPV+ head and neck cancers. How do these drugs work? These immunotherapeutic agents act by enhancing your immune system’s ability to attack your cancer cells by blocking suppressive signals on the cancer cells through what is referred to as the PD-1/PD-L1 pathway. These drugs can work for some period of time to either shrink your cancer, or to keep it from growing. However, data from clinical trials that investigated the use of these ICI drugs in treating HPV+ head and neck cancers showed that only a relatively small subset of patients really benefit from this treatment, underlining the crucial role of patients’ selection before starting immunotherapy.

Below is an excellent video from the National Cancer Institute that nicely explains how these drugs work:

If conventional treatments are not appropriate for treating cancer patients (or if they don’t work), then a clinical trial of a new treatment is often the next step. The good news is that there are a lot of them available for head and neck cancer patients. Most of them should be available to those who have HPV+ head and neck cancers. The graphic below, though complicated, should give you (or your doctors) a feel for the many different types of trials that are being tested. The reason that there are so many trials going now is because of both commercial and medical issues. There’s been a huge push into immunotherapy treatments over the past few years as certain treatments, such as the checkpoint inhibitors mentioned above (e.g. Keytruda; Opdivo), have gone mainstream. Many different immunotherapy approaches are being tried, and there is simply no way to know, in advance of doing the trials, which ones are most likely to work. Clinical evidence will emerge slowly as the trials are completed and the results are carefully analyzed. This may take a considerable period of time since the ultimate measure of success is long term patient survival.

Check out the Clinical Trial Basics page to get a good understanding of how these trials are done.

The Head and Neck Cancer Alliance has a search tool on it’s website for finding clinical trials that may be of help for head and neck cancer patients. These include trials for HPV+ as well as HPV- cancers.

You can also check out the Trialjectory website to see if there are any clinical trials for which you may be eligible. It’s not clear exactly which resources this website uses to locate trials; it may or may not be limited to sponsors who pay to have their trials listed there.

The widest list of clinical trials should be found on the government run website clinicaltrials.gov

You might also ask your doctor if a clinical trial focused on HPV-caused cancers in other tissues (e.g. cervical cancer) might be a possible fit for you if the target of the trial is HPV itself.

There are currently more than 200 immunotherapy trials being done with head and neck cancer patients. You will have to discuss with your doctors which trials you might be eligible for. Some may require you to relocate to a distant city to participate. Look at my Clinical Trial Basics page for more general information about how clinical trials are done. The list below should NOT be considered comprehensive, and trials can start and stop at any time.

One area that I want to focus on is clinical trials that are specifically targeting the HPV virus itself. The idea is that if HPV is responsible for causing the cancer, then attacking HPV DNA or proteins in cells might have a good chance of knocking the cancer out. Let me be absolutely clear about one thing: attacking HPV as the target may or may not be more successful than any of the other types of treatment approaches depicted in the graphic above. There is simply no way to know this. One possible advantage for the cancer field in general of these HPV targeted treatments is that they may, IF they are successful, be useful for treating ALL of the HPV-caused cancers. Thus, they may work in treating cervical, vaginal, vulval, penile, and anal cancers in addition to working on HPV+ head and neck cancers. The list below shows some of these treatments being targeted against head and neck cancers, along with some other targets in these same cancers. Keep in mind that there are other HPV-focused clinical trials that are being conducted on other cancers (e.g. cervical cancer) and do not appear in the table below. Again, if one of these treatments is successful against cervical or one of the other HPV-caused cancers, then there is a reasonable chance that it would have some efficacy against HPV+ head and neck cancers as well. These types of treatments are often referred to by doctors as being pan-specific or tissue agnostic. That’s just a fancy way of saying that they should work in any tumor that’s caused by HPV. Sounds good, right? One treatment for six cancers. Who wouldn’t want that to work?

Here's a link to an article from Oct. 2024 illustrating the different approaches being taken at developing therapeutic anti-cancer vaccines specifically focused on proteins made by HPV. Some of these appear to be promising, but we will need to see data from clinical studies before we know which ones will really work in people. If you have metastatic disease, please ask your medical team the possibility of participating in a clinical trial using one of these approaches. Do not give up hope!

Demidova, A. et al Comparison of preclinical efficacy of immunotherapies against HPV-induced cancers. Expert Review of Vaccines 2024, VOL. 23, NO. 1, 674–687. https://doi.org/10.1080/14760584.2024.2374287

Here's a promotional description of a newly started clinical trial in 2024 using a lentiviral vector targeting HPV in head and neck as well as cervical cancer. Put another way, this is a therapeutic vaccine trial.
Human Papillomavirus (HPV)-induced Cancers: First Patient Enrolled in Phase I/IIa Clinical Trial for Lenti-HPV-07, the TheraVectys’ Therapeutic Vaccine Candidate Against Oropharyngeal and Cervical Cancers

Here’s a link to an article about the combination of therapeutic HPV vaccines (i.e. directed against the E6 and/or E7 proteins made by HPV) in combination with PD-1or PD-L1 immunotherapy drugs. These latter drugs that target PD-1 or PD-L1 are known as checkpoint inhibitors, and some of them have had some success on their own treating metastatic disease.

