Human PapillomavirusNCT05026138
Natural History, Epidemiology and Pathogenesis of Severe HPV-Related Diseases (Neptune)
An observational study of Human Papillomavirus, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial summary
Background: Most symptoms of human papillomaviruses (HPV) infection, do not cause serious health problems, but some do. As HPV can cause uncontrolled growth of infected cells, some people can develop benign skin lesions, larger warts, genital lesions, tumors or cysts that do not respond to treatment. Read more about this study
- Who is it for?
- Ages 3 to 100 yearsHealthy volunteers can take part
- Conditions the study is for
- Human Papillomavirus
- How many people
- 850 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Nov 2021to 31 Mar 2047
- Phase
- Observational
- 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 3 to 100 years
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Study population: Participants will have HPV infection with severe, disseminated, recurrent, and treatment-refractory HPV related skin and mucosal disease. Healthy biological relatives, household contacts, and/or sexual partners will also be recruited to serve as controls for research tests.
Who may be able to join
- Aged >=3 years (except for household contacts and sexual partners of participants with HPV-related diseases, who must be aged 18 years and older).
- Able to provide informed consent or, if younger than 18, be accompanied by a parent(s)/legal guardian(s) who is able to provide informed consent.
- Willing to allow genetic testing on their collected biological samples.
- Additional Inclusion Criteria for Participants with HPV-related Diseases
- Has severe, disseminated, recurrent, and treatment-refractory HPV infection, defined as one or more of the following confirmed by medical record review or participant health history:
- In participants without known primary or acquired immunodeficiency:
Show all 20Show fewer
- Multiple skin warts (>=5) recurrent* or refractory to standard-of-care interventions (eg, topical imiquimod, acetylsalicylic acid, cryotherapy, cantharidin, podophyllotoxin, bleomycin, cauterization, cidofovir, fluorouracil).
- Concomitant skin warts (irrespective to recurrence or treatment response) AND any historical or current clinical and/or histologic or cytologic evidence of mucosal HPV-related diseases (oral, nasal, laryngeal, vaginal, anal, penile, or cervical).
- Mucosal condyloma or other HPV-related diseases that are recurrent* or refractory to standard-of-care interventions.
- Historical evidence of mucosal condyloma or any HPV-related diseases occurring irrespective of response to standard-of-care interventions and involving more than one mucosal site.
- In participants with known primary or acquired immunological defect (including idiopathic CD4 lymphopenia, immunosuppressive treatment, or HIV/AIDS):
- Any skin OR mucosal HPV-related diseases
- In any participant:
- Recurrent invasive skin or mucosal HPV-related squamous cell carcinoma (HPV-SCC).
- Historical or current histologic evidence of invasive HPV-SCC of any mucosal site in subjects with family history of HPV-SCC in 1 or more family members.
- The lack of complete response to 2 or more interventions is defined as treatment-refractory disease in the protocol, while the reappearance of a skin or mucosal lesion after complete resolution is defined as recurrence.
- Additional Inclusion Criteria for Controls
- 1. Biological relative, household contact, or sexual partner of the index participant (with HPV-related diseases) who meets one of the following criteria:
- does not have any historical or current clinical and/or histologic or cytologic evidence of skin or mucosal HPV-related diseases, or
- has historical or current clinical and/or histologic or cytologic evidence of skin or mucosal HPV-related diseases but does not meet the criteria to be enrolled in this study as a participant with HPV-related disease.
Who cannot join
- Individuals meeting any of the following criteria will be excluded from study participation:
- Laboratory abnormalities contraindicating research evaluations and procedures in patients without previous history of cytopenias: neutropenia (absolute neutrophil count <500 cells/microL) or thrombocytopenia (platelets <10,000/microL). Medical record review may be used to for determining eligibility if the laboratory tests were collected <= 90 days prior to the screening visit.
- Inability to reliably keep research appointments and/or adhere to research procedures.
- Any condition that, in the opinion of the investigator, contraindicates participation in this study.
- Additional Exclusion Criteria for Controls
- 1. Has HPV-related disease that may indicate enrollment as an affected participant rather than as a healthy biological relative, household contact, or sexual partner.
- Co-enrollment guidelines: Participants may be co-enrolled in other studies; however, study staff should be notified of co-enrollment.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR), 800-411-1222 ext. TTY8664111010, prpl@cc.nih.gov
About this study
Background:
Most symptoms of human papillomaviruses (HPV) infection, do not cause serious health problems, but some do. As HPV can cause uncontrolled growth of infected cells, some people can develop benign skin lesions, larger warts, genital lesions, tumors or cysts that do not respond to treatment. Researchers want to learn why.
