Understanding severe HPV-related diseases

Natural History, Epidemiology and Pathogenesis of Severe HPV-Related Diseases (Neptune)

Observational National Institutes of Health Clinical Center (CC) · NCT05026138

This study is looking to understand why some people get severe HPV-related diseases by following those with tough cases and their healthy family members for up to 10 years.

Quick facts

Study typeObservational
Enrollment850 (estimated)
Ages3 Years to 100 Years
SexAll
SponsorNational Institutes of Health Clinical Center (CC) NIH
Locations1 site (Bethesda, Maryland)
Trial IDNCT05026138 on ClinicalTrials.gov

What this trial studies

This observational study aims to investigate the natural history, epidemiology, and pathogenesis of severe diseases caused by human papillomavirus (HPV). It will enroll participants aged 3 years and older who have experienced multiple outbreaks of HPV-related warts or lesions that do not respond to treatment, as well as healthy relatives. The study will involve medical history assessments, physical exams, and blood tests, with participants being followed for up to 10 years to identify genetic and immunologic factors associated with severe HPV infections.

Who should consider this trial

Good fit: Ideal candidates include individuals aged 3 years and older with severe, recurrent, and treatment-refractory HPV infections.

Not a fit: Patients with mild HPV infections that respond well to standard treatments may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to better understanding and management of severe HPV-related diseases, improving treatment outcomes for affected patients.

How similar studies have performed: While there have been studies on HPV, this specific approach focusing on severe, treatment-refractory cases is relatively novel.

Eligibility criteria

Show full inclusion / exclusion criteria
* INCLUSION CRITERIA:

Inclusion Criteria for All Participants

1. Aged \>=3 years (except for household contacts and sexual partners of participants with HPV-related diseases, who must be aged 18 years and older).
2. 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.
3. 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:

1. In participants without known primary or acquired immunodeficiency:

   1. Multiple skin warts (\>=5) recurrent\* or refractory to standard-of-care interventions (eg, topical imiquimod, acetylsalicylic acid, cryotherapy, cantharidin, podophyllotoxin, bleomycin, cauterization, cidofovir, fluorouracil).
   2. 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).
   3. Mucosal condyloma or other HPV-related diseases that are recurrent\* or refractory to standard-of-care interventions.
   4. 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.
2. In participants with known primary or acquired immunological defect (including idiopathic CD4 lymphopenia, immunosuppressive treatment, or HIV/AIDS):

   a. Any skin OR mucosal HPV-related diseases
3. In any participant:

   1. Recurrent invasive skin or mucosal HPV-related squamous cell carcinoma (HPV-SCC).
   2. 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:

1. does not have any historical or current clinical and/or histologic or cytologic evidence of skin or mucosal HPV-related diseases, or
2. 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.

EXCLUSION CRITERIA:

Individuals meeting any of the following criteria will be excluded from study participation:

1. 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.
2. Inability to reliably keep research appointments and/or adhere to research procedures.
3. 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.

Where this trial is running

Bethesda, Maryland

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions Human PapillomavirusMucosal DiseaseImmunocompromisedGenetic DefectsInfectionNeoplasiaNatural History
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.