Here's an article that explains how HPV caused cancers can evade your immune system, and how it may be possible to overcome that.
Ge, J. et al. Human papillomavirus-encoded circular RNA circE7 promotes immune evasion in head and neck squamous cell carcinoma. Nature Communications volume 15, Article number: 8609 (2024)

Below are descriptions of some clinical trials (not necessarily currently focused on head and neck cancers) that are specifically targeting HPV. This list may be out of date, and any particular trial may have been completed (or abandoned) by the time you read this. The best way to confirm that is to go to the ClinicalTrials.gov website and used the identifier number for the trial to find out the current status. Note that this database is not always up to date either, so if you see a trial of interest, have your doctor contact the clinical coordinator listed on the ClinicalTrials.gov trial page. Even if these trials are no longer accepting patients, they may be about to open up for patients with similar cancers. That’s why it’s valuable to look at trials for cervical or anal cancer, for example. Success in those clinical trials with an agent targeting HPV may result in expansion to other tissues e.g. head and neck cancers.

Keep in mind that there are many more general clinical trials ongoing for head and neck cancers, that is, they are open to people who’s cancers are HPV positive or negative. These trials may be every bit as effective (or, sadly, ineffective) as those that specifically target HPV. Put another way, don’t ignore clinical trials just because they are not focused on HPV positive head and neck cancers. We don’t know yet that the HPV targeting trials will be more effective than those that don’t specifically target HPV.

This section is intended to give a feel for clinical trials in this area. It is NOT intended to be a complete list. Your doctor should be able to direct you to other clinical trials, or you can look them up yourself on clinical trials.gov:
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ClinicalTrials.gov identifier: NCT03912831

FOCUS OF THE THERAPY: CAR-T immunotherapy directed against the E7 protein of HPV. CAR-T trials have shown remarkable success in other indications (e.g. lymphoma) but have also been associated with very serious side effects.

HOW IT WORKS: Your blood is drawn and the T cells in that blood are purified. They are then genetically modified to target them against a protein made by HPV. The T cells are supposed to kill off all of the HPV infected cells, thereby eliminating the cancer. The exact protocol features cyclophosphamide plus fludarabine chemo followed by KITE-439 (targets the E7 encoded protein of HPV) in HLA-A*02:01 adults.

DISEASE TARGETED: Relapsed/refractory HPV 16+ cancers, type not specified

WHERE BEING CONDUCTED: City of Hope Medical Center, Duarte, CA; H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, and University of Chicago Medical Center.

TRIAL STATUS (as of 2019): Recruiting

TRIAL SPONSOR: Kite Pharmaceuticals (Gilead)
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ClinicalTrials.gov identifier: NCT05357898

FOCUS OF THE THERAPY: A Phase 1/2, First-in-Human, Multicenter, Open-Label Study of SQZ-eAPC-HPV as Monotherapy and in Combination With Immune Checkpoint Inhibitor(s) in Patients With HPV16+ Recurrent, Locally Advanced, or Metastatic Solid Tumors

HOW IT WORKS: In this new therapy, researchers take a persons blood, remove certain white blood cells, and squeeze them to open up pores on the cells. The cells are then exposed to proteins from the HPV virus, which is supposed to stimulate the immune cells in the blood to attack cancer cells expressing HPV proteins. n. The modified cells are then given back to the person to fight the cancer. Researchers want to see if this can help people. In a separate group, patients will get the squeezed cells along with pembrolizumab, a checkpoint inhibitor, to see if the combination works better.

DISEASE TARGETED: Relapsed/refractory HPV 16+ cancers, type not specified

WHERE BEING CONDUCTED: Multiple sites in the US, including Nashville, TN; Cincinnati, OH; Boston, MA; Aurora, CO, and Scottsdale, AZ.

TRIAL STATUS (as of 2023): Recruiting

TRIAL SPONSOR: SQZ Biotechnologies

Reference: Micro-fluidic squeezing technology can treat head, neck cancer: Research

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ClinicalTrials.gov identifier: NCT02858310

FOCUS OF THE THERAPY: In this new therapy, researchers take a person s blood, remove certain white blood cells, and insert genes that make them to target cancer cells that have the E7 protein. The genetically changed cells, called E7 TCR cells, are then given back to the person to fight the cancer. Researchers want to see if this can help people.

HOW IT WORKS: Your blood is drawn and the T cells in that blood are purified. They are then genetically modified to target them against a protein made by HPV. The T cells are supposed to kill off all of the HPV infected cells, thereby eliminating the cancer. Patients must be HLA-A*02:01 positive adults.