Read more
Objective:
To better understand why some people are more likely than others to get sick from HPV infection, and why medicine or surgery is not always effective.
Eligibility:
People aged 3 years and older who have had multiple outbreaks of HPV-related warts and/or lesions that do not respond to treatment. Healthy relatives are also needed.
Design:
Participants will be screened with a medical history, physical exam, and blood tests.
Participants may have study visits as an outpatient or an inpatient (admitted overnight to the NIH hospital) and be followed over several years by our doctors and researchers at the NIH.
Participants may have a cervical and/or anal Pap test. They may give samples of semen, cervicovaginal secretions, urine, saliva, or stool. Small pieces of skin, the inside of the cheek, and/or the gums may be collected with a punch or scrape biopsy to understand how HPV affect the growth of cells.
Mucus and skin may be collected by rubbing the area with a cotton swab. Collection areas may include the inside the mouth, nostrils, skin, genitals, and/or in or around the anus.
Biopsies may be collected. If participants need to have a biopsy as part of medical care, then we may ask if extra samples can be collected for research. Biopsies we may collect are bone marrow, lymph node, genitals, or in or around the anus.
Participants may have leukapheresis. Blood is taken from a needle placed in one arm. A machine separates out the white blood cells. The rest of the blood is returned through a needle in their other arm.
Samples may be used for genetic tests and/or to make special cells called induced pluripotent stem cells.
Participants may have follow-up visits once a year for 10 years.
Benefits:
We are not testing new HPV treatments in this study and you might not benefit from participating. However, we may learn new information about your condition that we will share with you and your doctor. We may make recommendations for your medical care based on current accepted treatment.
What we learn from you and other participants in this study might help other people. We hope we can use this information to develop new treatments and therapies in the future....
Read the detailed description
Study Design: This is a prospective, longitudinal natural history study. Total length of individual participation is 10 years.
Primary Objective: To define the clinical, immunologic, and genetic bases of severe disseminated, recurrent, and treatment-refractory HPV-related skin and mucosal disease.
Secondary Objectives:
- Identify novel genetic defects associated with severe HPV-related diseases.
- Define the natural history of HPV infections on skin and mucosal tissue in immunocompromised hosts.
- Define the epidemiology of skin and mucosal HPV variants in immunocompromised hosts by next-generation sequencing.
- Define the distribution of immune cells in skin and mucosal surfaces of patients with severe HPV-related diseases and immunologic correlates of HPV-disease progression.
Primary Endpoint: Identify novel immunologic and/or genetic determinants of the susceptibility to severe disseminated, recurrent, and
treatment-refractory HPV-related diseases.
Secondary Endpoints: 1. Identify virologic, clinical, and immunologic predictors of progressive HPV-related diseases.
- Define the cellular and functional components involved in control or lack thereof of HPV infection in different cutaneous and mucosal surfaces.
The purpose of this study is to identify clinical and immunologic correlates of increased susceptibility to human papillomavirus (HPV) infections, HPV related dysplasia/cancer, or any other HPV-related clinical manifestations. We will enroll patients with disseminated, multifocal or recurrent HPV-related diseases refractory to standard-of-care medical or surgical interventions. Healthy family members household contacts, and/or sexual partners will also be enrolled as comparators. This protocol will allow long-term follow-up of patients with primary or acquired immunologic abnormalities associated with such increased susceptibility to HPV-related diseases. It will also allow periodic clinical and laboratory evaluation with collection of blood, biological fluids, tissue and mucosal swabs, and tissue biopsies for medically indicated purposes. Additional research studies on these samples will be aimed to identify genetic and immunologic bases of their HPV-related diseases and inform the development of specific and effective treatment interventions.
- Conditions
- Human Papillomavirus
- Keywords
- Mucosal Disease, Immunocompromised, Genetic Defects, Infection, Neoplasia, Natural History
- Medical subject headings
- Infections, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Biological relatives without HPV | Biological relatives, household contacts, and/or sexual partners without current HPV disease serving as controls to be compared with those from affected participants for evaluation of the differences between people with HPV and without. | |
| Participants with HPV | Patients with recurrent HPV related diseases refractory to standard-of-care medical or surgical interventions. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Identify novel immunologic and/or genetic determinants of the susceptibility to severe disseminated, recurrent, and treatment-refractory HPV-related diseases.
