Neoplasms

All Conditions

Carcinoma

Pharmaceutical Solutions

All Drugs and Chemicals

Vaccines

Immunologic Factors

Patients receive RG1-VLP IM for 3 doses at months 0, 2, and 6 in the absence of disease progression or unacceptable toxicity. Patients may also receive Gardasil-9 via injection for 3 doses at 6 months after the 3rd study vaccination (month 12), then at months 14 and 18 in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection on study and may undergo vaginal swab collection on study.

Patients receive saline placebo IM for 3 doses at months 0, 2, and 6 in the absence of disease progression or unacceptable toxicity. Patients may also receive Gardasil-9 via injection for 3 doses at 6 months after the 3rd saline injection (month 12), then at months 14 and 18 in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection on study and may undergo vaginal swab collection on study.

Undergo blood sample and vaginal swab collection

Biospecimen Collection

HPV16 RG1 VLP Vaccine

Questionnaire Administration

Recombinant Human Papillomavirus Nonavalent Vaccine

Saline

Warner K. Huh

Richard B. Roden

Mario R. Castellanos

Lisa M. Barroilhet

Reinhard Kirnbauer

This phase I trial tests the safety, side effects, and best dose of RG1-virus-like particle (VLP) in preventing human papillomavirus (HPV)-related cancers in women. RG1-VLP is a vaccine that aims to protect against rare HPV types not targeted by currently approved HPV vaccines. HPV is a common sexually-transmitted infection that can cause certain genital and oral cancers. RG1-VLP contains a protein of HPV type 16 (HPV16) with a slightly different structure than the licensed Gardasil-9 vaccine. Gardasil-9 is approved by the Federal Drug Administration to help protect against diseases caused by some types of HPV. Gardasil-9 also contains 9 different HPV proteins. Both vaccines contain alum to stimulate the immune system. The usual approach for the prevention of HPV-related cancers for patients who are at increased risk is to consider the currently approved HPV vaccine like Gardasil-9, as well as to be followed closely by their doctor to watch for the development of cancer via routine pap smears. This trial may allow researchers to find out whether the RG1-VLP vaccine can safely trigger an immune response against HPV in healthy women and if it is better or worse than the usual approach for the prevention of HPV-related cancers.

PRIMARY OBJECTIVE:

I. Assess the safety of RG1-virus-like particles (VLP) in healthy 18-45 years old women at 3 escalating doses.

SECONDARY OBJECTIVES:

I. Determine the immunogenicity of RG1-VLP in healthy 18-45 year old women at 3 escalating doses via the following assays:

Ia. Determine serum antibody responses induced by RG1-VLP vaccination by both human papillomavirus (HPV) 16 L1 VLP and HPV16 L2 RG1-peptide enzyme-linked immunosorbent assay (ELISA); Ib. Determine whether vaccination-induced serum antibody response neutralizes HPV16.

EXPLORATORY OBJECTIVES:

I. Determine whether vaccination-induced serum antibody response broadly neutralizes high risk (hr) HPV other than HPV16.

II. Determine whether vaccination induces a cell-mediated immune (CMI) response.

III. Determine whether vaccination-induced serum antibody response upon passive transfer to naive animals, protects mice against hrHPV pseudovirion (PsV) challenge.

IV. Determine whether vaccination results in changes in local antibody titers in vaginal and oral secretions (via oral rinse) and the effects of vaccination on HPV types in optionally-collected vaginal and oral secretions and eyebrow hair samples between months 0, 7 and 12.

V. Assess the safety of recombinant human papillomavirus nonavalent vaccine (Gardasil-9) in healthy women post-administration of RG1-VLP.

OUTLINE: This is a dose-escalation study of RG1-VLP. Patients are randomized to 1 of 2 arms.

ARM I: Patients receive RG1-VLP intramuscularly (IM) for 3 doses at months 0, 2, and 6 in the absence of disease progression or unacceptable toxicity. Patients may also receive Gardasil-9 via injection for 3 doses at 6 months after the 3rd study vaccination (month 12), then at months 14 and 18 in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection on study and may undergo vaginal swab collection on study.

ARM II: Patients receive saline placebo IM for 3 doses at months 0, 2, and 6 in the absence of disease progression or unacceptable toxicity. Patients may also receive Gardasil-9 via injection for 3 doses at 6 months after the 3rd saline injection (month 12), then at months 14 and 18 in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection on study and may undergo vaginal swab collection on study.