DISEASE TARGETED: Relapsed/refractory HPV 16+ cancers, type not specified

WHERE BEING CONDUCTED: Multiple sites in the US, including Birmingham, AL; Gilbert, AZ; Los Angeles, CA; Miami, FL; Chicago, IL; Fairway, KS; Detroit, MI; St. Louis, MO; NY, NY; Bronx, NY; Oklahoma City, OK; Portland, OR; Greenville, SC; Oklahoma City, OK; Houston, TX; and Milwaukee; WI.

TRIAL STATUS (as of 2021): Recruiting

TRIAL SPONSOR: NIH

Reference: Nagarsheth et al TCR-engineered T cells targeting E7 for patients with metastatic HPV epithelial cancers. Nature Medicine Feb 8, 2021.
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ClinicalTrials.gov identifier: NCT04015336

FOCUS OF THE THERAPY: The purpose of this study is to determine if E7 TCR T cells can be given safely without delaying standard treatment for HPV-16 associated oropharyngeal cancer. Standard treatment may be surgery or radiation therapy with chemotherapy.

HOW IT WORKS: Participants will have a large IV catheter inserted into a vein to undergo a procedure called leukapheresis. Leukapheresis is the removal of the blood by a machine to collect specific blood cells. The remaining blood is returned to the body. This procedure is needed to collect the cells that will be modified to target the cancer. These cells will be grown in the lab and given back to the participant through an IV. It takes 11-15 days to grow the cells.
While the cells are growing, the participant will be admitted to the hospital about one week before cell infusion. They will receive 2 types of chemotherapy through an IV catheter over 5 days. The main purpose of the chemotherapy is to make the cells more effective in fighting the cancer tumors. The cells will be given through an IV catheter 1-3 days after the last dose of chemotherapy. Within 24 hours after the cell infusion, participants will be given a cell growth factor called aldesleukin through an IV. Aldesleukin is thought to help the cells live longer in the participant s body. Participants will recover in the hospital until they are well enough to go home. This is usually about 7-12 days after the cell infusion or last dose of aldesleukin. Participants will have follow-up visits starting every 2 weeks after the date of cell infusion. These will be visits to monitor the safety of the treatment and to evaluate the response of the cancer to the treatment. These visits will continue if the cancer is shrinking. The participant will go back to their local cancer doctor for further care if the cancer stops shrinking, goes away completely or gets bigger.

DISEASE TARGETED: Relapsed/refractory HPV 16+ cancers

WHERE BEING CONDUCTED: National Institutes of Health Clinical Center, Bethesda, MD

TRIAL STATUS (as of 2019): Recruiting

TRIAL SPONSOR: NIH

Norberg S. et al. Safety and clinical activity of gene-engineered T-cell therapy targeting HPV-16 E7 for epithelial cancers. J Clin Oncol. 2020;38(suppl 15):101. doi: 10.1200/JCO.2020.38.15_suppl.101
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ClinicalTrials.gov identifier: NCT01022346

FOCUS OF THE THERAPY: Immunotherapy: Infuses a protein that activates an immune system response to combat high-risk HPV lesions.

HOW IT WORKS: The modified vaccinia virus Ankara (MVA) is a highly attenuated replication-deficient strain of vaccinia virus used widely as a gene-delivery system of vaccines. Tipapkinogen Sovacivec (TS) has inserted genes that code for three proteins: human cytokine IL-2, and modified forms of HPV 16 E6 and E7 proteins that have been rendered non oncogenic. MVA by itself contributes to the immune reaction by the induction of an Interferon-alpha response. Upon sub-cutaneous injection, TS infects the surrounding cells. The expressed HPV16 E6 and E7 proteins are then processed and presented by dendritic cells that are co-activated by the viral infection. These dendritic cells migrate to the draining lymph-node and present E6 and E7 peptides to the naive T-cells present in the lymph-node, which should allow development of a targeted cell mediated immune response.

DISEASE TARGETED: High Grade Cervical Intraepithelial Neoplasia Grade 2 or 3 Associated With High Risk HPV Infection

WHERE BEING CONDUCTED: 66 locations

TRIAL SPONSOR: Hoffmann-La Roche

TRIAL STATUS (as of 2019): Completed

REFERENCE: Harper, D.M. et al. The efficacy and safety of Tipapkinogen Sovacivec therapeutic HPV vaccine in cervical intraepithelial neoplasia grades 2 and 3: Randomized controlled phase II trial with 2.5 years of follow-up. Gynecologic Oncology 153, 521-529 (2019). FREE Download
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ClinicalTrials.gov identifier: NCT03721978

FOCUS OF THE THERAPY: Immunotherapy: Infuses a protein that activates an immune system response to combat high-risk HPV lesions.