To define the clinical, immunologic, and genetic bases of severe disseminated, recurrent, and treatment-refractory HPV-related skin and mucosal disease.
Measured: Throughout the study
Secondary outcomes (2)
Identify virologic, clinical, and immunologic predictors of progressive HPV-related diseases
Identify novel genetic defects associated with severe HPV related diseases.
Measured: Throughout the study
Define the cellular and functional components involved in control or lack thereof of HPV infection in different cutaneous and mucosal surfaces
Define the natural history of HPV infections on skin and mucosal tissue in immunocompromised hosts; Define the epidemiology of skin and mucosal HPV variants in immunocompromised hosts by next-generation sequencing; Define the distribution of immune cells in skin and mucosal surfaces of patients with severe HPV-related diseases and immunologic correlates of HPV-disease progression.
Measured: Throughout the study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Aug 2021
- Study start17 Nov 2021
- Primary completion31 Mar 2047 (estimated)
- Study completion31 Mar 2047 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Human PapillomavirusStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 850 participants (estimated)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Andrea Lisco, M.D., Principal investigator, National Institute of Allergy and Infectious Diseases (NIAID)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05026138
- Sponsor's protocol ID
- 210029
- Other IDs
- 21-I-0029
- Status last verified
- 26 Jun 2026
- First submitted
- 27 Aug 2021
- Last updated
- 6 Jul 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Natural History, Epidemiology and Pathogenesis of Severe HPV-Related Diseases (Neptune)
- ClinicalTrials.gov ID
- NCT05026138
- Acronym / sponsor ID
- 210029
- Conditions
- Human Papillomavirus
- Keywords
- Mucosal Disease, Immunocompromised, Genetic Defects, Infection, Neoplasia, Natural History
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 850 participants (estimated)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 17 Nov 2021 (actual)
- Primary completion
- 31 Mar 2047 (estimated)
- Study completion
- 31 Mar 2047 (estimated)
- First posted
- 30 Aug 2021 (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.
Background:
Most symptoms of human papillomaviruses (HPV) infection, do not cause serious health problems, but some do. As HPV can cause uncontrolled growth of infected cells, some people can develop benign skin lesions, larger warts, genital lesions, tumors or cysts that do not respond to treatment. Researchers want to learn why.
Objective:
To better understand why some people are more likely than others to get sick from HPV infection, and why medicine or surgery is not always effective.
Eligibility:
People aged 3 years and older who have had multiple outbreaks of HPV-related warts and/or lesions that do not respond to treatment. Healthy relatives are also needed.
Design:
Participants will be screened with a medical history, physical exam, and blood tests.
Participants may have study visits as an outpatient or an inpatient (admitted overnight to the NIH hospital) and be followed over several years by our doctors and researchers at the NIH.
Participants may have a cervical and/or anal Pap test. They may give samples of semen, cervicovaginal secretions, urine, saliva, or stool. Small pieces of skin, the inside of the cheek, and/or the gums may be collected with a punch or scrape biopsy to understand how HPV affect the growth of cells.
Mucus and skin may be collected by rubbing the area with a cotton swab. Collection areas may include the inside the mouth, nostrils, skin, genitals, and/or in or around the anus.
Biopsies may be collected. If participants need to have a biopsy as part of medical care, then we may ask if extra samples can be collected for research. Biopsies we may collect are bone marrow, lymph node, genitals, or in or around the anus.
Participants may have leukapheresis. Blood is taken from a needle placed in one arm. A machine separates out the white blood cells. The rest of the blood is returned through a needle in their other arm.
Samples may be used for genetic tests and/or to make special cells called induced pluripotent stem cells.
Participants may have follow-up visits once a year for 10 years.
Benefits:
We are not testing new HPV treatments in this study and you might not benefit from participating. However, we may learn new information about your condition that we will share with you and your doctor. We may make recommendations for your medical care based on current accepted treatment.
What we learn from you and other participants in this study might help other people. We hope we can use this information to develop new treatments and therapies in the future....
Detailed description
Study Design: This is a prospective, longitudinal natural history study. Total length of individual participation is 10 years.
Primary Objective: To define the clinical, immunologic, and genetic bases of severe disseminated, recurrent, and treatment-refractory HPV-related skin and mucosal disease.
Secondary Objectives:
- Identify novel genetic defects associated with severe HPV-related diseases.