Upon completion of study treatment, patients are followed up to 6 months post-3rd RG1-VLP vaccination/saline injection or up to 14 days post-3rd Gardasil-9 vaccination.

The study staff (excluding the pharmacist) and participants will be blinded to the vaccination arm.

Testing RG1-VLP Vaccine to Prevent HPV-related Cancers

A Dose Escalation Phase I Trial of the Safety and Immunogenicity of RG1-VLP, a Candidate Broadly Protective Vaccine for the Prevention of HPV-Associated Cancer

NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

A dose response relationship with serum neutralizing antibody titer will be tested with linear mixed models or Jonckheere-Terpstra tests as appropriate.

Peripheral blood mononuclear cells will be isolated. There will be five mice for each human subject. The presence or absence of a vaccination serum antibody response will be recorded for each mouse. A dose-response relationship for serum antibody response will be tested with a repeated measures logistic regression analysis, accounting for the repetition of mice per subject.

There will be five mice for each human subject. The presence or absence of a vaccination serum antibody response will be recorded for each mouse. A dose-response relationship for serum antibody response will be tested with a repeated measures logistic regression analysis, accounting for the repetition of mice per subject.

These samples will be submitted for future research related to investigating local antibody responses and HPV deoxyribonucleic acid detection.

Safety of the three escalating doses of RG1-VLP will be assessed by adverse events in terms of severity grade and attribution to vaccination as ordinal outcomes. All toxicities will be tabulated and frequencies and percentages of events will be presented for each vaccine dose cohort. The severity of the adverse events will be assessed using the Common Terminology Criteria for Adverse Events 5.0 and supplemented by Food and Drug Administration "Guidance for Industry: Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventative Vaccine Clinical Trials."

Will be tested for IgG against HPV16 L1 using a VLP-based enzyme-linked immunosorbent assay (ELISA). The HPV16 L2 17-36 peptide will be synthesized and used for an L2 ELISA. A dose response relationship for log antibody response will be tested with a linear mixed model. Will be summarized with frequency and relative frequencies along with 95% confidence intervals by time, vaccine dose group, and visit. As appropriate, Jonckheere-Terpstra or Cochran-Armitage tests will be used to test for dose-response relationships.

In vitro HPV pseudovirion (PsV) neutralization assays will be performed for HPV16 and HPV18 and additional PsV types requested by the National Cancer Institute, using an assay specifically developed for sensitivity to L2-specific as well as L1-specific neutralizing antibodies. A dose response relationship with serum neutralizing antibody titer will be tested with linear mixed models or Jonckheere-Terpstra tests as appropriate. Will be summarized with frequency and relative frequencies along with 95% confidence intervals by time, vaccine dose group, and visit. As appropriate, Cochran-Armitage tests will be used to test for dose-response relationships.

National Cancer Institute (NCI)

Infections

Blood and Lymph Conditions

Symptoms and General Pathology

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Hematologic Neoplasms

Communicable Diseases

Papillomavirus Infections

Hematologic Diseases

Antibodies

Immunoglobulins

Patients undergo standard of care allogeneic stem cell transplant. 6-12 months following transplant, patients receive recombinant human papillomavirus nonavalent vaccine IM on day 0 and at 2 and 6 months in the absence of disease progression or unacceptable toxicity.

Jessica P Hwang

This phase IV trial studies how well Gardasil 9 vaccine works in preventing human papillomavirus (HPV) infection in patients with hematologic malignancies who are undergoing donor stem cell transplant. Vaccines, such as Gardasil 9, may help the body build an effective immune response to kill cancer cells.

PRIMARY OBJECTIVES:

I. To determine the immunogenicity of recombinant human papillomavirus nonavalent vaccine (GARDASIL 9) administered after allogeneic stem cell transplant (SCT) in patients with hematologic malignancy by comparing HPV 9-plex competitive Luminex immunoassay (9-plex cLIA) titers before and after GARDASIL 9 administration.

II. To evaluate the safety and tolerability of GARDASIL 9 administered after allogeneic SCT in patients with hematologic malignancy.

OUTLINE:

Patients undergo standard of care allogeneic stem cell transplant. 6-12 months following transplant, patients receive recombinant human papillomavirus nonavalent vaccine intramuscularly (IM) on day 0 and at 2 and 6 months in the absence of disease progression or unacceptable toxicity.

After completion of study intervention, patients are followed up within 3 days.