HOW IT WORKS: VGX-3100 is a DNA-based immunotherapy under investigation for the treatment of HPV 16 and HPV 18 infection and pre-cancerous lesions of the cervix (Phase 3) and vulva and anus (Phase 2). VGX-3100 has the potential to be the first approved treatment for HPV infection of the cervix and the first non-surgical treatment for precancerous cervical lesions. VGX-3100 works by stimulating a specific immune response to HPV-16 and HPV-18, which targets the infection and causes destruction of precancerous cells. In a randomized, double-blind, placebo-controlled Phase 2b study in 167 adult women with histologically documented HPV 16/18 cervical HSIL (CIN2/3), treatment with VGX-3100 resulted in a statistically significantly greater decrease in cervical HSIL and clearance of HPV infection vs. placebo. The most common side effect was injection site pain, and no serious adverse events were reported. VGX-3100 utilizes the patient's own immune system to clear HPV 16 and HPV 18 infection and precancerous lesions without the increased risks associated with surgery, such as loss of reproductive health and negative psychosocial impacts.

AGENTS USED: VGX-3100, a synthetic vaccine designed to raise immune responses against the E6 and E7 oncogenes associated with HPV types 16 and 18, i.e., it targets four antigens. These oncogenes are responsible for transforming HPV-infected cells into precancerous and cancerous cells. The goal is to stimulate a T-cell immune response strong enough to cause the rejection of these infected or transformed cells. The potential of such a therapeutic vaccine would be to treat precancerous dysplasias (cervical intraepithelial neoplasias or CINs), cervical cancers, as well as other cancers caused by these HPV types such as head and neck and anogenital cancers.

DISEASE TARGETED: Cervical cancer precursor

WHERE BEING CONDUCTED: Ten sites in the US

TRIAL STATUS (as of 2019): Recruiting

TRIAL SPONSOR: Inovio Pharmaceuticals, Inc.
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ClinicalTrials.gov identifier: NCT02411019

FOCUS OF THE THERAPY: This is a follow-up study to investigate the change of immunogenicity and lesion condition in subjects with cervical intraepithelial neoplasia (CIN) 3 who have enrolled and participated GX-188E phase II trial (GX-188E_CIN3_P2).

HOW IT WORKS: In phase II study, 72 patients were assigned to two dose groups (1mg and 4mg) and were administered three times with GX-188E by electroporation during an entire period of study. After the final administration, the follow-up will be conducted to investigate safety and efficacy aspects.

AGENTS USED: GX-188E, a synthetic vaccine. Details about the vaccine are murky. The potential of such a therapeutic vaccine would be to treat precancerous dysplasias (cervical intraepithelial neoplasias or CINs), cervical cancers, as well as other cancers caused by these HPV types such as head and neck and anogenital cancers. Results from a phase II study have been presented.

DISEASE TARGETED: Cervical cancer precursor

WHERE BEING CONDUCTED: Several sites in Korea

TRIAL STATUS (as of 2019): Recruiting

TRIAL SPONSOR: Genexine, a Korean biotechnology company
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ClinicalTrials.gov identifier: NCT03057912

FOCUS OF THE THERAPY: A Safety and Efficacy Study of TALEN and CRISPR/Cas9 in the Treatment of HPV-related Cervical Intraepithelial Neoplasia

HOW IT WORKS: HPV persistent infection is the major causal factor of cervical intraepithelial neoplasia (CIN) and cervical cancer. The important roles of E6 and E7 playing in HPV-driven carcinogenesis make them attractive targets for therapeutic interventions. Previous evidences showed that using designated TALEN and CRISPR/Cas9 as genome editing tool could produce disruption of HPV16 and HPV18 E6/E7 DNA, significantly decreasing the expression of E6/E7, inducing cell apoptosis and inhibiting cell lines growth.
This study will evaluate the safety and efficacy of TALEN-HPV E6/E7 and CRISPR/Cas9-HPV E6/E7 in treating HPV Persistency and HPV-related Cervical Intraepithelial Neoplasia

AGENTS USED: Gene modifying therapies TALEN and CRISPR

WHERE BEING CONDUCTED: The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China

TRIAL STATUS (as of 2019): Not yet recruiting

TRIAL SPONSOR: Hu Zheng, First Affiliated Hospital, Sun Yat-Sen University
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ClinicalTrials.gov identifier: NCT03162224