- Define the natural history of HPV infections on skin and mucosal tissue in immunocompromised hosts.
- Define the epidemiology of skin and mucosal HPV variants in immunocompromised hosts by next-generation sequencing.
- Define the distribution of immune cells in skin and mucosal surfaces of patients with severe HPV-related diseases and immunologic correlates of HPV-disease progression.
Primary Endpoint: Identify novel immunologic and/or genetic determinants of the susceptibility to severe disseminated, recurrent, and
treatment-refractory HPV-related diseases.
Secondary Endpoints: 1. Identify virologic, clinical, and immunologic predictors of progressive HPV-related diseases.
- Define the cellular and functional components involved in control or lack thereof of HPV infection in different cutaneous and mucosal surfaces.
The purpose of this study is to identify clinical and immunologic correlates of increased susceptibility to human papillomavirus (HPV) infections, HPV related dysplasia/cancer, or any other HPV-related clinical manifestations. We will enroll patients with disseminated, multifocal or recurrent HPV-related diseases refractory to standard-of-care medical or surgical interventions. Healthy family members household contacts, and/or sexual partners will also be enrolled as comparators. This protocol will allow long-term follow-up of patients with primary or acquired immunologic abnormalities associated with such increased susceptibility to HPV-related diseases. It will also allow periodic clinical and laboratory evaluation with collection of blood, biological fluids, tissue and mucosal swabs, and tissue biopsies for medically indicated purposes. Additional research studies on these samples will be aimed to identify genetic and immunologic bases of their HPV-related diseases and inform the development of specific and effective treatment interventions.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Biological relatives without HPV | – | –Biological relatives, household contacts, and/or sexual partners without current HPV disease serving as controls to be compared with those from affected participants for evaluation of the differences between people with HPV and without. |
| Participants with HPV | – | –Patients with recurrent HPV related diseases refractory to standard-of-care medical or surgical interventions. |
Who may qualify
- Ages
- 3 to 100 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Participants will have HPV infection with severe, disseminated, recurrent, and treatment-refractory HPV related skin and mucosal disease. Healthy biological relatives, household contacts, and/or sexual partners will also be recruited to serve as controls for research tests.
Key inclusion criteria (20 listed)
- Aged >=3 years (except for household contacts and sexual partners of participants with HPV-related diseases, who must be aged 18 years and older).
- Able to provide informed consent or, if younger than 18, be accompanied by a parent(s)/legal guardian(s) who is able to provide informed consent.
- Willing to allow genetic testing on their collected biological samples.
- Additional Inclusion Criteria for Participants with HPV-related Diseases
- Has severe, disseminated, recurrent, and treatment-refractory HPV infection, defined as one or more of the following confirmed by medical record review or participant health history:
Key exclusion criteria (7 listed)
- Individuals meeting any of the following criteria will be excluded from study participation:
- Laboratory abnormalities contraindicating research evaluations and procedures in patients without previous history of cytopenias: neutropenia (absolute neutrophil count <500 cells/microL) or thrombocytopenia (platelets <10,000/microL). Medical record review may be used to for determining eligibility if the laboratory tests were collected <= 90 days prior to the screening visit.
- Inability to reliably keep research appointments and/or adhere to research procedures.
- Any condition that, in the opinion of the investigator, contraindicates participation in this study.
- Additional Exclusion Criteria for Controls
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Identify novel immunologic and/or genetic determinants of the susceptibility to severe disseminated, recurrent, and treatment-refractory HPV-related diseases.
Time frame: Throughout the study
To define the clinical, immunologic, and genetic bases of severe disseminated, recurrent, and treatment-refractory HPV-related skin and mucosal disease.
2 secondary outcomes
Identify virologic, clinical, and immunologic predictors of progressive HPV-related diseases
Time frame: Throughout the study
Define the cellular and functional components involved in control or lack thereof of HPV infection in different cutaneous and mucosal surfaces
Time frame: Throughout the study
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 6 Jul 2026.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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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.
Andrea Lisco, M.D. principal investigator
National Institute of Allergy and Infectious Diseases (NIAID)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Human Papillomavirus, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
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 20 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: looking for participants now, as of the sponsor's last update on 6 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
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?
Contact Andrea Lisco, M.D. ((301) 761-7122, andrea.lisco@nih.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Identify novel immunologic and/or genetic determinants of the susceptibility to severe disseminated, recurrent, and treatment-refractory HPV-related diseases. (time frame: Throughout the study). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 6 Jul 2026.