Gardasil 9 Vaccine in Preventing HPV Infection in Patients With Hematologic Malignancies Undergoing Donor Stem Cell Transplant

Human Papillomavirus Antibody Response After GARDASIL 9 Vaccination in Patients After Allogeneic Stem Cell Transplantation

Antibody response at 1 month post-dose 3 (month 7) will be compared with baseline antibody level. The study will use results from the 9-plex competitive Luminex immunoassay (9-plex cLIA) test to estimate the antibody response rate at dose 3 with 95% confidence interval (CI). Will apply Student t-test/Wilcoxon test to compare continuous variables between patients who obtained antibody response as defined in the primary endpoint (responders) and those who did not respond (non-responders), and the chi-square test or the Fisher's exact test to assess the association between response status and patients' demographic and clinical characteristics. Logistic regression analysis will be used to assess the multivariate relationship between patient demographic and clinical characteristics on the probability of antibody response.

Safety and tolerability of recombinant human papillomavirus nonavalent vaccine measured by occurrence of grade \>= 3 adverse events (AEs) that are possibly, probably, or definitely related to recombinant human papillomavirus nonavalent vaccine for all 3 vaccine administrations. The study will report the AE rate with a corresponding upper bound of a 1-sided 95% CI.

Antibody persistence at 6 months post-dose 3 will be compared with 1 month post-dose 3. The study will apply a paired t-test with noninferiority hypotheses.

The study will calculate the proportion of patients who are able to complete the 3 shot series of HPV vaccination. Will describe them in terms of demographics, and clinical characteristics.

Antibody titer will be measured repeatedly by the 9-plex cLIA test. Appropriate transformation (e.g. log transformation) of antibody titer will be used in the analyses to satisfy the normality assumption of linear or linear mixed effect model. Geometric mean titers will be used to summarize antibody titer at each time point. Linear mixed effect models for repeated measures analysis will be employed to assess change in antibody titer over time and to compare antibody titer change over time between different patient groups adjusting for other important covariates including disease characteristics (tumor stage, site, pathology), and other patient prognostic factors. Interaction between time and patients' characteristics on the change of antibody titer will be also investigated.

M.D. Anderson Cancer Center

Sexually Transmitted Diseases

Sexually Transmitted Diseases, Viral

Virus Diseases

DNA Virus Infections

Tumor Virus Infections

Genital Diseases

Urogenital Diseases

Disease Attributes

Participants receive the first dose of the recombinant human papillomavirus nonavalent vaccine IM at baseline, at least 30 days prior to the kidney transplant surgery. The second dose is given at least one month after the first dose. The third dose is given at least five months after the first dose and at least three months after the second dose. The timing of the second and third doses is dependent on the scheduling of the kidney transplant surgery. Patients are followed up at 6- and 12-months after the kidney transplant surgery to measure vaccine-induced immune responses. Patients may receive either one, two, or all three vaccine doses prior to the kidney transplant surgery, and are offered additional visits at least one year after the surgery to complete any remaining doses of the three-dose vaccine series. Patients also undergo collection of blood samples and self-collection of cervical/vaginal samples (female participants only) on study.

Undergo self-collection of vaginal/cervical samples

HPV Self-Collection

Marc T Goodman

This phase II trial studies whether the nonavalent human papillomavirus vaccine given to adults prior to kidney transplantation can help the body build and maintain an effective immune response during the post-transplant period when they receive immunosuppressive drugs to prevent transplant rejection. This study will help inform our scientific understanding about vaccine-induced immune responses among immunosuppressed individuals.

PRIMARY OBJECTIVE:

I. To assess human papillomavirus (HPV) vaccine-type-specific seroconversion rates at 12-months post-transplantation among kidney transplant recipients who receive \>= 1 doses of the recombinant human papillomavirus nonavalent vaccine (Gardasil \[registered trademark\] 9 HPV vaccine) \>= 30 days prior to transplantation.

SECONDARY OBJECTIVE:

I. To assess HPV vaccine-type-specific seroconversion rates at 6- and 12-months post-transplantation stratified by number of doses (1, 2, or 3) of the vaccine given pre-transplant among kidney transplant recipients who receive \>= 1 doses of the Gardasil 9 HPV vaccine prior to transplantation.