FOCUS OF THE THERAPY: Combination immunotherapy

HOW IT WORKS: MEDI0457 (previously called INO-3112) is an investigational immunotherapy being developed to treat human papillomavirus (HPV)-positive cervical cancer and head and neck cancer. It was originally developed by Inovio, but MedImmune, which is part of AstraZeneca, acquired exclusive rights to the drug in August 2015. MEDI0457 is a DNA-based cancer vaccine with two main components produced using Inovio’s proprietary SynCon technology. Those components are VGX-3100, a DNA plasmid containing modified sequences for E6 and E7, and INO-9012, a DNA plasmid containing the immune activator IL-12. Plasmids are pieces of circular DNA that contain the sequences necessary to promote the expression of a certain gene.
MEDI0457 is injected into the patient’s muscle and enters the cells after electroporation treatment carried out by Inovio’s Cellectra delivery device. Electroporation is the application of a small electrical pulse. When E6 and E7 are expressed from VGX-3100, the immune system recognizes these proteins as antigens, or foreign substances associated with an infection or disease. This triggers the production of cytotoxic T lymphocytes (CTLs), or “killer” T-cells. CTLs are a type of immune cell that can identify and destroy cells expressing a particular antigen, in this case, the HPV-infected tumor cells. The expression of IL-12 will boost the immune response produced by VGX-3100 as it stimulates the production of CTLs, increasing the potential for tumor cell death.

AGENTS USED: MEDIO457 (also known as INO 3112), an HPV DNA vaccine, plus checkpoint inhibitor durvalumab (mAb against PL-L1). MEDI0457 administration by IM injection followed by electroporation (EP) using CELLECTRA®5P device.

DISEASE TARGETED: Head and neck cancer

WHERE BEING CONDUCTED: 23 locations

TRIAL STATUS (as of 2019): Active, not recruiting

TRIAL SPONSOR: MedImmune
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ClinicalTrials.gov identifier: NCT03578406

FOCUS OF THE THERAPY: Two-Arm Open-Labeled Trial of HPV-E6-Specific TCR-T Cells With or Without Anti-PD1 Auto-secreted Element in the Treatment of HPV-Positive Head and Neck Carcinoma or Cervical Cancer

HOW IT WORKS: T cell therapy administered with or without a PD-1 (checkpoint) inhibitor

AGENTS USED: Patients were infused with HPV E6-specific TCR-T cells

DISEASE TARGETED: Head and neck cancer; cervical cancer

WHERE BEING CONDUCTED: Chongqing , China

TRIAL STATUS (as of 2019): Not specified

TRIAL SPONSOR: Xinqiao Hospital of Chongqing, TCRCure Biotech Co., Ltd
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ClinicalTrials.gov identifier: NCT04180215

FOCUS OF THE THERAPY: Phase 1/2 clinical trial of HB-201, an immunotherapy for the treatment of Human Papillomavirus 16-positive (HPV16+) cancers. HB-201 is an arenavirus vector-based vaccine expressing the inactivated fusion protein HPV 16 E7E6. This is a first in human (FIH) Phase I/II, multinational, multicenter, open-label study of HB-201 monotherapy or in combination with an immune checkpoint inhibitor in HPV 16+ confirmed cancers that consists of 2 parts: Phase I Dose Escalation and Phase II Dose Expansion.

HB-201 is a TheraT® platform-based vector (replication attenuated) from the arenavirus family expressing a non-oncogenic, but highly antigenic E6/E7 fusion protein from HPV16.

HOW IT WORKS: Induces T cell anti-tumor responses

AGENTS USED: HB-201, an immunotherapy for the treatment of Human Papillomavirus 16-positive (HPV16+) cancers.

DISEASE TARGETED: HPV+ advanced, metastatic, or recurrent head and neck cancer; other HPV+ cancers

WHERE BEING CONDUCTED: Not specified

TRIAL STATUS (as of 2019): Phase 1/2 clinical trial started Dec. 30, 2019

TRIAL SPONSOR: HOOKIPA Biotech of Austria. Principal Investigator is Igor Matushansky, MD, PhD
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ClinicalTrials.gov identifier: NCT02865135

FOCUS OF THE THERAPY: A Phase Ib/II Trial To Test The Safety And Efficacy Of Vaccination With HPV16-E711-19 Nanomer For The Treatment Of Incurable HPV 16-Related Oropharyngeal, Cervical And Anal Cancer In HLA-A*02 Positive Patients

HOW IT WORKS: Induces T cell anti-tumor responses

AGENTS USED: DPX-E7, an immunotherapy for the treatment of Human Papillomavirus 16-positive (HPV16+) cancers.

DISEASE TARGETED: HPV+ advanced, metastatic, or recurrent head and neck cancer; anal, and cervical HPV+ cancers

WHERE BEING CONDUCTED: Not specified

TRIAL STATUS (as of 2019): Phase 1/2 clinical trial

TRIAL SPONSOR: IMV Inc. and Dana Farber Cancer Center
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ClinicalTrials.gov identifier: NCT03978689

FOCUS OF THE THERAPY: CUE-101 is a novel fusion protein designed to activate and expand a population of tumor specific T cells to eradicate human papilloma virus (HPV)-driven malignancies. HPV causes multiple tumor types including cervical, head and neck squamous cell carcinoma (HNSCC) and anal cancers. Initial testing of CUE-101 will be conducted in HPV16+ HNSCC patients. The primary objectives of the first-in-human trial are to assess the safety and tolerability of CUE-101 in subjects with recurrent/metastatic HNSCC and to determine the maximum tolerated dose or recommended Phase 2 dose based on markers of biological activity. Pharmacokinetics (PK), antitumor immune response, preliminary antitumor activity and the potential for immunogenicity will also be assessed. This will be an open-label multicenter phase I trial conducted in the U.S. involving approximately 50 patients.

