Understanding severe HPV-related diseases

* 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.