HPV Positive Oropharyngeal Squamous Cell CarcinomaPhase 3NCT04255849
Nine-valent HPV Vaccine to Prevent Persistent Oral HPV Infection in Men Living With HIV
A Phase 3 study testing 9 valent human papillomavirus vaccine (Types 6, 11, 16, 18, 31, 33, 45, 52, 58) in people with HPV Positive Oropharyngeal Squamous Cell Carcinoma and HIV-1-infection, run by Weill Medical College of Cornell University at 3 sites in 3 countries.
Trial summary
This is a randomized, double-blinded, placebo-controlled Phase III interventional trial of the nine-valent HPV vaccine (9vHPV) to prevent persistent oral HPV infection in adult men living with HIV. Read more about this study
- Who is it for?
- Ages 20 to 50 years, men only
- Conditions the study is for
- HPV Positive Oropharyngeal Squamous Cell Carcinoma, HIV-1-infection, HPV Infection
- What is being tested?
- 9 valent human papillomavirus vaccine (Types 6, 11, 16, 18, 31, 33, 45, 52, 58)
- Type of treatment
- Vaccines
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 700 participants
- Where
- 3 sitesin 3 countries
- Study dates
- 23 Feb 2021to 31 Dec 2026
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 50 years
- Men only
- No healthy volunteers
- Adult
Who may be able to join
- HIV-1 infection
- Receipt of antiretroviral therapy for at least 6 months
- Sexually active in the past 6 months; sexual activity is defined as insertive penile-vaginal sex, receptive or insertive penile-anal sex, oral-anal sex, or oral-genital sex Willingness to comply with three-dose vaccine schedule and subsequent six-month visits for up to four years after randomization.
Who cannot join
- Have a history of oropharyngeal cancer (OPC) or other HPV-related cancer or have suspected OPC or other HPV-related cancer;
- Have received any doses of a licensed or experimental HPV vaccine or have participated in an HPV vaccine study,
- Have a history of anaphylaxis to vaccines or are allergic to any vaccine component (e.g.aluminum, yeast, benzonase);
- Have received any blood products within six months of enrollment, or are currently taking immune-suppressants.
- Currently have warts/lesions in the oral cavity.
- Plan to relocate during the study period.
- Have AIDS-defining condition within 6 months prior to study entry.
Trial locations and contacts
3 sites in 3 countries.
3 sites in 3 countries
Mexico1 site
Instituto Nacional de Salud Pública, Mexico
Cuernavaca, Morelos, 62209
Puerto Rico1 site
University of Puerto Rico AIDS Clinical Trials Unit
San Juan, Purto Rico, 00935
About this study
This is a randomized, double-blinded, placebo-controlled Phase III interventional trial of the nine-valent HPV vaccine (9vHPV) to prevent persistent oral HPV infection in adult men living with HIV.
Read the detailed description
Men ages 20-50 years living with HIV will be enrolled at affiliated clinical sites of the University of Puerto Rico, the National Institute of Public Health, Mexico, and University of São Paulo, Brazil. Participants will have a baseline blood draw for serum HPV antibodies and stored plasma, an oral rinse for HPV testing, HPV methylation, and EBV co-infection, stored anal and genital samples for HPV testing, as well as a baseline questionnaire about risk factors for oral HPV infection and oropharyngeal cancer.
Seven hundred participants will be randomized in a 1:1 allocation to receive 9vHPV or placebo at Day 1, Month 2, and Month 6. Randomization will be stratified based on clinical site and age (20-30, 31-40, 41- 50 years). The age range of enrolled participants will be monitored to ensure enrollment of an approximately even distribution of participants across the age range. Enrollment will take place during the first 28 months of this study.
Follow-up testing for oral HPV will be conducted at Months 2, 6, 7, 12 and every 6 months thereafter up to 54 months post-vaccination. The rationale for oral testing at Months 2 and 6 is to identify participants who are oral HPV positive prior to receiving the full 3 doses of vaccine. In addition, an optional collection of anal canal and genital specimens (penile head, shaft, scrotum) will occur at Day 1, Months 7, 12 and every 6 months thereafter up to 54 months post-vaccination in those that specifically provided consent. These specimens will be stored for future medical research and will not be analyzed as part of this study. Serum will be stored for HPV antibody testing at month 7, 12 and every 12 months thereafter. Additionally, 20ml of whole blood will be collected beginning at Month 12 and every 12 months thereafter for DNA methylation of biological aging and circulating tumor HPV DNA (ctHPVDNA) analysis. Participants will undergo a follow-up questionnaire on risk factors for oral HPV and oropharyngeal cancer. Participants will be assessed for adverse events at each follow-up visit. This is a 5-year study. Participants who received placebo will be offered 9vHPV vaccine when the study is unblinded.