HOW IT WORKS: Induces T cell anti-tumor responses

AGENTS USED: CUE-101, an immunotherapy for the treatment of Human Papillomavirus 16-positive (HPV16+) cancers.

DISEASE TARGETED: HPV Positive Oropharyngeal Squamous Cell Carcinoma

WHERE BEING CONDUCTED: Numerous locations across the US

TRIAL STATUS (as of 2020): Phase 1 clinical trial

TRIAL SPONSOR: Cue Biopharma
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ClinicalTrials.gov identifier: NCT02379520

FOCUS OF THE THERAPY: Study evaluating HPV-16/18 E6/E7-Specific T Lymphocytes in patients with Relapsed HPV-Associated Cancers. Tessa’s TT12 is an autologous T cell therapy product composed of HPVSTs that have been trained to target HPV 16/18 antigens and genetically modified with a decoy TGF-β receptor to overcome the immuno-suppressive tumor microenvironment.The safety and optimal dose selection of armored HPVSTs in combination with an anti-PD-1 antibody is currently being evaluated in an ongoing investigator-sponsored Phase 1 trial (NTC02379520) in the United States, in patients with relapsed/resistant HPV-associated cancers.

In collaboration with MSD (tradename of Merck & Co., Inc., Kenilworth, N.J., USA), Tessa will conduct a separate, multi-center Phase 1b/2 trial to evaluate the safety and efficacy of our autologous HPVST therapy in combination with MSD’s anti-programmed death receptor-1 (PD-1) antibody, Pembrolizumab (KEYTRUDA®), following pre-conditioning lymphodepletion chemotherapy, in patients with recurrent/refractory or metastatic HPV 16/18-positive cervical cancer.

HOW IT WORKS: Induces T cell anti-tumor responses.

AGENTS USED: TT12 is an autologous T cell therapy product

DISEASE TARGETED: HPV Positive cancers (all types)

WHERE BEING CONDUCTED: Baylor College of Medicine, Texas
Contact: Carlos Ramos, MD 832-824-4817 caramos@bcm.edu
Contact: Vicky Torrano, RN 832-824-7821 vtorrano@bcm.edu

TRIAL STATUS (as of 2020): Phase 1 clinical trial

TRIAL SPONSOR: Tessa Therapeutics Singapore
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ClinicalTrials.gov identifier: NCT04432597

FOCUS OF THE THERAPY: PRGN-2009 is a first-in-class, off-the-shelf investigational immunotherapy that was developed using the company's UltraVector and AdenoVerse platforms to optimize HPV antigen design. The drug works to stimulate the immune system to recognize and target HPV-positive tumors.

In the Phase I portion of the trial, PRGN-2009 will be administered as a monotherapy to determine the ideal Phase II dose. The Phase II portion of the trial will evaluate the safety of PRGN-2009 as a monotherapy or in combination with an investigational bifunctional fusion protein in patients with newly diagnosed stage II/III HPV16-positive oropharyngeal cancer and in patients with recurrent or metastatic HPV-associated cancers.

HOW IT WORKS: Immunotherapy

AGENTS USED: PRGN-2009

DISEASE TARGETED: HPV Positive cancers

WHERE BEING CONDUCTED: Unknown

TRIAL STATUS (as of 2020): Phase 1 clinical trial to be started

TRIAL SPONSOR: Precigen
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ClinicalTrials.gov identifier: NCT02002182

FOCUS OF THE THERAPY: ADXS 11-001 Vaccination Prior to Robotic Surgery, HPV-Positive Oropharyngeal Cancer

Two vaccinations with ADXS11-001 (ADXS-HPV) will be given at a dose of 1x10^9 cfu intravenously. The drug will be given as a 500ml infusion over 60 minutes.
ADXS11-001 (ADXS-HPV): ADXS11-001 (ADXS-HPV) is a live attenuated Listeria monocytogenes (Lm)-LLO immunotherapy developed for the treatment of HPV-associated dysplasia and malignancy.

HOW IT WORKS: Immunotherapy

AGENTS USED: ADXS11-001

DISEASE TARGETED: HPV Positive cancers. This trial is one of a number of trials being run using this agent against a variety of HPV+ cancers, including cervical and anal cancer.