EXPLORATORY OBJECTIVES:

I. To assess the following among kidney transplant recipients who receive \>= 1 doses of the Gardasil 9 HPV vaccine \>= 30 days prior to transplantation:

Ia. HPV vaccine-type-specific seroconversion rates at 12-months post-transplantation stratified by:

Ii. Time elapsed between last vaccine dose and the transplant procedure; Iii. Variations in dosing and types of post-transplant immunosuppressant medications; and interactions with type of transplant surgery (living donor/deceased donor); Iiii. Differences in human leukocyte antigen (HLA) histocompatibility between donor and recipient; Iiv. Differences in biological sex (i.e. male versus \[vs.\] female) of the transplant recipient; Ib. Stability of HPV vaccine-type-specific geometric mean titers (GMT) at 6 and 12-months post-transplantation and rise in HPV vaccine-type-specific GMT at the 13-month post-transplant visit; Ic. Vaccine safety profile and allograft rejection/opportunistic infections stratified by number of vaccine doses and time between the last vaccine dose and the transplant procedure; Id. HPV detection in samples from the cervix/vagina and oral cavity at baseline (pre-vaccination) and at 6- and 12-months post-vaccination, overall and by number of vaccine doses (1, 2, or 3), sexual behavior, type-specific seroconversion rates, and time elapsed between the last vaccine dose and the transplant procedure.

OUTLINE:

Participants receive the first dose of the recombinant human papillomavirus nonavalent vaccine intramuscularly (IM) at baseline, at least 30 days prior to the kidney transplant surgery. The second dose is given at least one month after the first dose. The third dose is given at least five months after the first dose and at least three months after the second dose. The timing of the second and third doses is dependent on the scheduling of the kidney transplant surgery. Patients are followed up at 6- and 12-months after the kidney transplant surgery to measure vaccine-induced immune responses. Patients may receive either one, two, or all three vaccine doses prior to the kidney transplant surgery, and are offered additional visits at least one year after the surgery to complete any remaining doses of the three-dose vaccine series. Patients also undergo collection of blood samples and self-collection of cervical/vaginal samples (female participants only) on study.

Preventive Human Papillomavirus (HPV) Vaccine Trial in Kidney Transplant Recipients

Immunogenicity of Nonavalent HPV Vaccine Administered Prior to Renal Transplantation in Adults: A Prospective, Single-Arm, Multi-Center Clinical Trial

Descriptive statistics, such as probabilities and exact 95% CIs, will be used to summarize probability of seroconversion at 12 months post-transplant for the following groups: a) time elapsed between last vaccine dose and the transplant procedure, e.g. \< 3 months versus (vs.) \> 3 months. Different groupings will be considered based on observed (e.g. median) and clinical considerations. Time will be summarized using descriptive statistics, e.g. median, interquartile range, or range; groups defined by dosing and types of post-transplant immunosuppressant medications, as well as; b) type of transplant surgery (living donor/deceased donor); c) differences in human leukocyte antigen histocompatibility between donor and recipient; d) differences by biological sex (i.e., male vs. female) of the transplant recipient.

Stability will be evaluated in relation to changes in the type-specific GMTs between the two post-transplant time points (6- and 12-months post-transplant) and reported as follows: (i) decrease: more than 2-fold decrease, (ii) stable: within 2-fold change, and (iii) increase: greater than 2-fold increase. Stability will also be described in relation to the number of vaccine doses (1, 2 or 3) received in the pre-transplant period.

The magnitude of increase in type-specific GMTs at the 13-month post-transplant visit (i.e., 1 month after the booster dose) will be described in relation to the type-specific GMTs at the other post-transplant visits (6 and 12-months post -transplant). Patterns over time will also be explored using graphical techniques. Post-booster dose increase in type-specific GMTs will also be described in relation to the number of vaccine doses (1, 2 or 3) received in the pre-transplant period.

Will be summarized using descriptive statistics, stratified by number of vaccine doses and time between the last vaccine dose and the transplant procedure.

HPV detection in samples from the cervix/vagina, and oral cavity at baseline (pre-vaccination) and at 6- and 12-months post-vaccination, overall and by number of vaccine doses (1, 2, or 3), sexual behavior, type-specific seroconversion rates, and time elapsed between the last vaccine dose and the transplant procedure will be evaluated. All rates of HPV detection will be specified, overall and stratified by number of doses (1, 2, or 3) and time to transplant.

An estimate of the seroconversion rate will be provided along with exact Clopper-Pearson 95% confidence intervals (CIs).

Descriptive statistics, such as probabilities and exact 95% CIs, will be used to summarize HPV vaccine-type-specific seroconversion rates at 6- and 12-months post-transplantation stratified by number of doses (1, 2, or 3) of the vaccine given pre-transplant. Seroconversion probabilities will be compared between dose groups using Fisher's exact test. Armitage trend test will be used to examine whether there is a trend for increased seropositivity across dose groups.