The trial analyses will be case driven with case counting commencing at Month 7, one month post-dose 3. The primary analysis will take place when at least 14 cases of the primary endpoint (incident persistent oral HPV infection with HPV types 6, 11, 16, 18, 31, 33, 45, 52, or 58) have been observed.
Early data on the baseline oral HPV prevalence among ULACNet-201 participants suggests an approximately 50% lower prevalence of oral HPV than anticipated. This suggests that oral HPV incidence will likely be significantly lower than anticipated. The reasons for this are not yet clear. To help speed the time until the required number of primary endpoint events is accrued, the number of events needed for the primary endpoint have been changed from 31 to 14. The sample size will also be increased by 40% (from 500 to 700 participants), of which a majority will be enrolled from sites in Mexico. Adding 200 participants will increase the number of follow-up visits where additional eligible primary endpoint events can occur. This allows for additional sample size should loss to follow-up increase. In addition, follow-up time will be extended from 42 months post-vaccination to 54 months post-vaccination to allow for accrual of at least 14 events.
- Being tested
- 9 valent human papillomavirus vaccine (Types 6, 11, 16, 18, 31, 33, 45, 52, 58), Saline Placebo
- Medical subject headings
- Papillomavirus Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
9 valent human papillomavirus vaccine (Types 6, 11, 16, 18, 31, 33, 45, 52, 58)Biological
Gardasil-9 HPV vaccine
Saline PlaceboOther
Saline Placebo
| Study group | Role | What they receive |
|---|---|---|
| 9-valent HPV vaccine | Experimental | Participants receive 9-valent HPV vaccine 0.5mL at entry, Month 2 and Month 6 Receives: Biological: 9 valent human papillomavirus vaccine (Types 6, 11, 16, 18, 31, 33, 45, 52, 58) |
| Saline Placebo | Placebo comparator | Participants receive 0.9% NaCl 0.5 mL at entry, Month 2 and Month 6 Receives: Other: Saline Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with new persistent oral HPV infections with one or more of the following types: 6, 11, 16, 18, 31, 33, 45, 52, or 58
The primary endpoint is incident persistent oral HPV infection with HPV types 6, 11, 16, 18, 31, 33, 45, 52, or 58 occurring among participants who remain oral HPV negative to the relevant HPV type through the vaccination period (Day 1-Month 6). Newly acquired oral HPV infections that persist for two or more consecutive oral HPV assessments at least 16 weeks apart with the same 9vHPV detected are defined as "persistent". Case counting will commence with the Month 7 clinical visit and may occur at any timepoint through the final visit.
Measured: From Month 7 up to Month 60
Secondary outcomes (2)
Immunogenicity of 9-valent HPV vaccine as measured by proportion of participants experiencing seroconversion for vaccine type.
To evaluate our secondary immunogenicity endpoint, we will assess the proportion of men who seroconvert to the HPV vaccine types 6, 11, 16, 18, 31, 33, 45, 52, or 58 (both in grouped and type-specific analyses) in serum one month post-dose three (Month 7) using the Wilson's method. Men who enter the study seronegative for a particular HPV vaccine type will be monitored for seroconversion following three doses of 9vHPV.
Measured: Month 7
Safety and tolerability of 9-valent HPV vaccine as measured by proportion of participants with >= grade 3 adverse events related to study vaccination or Grade 1 or 2 events leading to premature discontinuation of vaccination, or serious adverse events.
To evaluate the secondary safety and tolerability endpoint, we will report the proportion of participants experiencing a grade 3 or 4 adverse event at least possibly related to study vaccine, grade 1 or 2 adverse events leading to premature discontinuation of vaccine or placebo, and serious adverse events.