WHERE BEING CONDUCTED: Houston, TX

TRIAL STATUS (as of 2020): Unclear

TRIAL SPONSOR: Dr. Andrew Sikora, Baylor College of Medicine

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ClinicalTrials.gov identifier: NCT04607850

FOCUS OF THE THERAPY: Prime-boost Vaccine Study in Women With Low-grade Cervical HPV Lesions

A Phase 1b/2, Randomised, Placebo-controlled, Dose-ranging Study to Evaluate Safety, Tolerability and Immunogenicity of a Chimpanzee Adenovirus (ChAdOx1)-Vectored Multigenotype High Risk Human Papillomavirus (hrHPV) Vaccine and Modified Vaccinia Ankara (MVA)-Vectored Multigenotype hrHPV Vaccine in Women With Low-grade HPV-related Cervical Lesions. The study consists of an open label, non-randomised, dose escalation Lead in phase. 9 participants with high-risk HPV, in cohorts of 3 in 3 dose ascending groups, will be vaccinated after SMC safety data reviews. This is followed by a blinded, randomised Main phase with 96 participants with high-risk HPV, in parallel running dose cohorts (three different doses of ChAdOx1-HPV plus two different doses of MVA-HPV versus placebo plus placebo boost). At least 60 of these participants will take part in the immunogenicity sub-study.

HOW IT WORKS: Immunotherapy

AGENTS USED: three different doses of ChAdOx1-HPV plus two different doses of MVA-HPV

DISEASE TARGETED: Women with low grade cervical cancer lesions caused by HPV.

WHERE BEING CONDUCTED: Belgium and the UK

TRIAL STATUS (as of 2020): Not yet recruiting

TRIAL SPONSOR: Vaccitech

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ClinicalTrials.gov identifier: NCT04672980

FOCUS OF THE THERAPY: RTX-321 Monotherapy in Patients With HPV 16+ Tumors

This is a Phase 1, open label, multicenter, multidose, first-in-human (FIH) dose escalation and expansion to determine the safety and tolerability, recommended phase 2 dose and pharmacology, and antitumor activity of RTX-321 in adult patients with persistent, recurrent, or metastatic, unresectable cervical cancer (squamous, adeno, or adenosquamous histology), HNSCC, or squamous cell cancer of the anal canal that is not amenable to curative therapy. Prior to study screening, all patients must be confirmed to be HLA-A*02:01 positive. Documentation of an HPV 16+ tumor is required at prescreening for patients with cervical cancer and HNSCC. RTX-321 is a cellular therapy that expresses 4-1BBL, IL-12, and HPV-16 Antigen with the goal of harnessing the innate and adaptive immune systems for the treatment of cancer. The study will include a monotherapy dose escalation phase followed by an expansion phase.

HOW IT WORKS: Immunotherapy

AGENTS USED: RTX-321 is a cellular therapy that expresses 4-1BBL, IL-12, and HPV-16 Antigen

DISEASE TARGETED: Cervical cancer; anal cancer; head and neck cancer.

WHERE BEING CONDUCTED: Los Angeles, CA and Nashville, TN

TRIAL STATUS (as of 2020): Recruiting

TRIAL SPONSOR: Rubius

A paper describing the pre-clinical biology behind this therapy can be found here.

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ClinicalTrials.gov identifier: NCT04260126

FOCUS OF THE THERAPY: Combination of Pembrolizumab (Keytruda) and PDS0101 in an immunotherapy approach for treating HPV+ head and neck cancers

PDS0101 is a novel T-cell immunotherapy delivered subcutaneously that has been shown to stimulate high levels of HPV16-specific CD8+ and CD4+ T cells within patients by activating multiple immune pathways. These HPV-specific T cells then target tumors such as head and neck, anal and cervical cancers that are caused by HPV infection. The number of HNSCC cases has been increasing steadily over the last 10-15 years and over 90% of HPV-positive head and neck cancers are HPV16 positive. Pembrolizumab has been shown to have efficacy against both HPV-positive and HPV-negative head and neck cancers. However, its effectiveness is more optimal in tumors that are PD-L1 positive and have evidence of immune cells within the tumor. We hypothesize that increasing tumor-targeting HPV-specific T-cells with PDS0101 will be associated with an increased response to pembrolizumab. This study will explore in a preliminary manner whether combination treatment with PDS0101 plus pembrolizumab will improve clinical efficacy over that seen with pembrolizumab alone in the KEYNOTE-048 study.

HOW IT WORKS: Immunotherapy

AGENTS USED: PDS0101 and Pembrolizumab (KEYTRUDA®)

DISEASE TARGETED: First Line Treatment in Subjects With Recurrent and/or Metastatic head and neck cancer and High-Risk HPV16 Infection

WHERE BEING CONDUCTED: Multiple sites in the U.S.

TRIAL STATUS (as of 2021): phase II

TRIAL SPONSOR: PDS Biotechnology Corp.