Uterine Cervical Neoplasms

Patients receive one dose of Gardasil 9 IM.

Patients receive one dose of Cervarix IM.

Diphtheria Toxoid/Tetanus Toxoid/Acellular Pertussis Vaccine Adsorbed

Recombinant Human Papillomavirus Bivalent Vaccine

Aimee R Kreimer

This phase IV trial tests whether a single dose of the human papillomavirus (HPV) vaccine works in preventing cervical cancer in young women in Costa Rica. Human papilloma viruses, called HPV, are a group of viruses that very frequently cause infection in both men and women, mainly in the genital organs. There are many types of HPV, and some can cause cancer. The World Health Organization recommends a two-dose schedule for adolescents 9-14 and three doses for individuals 15 years old or older. This study examines whether a single dose of HPV vaccine can reduce the frequency with which women between ages 18-30 become infected with HPV.

PRIMARY OBJECTIVES:

I. To evaluate one dose of nonavalent human papillomavirus (HPV) vaccination compared to no vaccination in the protection against incident HPV16/18 cervical HPV infections that persist 6-months or more in women aged 18 to 30 years who are cervical HPV16/18 deoxyribonucleic acid (DNA) negative prior to and at the time of vaccination.

II. To evaluate one dose of bivalent HPV vaccination compared to no vaccination in the protection against incident HPV16/18 cervical HPV infections that persist 6-months or more in women aged 18 to 30 years who are cervical HPV16/18 DNA negative prior to and at the time of vaccination.

SECONDARY OBJECTIVES:

I. To quantitate the benefit of one dose of HPV vaccination compared to no vaccination in the protection against incident HPV16/18 cervical HPV infections that persist 6-months or more in women aged 18 to 30 years regardless of cervical HPV DNA status at the time of vaccination.

II. To estimate the health impact of older-age single-dose HPV vaccination by modeling the number of cervical cancer cases prevented as well as the cost-effectiveness of cervical cancer prevention strategies incorporating vaccination and screening in Costa Rica.

III. To evaluate the immunogenicity (absolute levels and stability of serum antibodies) of single dose HPV vaccination in women.

IV. For each vaccine separately, to evaluate one dose of HPV vaccination compared to no vaccination in the protection against:

IVa. Any new HPV16/18 anal infection that persists 6+ months. IVb. Any new HPV16/18 oral infection that persists 6+ months. IVc. Any new carcinogenic HPV cervical, anal or oral infection detected at a single timepoint and that persists 6+ months.

IVd. Any new cervical HPV6/11 infection that persists 6+ months.

OUTLINE: Patients are randomized to 1 of 3 arms.

ARM I: Patients receive one dose of recombinant human papillomavirus nonavalent vaccine (Gardasil 9) intramuscularly (IM).

ARM II: Patients receive one dose of recombinant human papillomavirus bivalent vaccine (Cervarix) IM.

ARM III: Patients receive one dose of diphtheria toxoid/tetanus toxoid/acellular pertussis vaccine adsorbed vaccine (Adacel) IM.

After completion of study, patients are followed up at 6 and 12 months, and then every 6 months thereafter.

Single-Dose HPV Vaccination for the Prevention of Cervical Cancer in Young Adult Women in Costa Rica, The PRISMA ESCUDDO Trial

Single-Dose HPV Vaccination Among Young Adult Women in Costa Rica: the PRISMA-ESCUDDO Trial (PRevencIón Del Cáncer Cervical Con Una Sola Dosis de Vacuna Contra VPH en Mujeres Adultas Jóvenes)

Will estimate the rate of incident persistent infections (i.e. the primary endpoint defined above) in each of the three arms of an ATP cohort and then estimate the two Vaccine Efficacies (VE), comparing each HPV vaccine arm against the control arm. Will require a one-sided p-value of \< 0.0125 for statistical significance. The 97.5% confidence intervals for the VE will be calculated by inverting appropriate hypotheses tests.

Will require a one-sided p-value of \< 0.0125 for statistical significance. The 97.5% confidence intervals for the VE will be calculated by inverting appropriate hypotheses tests.

Will report the Geometric Mean Titer (GMT) of the antibodies for each HPV type at the five follow-up visits.

Will report the VE against any new carcinogenic HPV type and against HPV 6/11 in the according to protocol (ATP) cohort using an analysis plan similar to that described for the primary objectives.