Measured: Baseline through Month 7
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Feb 2020
- Study start23 Feb 2021
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HPV Positive Oropharyngeal Squamous Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by Weill Medical College of Cornell UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 700 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Weill Medical College of Cornell University
- Sponsor type
- University, hospital or other
- Collaborators
- H. Lee Moffitt Cancer Center and Research Institute, University of Sao Paulo, University of Puerto Rico, National Cancer Institute (NCI), Merck Sharp & Dohme LLC, University of California, San Diego, Instituto Nacional de Salud Publica, Mexico
- Responsible party
- Sponsor
- Investigators
- Grant Ellsworth, MD, MS, Principal investigator, Weill Medical College of Cornell University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04255849
- Sponsor's protocol ID
- 19-11021038
- Other IDs
- U54CA242639
- Status last verified
- Sep 2026
- First submitted
- 31 Jan 2020
- Last updated
- 14 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data that underlie results in the publication, after deidentification
Publications
Giuliano AR, Beltrame A, Villa LL, Lazcano-Ponce E, Santana-Bagur J, Allen-Leigh B, Portillo-Romero AJ, Sahasrabuddhe VV, House MG, Brofsky E, Galan de Paula L, Carvalho da Silva R, Schell MJ, Rathwell J, Isaacs-Soriano K, Fan W, Mello C, Ellsworth GB, Wilkin T. Design of a multicenter, randomized, double-blinded, placebo-controlled phase III trial evaluating the 9-valent human papillomavirus (HPV) vaccine to prevent persistent oral HPV infection in men living with human immunodeficiency virus: ULACNet trial 201. Vaccine. 2025 Aug 13;61:127447. doi: 10.1016/j.vaccine.2025.127447. Epub 2025 Jul 2.
PubMed 40609265
Study at a glance
From the registry record, last updated by the sponsor on 14 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Nine-valent HPV Vaccine to Prevent Persistent Oral HPV Infection in Men Living With HIV
- ClinicalTrials.gov ID
- NCT04255849
- Acronym / sponsor ID
- 19-11021038
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 700 participants (estimated)
- Lead sponsor
- Weill Medical College of Cornell UniversityUniversity, hospital or other
- Collaborators
- H. Lee Moffitt Cancer Center and Research Institute, University of Sao Paulo, University of Puerto Rico, National Cancer Institute (NCI), Merck Sharp & Dohme LLC, University of California, San Diego, Instituto Nacional de Salud Publica, Mexico
- Study start
- 23 Feb 2021 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 5 Feb 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a randomized, double-blinded, placebo-controlled Phase III interventional trial of the nine-valent HPV vaccine (9vHPV) to prevent persistent oral HPV infection in adult men living with HIV.
Detailed description
Men ages 20-50 years living with HIV will be enrolled at affiliated clinical sites of the University of Puerto Rico, the National Institute of Public Health, Mexico, and University of São Paulo, Brazil. Participants will have a baseline blood draw for serum HPV antibodies and stored plasma, an oral rinse for HPV testing, HPV methylation, and EBV co-infection, stored anal and genital samples for HPV testing, as well as a baseline questionnaire about risk factors for oral HPV infection and oropharyngeal cancer.
Seven hundred participants will be randomized in a 1:1 allocation to receive 9vHPV or placebo at Day 1, Month 2, and Month 6. Randomization will be stratified based on clinical site and age (20-30, 31-40, 41- 50 years). The age range of enrolled participants will be monitored to ensure enrollment of an approximately even distribution of participants across the age range. Enrollment will take place during the first 28 months of this study.
Follow-up testing for oral HPV will be conducted at Months 2, 6, 7, 12 and every 6 months thereafter up to 54 months post-vaccination. The rationale for oral testing at Months 2 and 6 is to identify participants who are oral HPV positive prior to receiving the full 3 doses of vaccine. In addition, an optional collection of anal canal and genital specimens (penile head, shaft, scrotum) will occur at Day 1, Months 7, 12 and every 6 months thereafter up to 54 months post-vaccination in those that specifically provided consent. These specimens will be stored for future medical research and will not be analyzed as part of this study. Serum will be stored for HPV antibody testing at month 7, 12 and every 12 months thereafter. Additionally, 20ml of whole blood will be collected beginning at Month 12 and every 12 months thereafter for DNA methylation of biological aging and circulating tumor HPV DNA (ctHPVDNA) analysis. Participants will undergo a follow-up questionnaire on risk factors for oral HPV and oropharyngeal cancer. Participants will be assessed for adverse events at each follow-up visit. This is a 5-year study. Participants who received placebo will be offered 9vHPV vaccine when the study is unblinded.
The trial analyses will be case driven with case counting commencing at Month 7, one month post-dose 3. The primary analysis will take place when at least 14 cases of the primary endpoint (incident persistent oral HPV infection with HPV types 6, 11, 16, 18, 31, 33, 45, 52, or 58) have been observed.