NOTE: details of this phase II study were shared by the sponsor in May 2024. The results appear to be positive for about 1/3 of the patients in the study (VERSATILE-002), but there a number of caveats. The trial was only open to a select sub-group of patients. This study is likely to lead to a phase III trial with a much larger group of patients. Read this summary for more details.

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ClinicalTrials.gov identifier: NCT04084951

FOCUS OF THE THERAPY: Study of SQZ-PBMC-HPV in Patients With HPV16+ Recurrent, Locally Advanced or Metastatic Solid Tumors

A Phase 1, Multicenter, Open-Label, Dose Escalation and Dose Expansion Study of SQZ-PBMC-HPV as Monotherapy and in Combination With Atezolizumab (Tecentriq) or Other Immune Checkpoint Inhibitors in HLA-A*02+ Patients With HPV16+ Recurrent, Locally Advanced or Metastatic Solid Tumors. This is an antigen presenting cell therapy; therapeutic vaccine consisting of peripheral blood mononuclear cells (PBMCs) manufactured with immunogenic epitopes of HPV16.

HOW IT WORKS: Immunotherapy

AGENTS USED: SQZ-PBMC-HPV and Tecentriq or Keytruda

DISEASE TARGETED: First Line Treatment in Subjects With Recurrent and/or Metastatic head and neck cancer and High-Risk HPV16 Infection

WHERE BEING CONDUCTED: Multiple sites in the U.S.

TRIAL STATUS (as of 2021): phase I

TRIAL SPONSOR: SQZ Biotechnologies

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ClinicalTrials.gov identifier: NCT05783622

FOCUS OF THE THERAPY: This study is a first-in-human (FIH), Phase 1/1b, open-label, multicenter dose escalation and dose expansion study to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary anti-tumor activity of JANX008 in adult subjects with advanced or metastatic carcinoma expressing EGFR.

HOW IT WORKS: Immunotherapy

AGENTS USED: Janux008

DISEASE TARGETED: Non-Small Cell Lung Cancer; Renal Cell Carcinoma; Squamous Cell Carcinoma of the Head and Neck; Colorectal Carcinoma

WHERE BEING CONDUCTED: Multiple sites in the U.S.

TRIAL STATUS (as of 2023): phase I/1b

TRIAL SPONSOR: Janux Therapeutics

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ClinicalTrials.gov identifier: NCT05826275

FOCUS OF THE THERAPY: This is an open-label, non-randomized, Phase I, dose escalation/dose expansion study in cohorts of patients with relapsed, resistant, or metastatic HPV-associated cancers. The Expansion Phase will begin in parallel one dose level lower than the highest dose deemed safe in the Dose Escalation in combination with a PD-1 checkpoint blockade. Official title: A Phase 1 Trial of TGN-S11 in Patients With Human Papillomavirus (HPV)-Associated Relapsed, Resistant or Metastatic Cancer. TGN-S11 is thought to be an inhibitor of the E5 oncogene in HPV

HOW IT WORKS: Immunotherapy

AGENTS USED: Two drugs: TGN-S11 and pembrolizumab

DISEASE TARGETED: HPV+ squamous cell carcinoma (organ not specified)

WHERE BEING CONDUCTED: Multiple sites in the U.S. including California, Texas, and New York

TRIAL STATUS (as of 2023): phase 1

TRIAL SPONSOR: Toragen, Inc.

This new approach is also an immunotherapy, but the targets (i.e. the molecules expressed on the cancer cells that we want the immune system to attack) are personalized for each tumor. Put another way, each cancer vaccine is an individual treatment designed only for that one person. The hope is that by customizing the vaccine it will lead to the most efficacious treatment possible. Various techniques are being used to generate these therapeutic (not preventative) vaccines.

A basic version of this process is shown in the graphic below, illustrating how tumor cells are removed and used to create the vaccine. Neoantigens are novel proteins not normally found in the body, and therefore they make good targets for immunotherapy treatments.

You can read more about this basic concept in this article by Jasreet Hundal and Elaine Mardis Personalized Cancer Vaccines in Clinical Trials, published in The Scientist in July 2019.The article includes a more complete version of the Table below with individual trial listings. Ask your doctor if you are interested in participating in one of these trials.

I just wanted to throw this in to the mix even though this technique is not ready yet for the clinical treatment of HPV+ cancers. In short, a gene therapy approach called CRISPR may someday be useful in treating HPV cancers. CRISPR is a technique that can specifically target HPV within tumor cells. A recent paper showed that CRISPR in a mouse cancer model was effective at eliminating HPV caused tumors. It’s not ready for prime time for this purpose, but the CRISPR technique is just starting to be used for other clinical trials, and is thought to have great potential. I’ll keep an eye on this and update the page should this actually move forward into the clinic. In the meantime, here’s a link to the mouse paper:

Jubair, L et al Systemic Delivery of CRISPR/Cas9 targeting HPV oncogenes is effective at eliminating established tumors. Molecular Therapy (published online Aug. 2019)