Early data on the baseline oral HPV prevalence among ULACNet-201 participants suggests an approximately 50% lower prevalence of oral HPV than anticipated. This suggests that oral HPV incidence will likely be significantly lower than anticipated. The reasons for this are not yet clear. To help speed the time until the required number of primary endpoint events is accrued, the number of events needed for the primary endpoint have been changed from 31 to 14. The sample size will also be increased by 40% (from 500 to 700 participants), of which a majority will be enrolled from sites in Mexico. Adding 200 participants will increase the number of follow-up visits where additional eligible primary endpoint events can occur. This allows for additional sample size should loss to follow-up increase. In addition, follow-up time will be extended from 42 months post-vaccination to 54 months post-vaccination to allow for accrual of at least 14 events.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 9-valent HPV vaccine | Experimental | Biological: 9 valent human papillomavirus vaccine (Types 6, 11, 16, 18, 31, 33, 45, 52, 58)Participants receive 9-valent HPV vaccine 0.5mL at entry, Month 2 and Month 6 |
| Saline Placebo | Placebo comparator | Other: Saline PlaceboParticipants receive 0.9% NaCl 0.5 mL at entry, Month 2 and Month 6 |
Who may qualify
- Ages
- 20 to 50 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- HIV-1 infection
- Receipt of antiretroviral therapy for at least 6 months
- Sexually active in the past 6 months; sexual activity is defined as insertive penile-vaginal sex, receptive or insertive penile-anal sex, oral-anal sex, or oral-genital sex Willingness to comply with three-dose vaccine schedule and subsequent six-month visits for up to four years after randomization.
Key exclusion criteria (7 listed)
- Have a history of oropharyngeal cancer (OPC) or other HPV-related cancer or have suspected OPC or other HPV-related cancer;
- Have received any doses of a licensed or experimental HPV vaccine or have participated in an HPV vaccine study,
- Have a history of anaphylaxis to vaccines or are allergic to any vaccine component (e.g.aluminum, yeast, benzonase);
- Have received any blood products within six months of enrollment, or are currently taking immune-suppressants.
- Currently have warts/lesions in the oral cavity.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 9 valent human papillomavirus vaccine (Types 6, 11, 16, 18, 31, 33, 45, 52, 58)Gardasil-9 HPV vaccine | Biological | 9-valent HPV vaccine |
| Saline PlaceboSaline Placebo | Other | Saline Placebo |
Primary outcome
Number of participants with new persistent oral HPV infections with one or more of the following types: 6, 11, 16, 18, 31, 33, 45, 52, or 58
Time frame: From Month 7 up to Month 60
The primary endpoint is incident persistent oral HPV infection with HPV types 6, 11, 16, 18, 31, 33, 45, 52, or 58 occurring among participants who remain oral HPV negative to the relevant HPV type through the vaccination period (Day 1-Month 6). Newly acquired oral HPV infections that persist for two or more consecutive oral HPV assessments at least 16 weeks apart with the same 9vHPV detected are defined as "persistent". Case counting will commence with the Month 7 clinical visit and may occur at any timepoint through the final visit.
2 secondary outcomes
Immunogenicity of 9-valent HPV vaccine as measured by proportion of participants experiencing seroconversion for vaccine type.
Time frame: Month 7
Safety and tolerability of 9-valent HPV vaccine as measured by proportion of participants with >= grade 3 adverse events related to study vaccination or Grade 1 or 2 events leading to premature discontinuation of vaccination, or serious adverse events.
Time frame: Baseline through Month 7
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Sep 2026.
- Derived from this study: PubMed 40609265Giuliano AR, Beltrame A, Villa LL, Lazcano-Ponce E, Santana-Bagur J, Allen-Leigh B, Portillo-Romero AJ, Sahasrabuddhe VV, House MG, Brofsky E, Galan de Paula L, Carvalho da Silva R, Schell MJ, Rathwell J, Isaacs-Soriano K, Fan W, Mello C, Ellsworth GB, Wilkin T. Design of a multicenter, randomized, double-blinded, placebo-controlled phase III trial evaluating the 9-valent human papillomavirus (HPV) vaccine to prevent persistent oral HPV infection in men living with human immunodeficiency virus: ULACNet trial 201. Vaccine. 2025 Aug 13;61:127447. doi: 10.1016/j.vaccine.2025.127447. Epub 2025 Jul 2.
- Individual participant dataSharing planned: Yes. Individual participant data that underlie results in the publication, after deidentification
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Grant Ellsworth, MD, MS principal investigator
Weill Medical College of Cornell University
3 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing 9 valent human papillomavirus vaccine (Types 6, 11, 16, 18, 31, 33, 45, 52, 58) in people with HPV Positive Oropharyngeal Squamous Cell Carcinoma and HIV-1-infection, run by Weill Medical College of Cornell University at 3 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 14 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Brazil, Mexico, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with new persistent oral HPV infections with one or more of the following types: 6, 11, 16, 18, 31, 33, 45, 52, or 58 (time frame: From Month 7 up to Month 60). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04255849, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Sep 2026.