Immune System Diseases

Rare Diseases

Acquired Immunodeficiency Syndrome

HIV Infections

Squamous Intraepithelial Lesions of the Cervix

Uterine Cervical Dysplasia

Precancerous Conditions

Uterine Cervical Diseases

Uterine Diseases

Genital Diseases, Female

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Cervical Intraepithelial Neoplasia

Patients receive Recombinant Human Papillomavirus Nonavalent Vaccine (Gardasil 9) IM at baseline, 4, and 26 weeks in the absence of disease progression or unacceptable toxicity, with sample collection for Laboratory Biomarker Analysis.

Patients receive saline placebo vaccine IM at baseline, 4, and 26 weeks, with sample collection for Laboratory Biomarker Analysis.

Laboratory Biomarker Analysis

Carla Chibwesha

This randomized phase III trial studies how well human papillomavirus (HPV) vaccine therapy works in reducing high-grade cervical lesions in patients with human immunodeficiency virus (HIV) and HPV. Vaccines made from HPV peptides or antigens may help the body build an effective immune response to kill the HPV virus and prevent cervical lesions from developing or coming back after being removed.

At screening, potential participants will be tested for cervical human papillomavirus (HPV) infection (GeneXpert hrHPV assay and HPV DNA PCR) and undergo cervical colposcopy to confirm the absence of cervical cancer. If eligible, the participant will be randomized to receive either the 9-valent HPV vaccine or saline placebo.

Participants will return 4 and 26 weeks later for the second dose of vaccine or placebo. At week 4, participants will have cervical colposcopy and undergo cryotherapy or loop electrosurgical excisional procedure (LEEP) as appropriate. Participants undergoing cervical cryotherapy will have cervical biopsies before the treatment. Participants will be followed with HPV testing (Gene Xpert and HPV DNA PCR) at weeks 26, 52, 78, and 104, and will have cervical cytology and colposcopy with biopsies at weeks 26, 52, and 104.

HPV Vaccine Therapy in Reducing High-Grade Cervical Lesions in Patients With HIV and HPV

A Randomized, Placebo-Controlled Trial of HPV Vaccination to Reduce Cervical High-Grade Squamous Intraepithelial Lesions Among HIV-Infected Women Participating in an HPV Test-and-Treat Program (COVENANT)

Will characterize the HPV type distribution in baseline histology specimens and compare this to the types observed among incident cervical and vulvar HSIL lesions. Specifically, will compare the number and proportion of vaccine-type and non-vaccine type lesions between arms.

For study participants who have the same HPV type in HSIL specimens at baseline and follow-up time points, sequencing will be performed to determine whether or not HSIL is caused by an identical HPV strain. Will use all available pairs of baseline and follow-up HSIL caused by the same HPV type. Will report the proportion of these pairs with the same HPV strain in both treatment arms. Additionally, will report the rates of HSIL caused by new vaccine type infections. We will compare the two study groups using a chi-square test. This will be a descriptive analysis only as no sufficient data on which to power this analysis.

Specimen banking objective. There is no pre-specified statistical analysis plan for this objective. Any future studies using these specimens will need to receive separate approval by NCI and CTEP.

McNemar's chi-square test to compare the prevalence of that type in the anus and cervix will be used. For each hrHPV type, chi-square analyses will be used to compare the two HPV vaccination groups with respect to the distribution of that type in the (anus, cervix). Will report the proportion of incident cervical infections that were preceded by anal detection of the same type.

Will explore the antibody titers for the vaccine type found in the HSIL in these women as compared to those without HSIL caused by that type. Analysis of vaccine titers between those with incident vaccine type HPV infections that persist for 2 or more study visits and those that do not will be performed.

For each arm (vaccine and placebo), the event rate will be estimated using its point estimate and 95% Poisson confidence intervals. Poisson regression analyses will be used to compare the two arms with respect to event rate. In addition, time to event from week 4 to 52 will be described using the Kaplan-Meier method for each arm, and the two arms will be compared with respect to time to event using the log-rank test.

The event rate for each arm from week 52 to week 104 for women who are event-free at 52 weeks will be estimated using its point estimate and 95% Poisson confidence interval. Poisson regression will be used to compare the two groups with respect to the event rate from week 52 to 104.

Poisson regression analyses will be used to determine if baseline HPV types are associated with of sustained absence of cervical HSIL and clearance of HPV infections after cryotherapy or LEEP. This analysis will also control for use of LEEP or cryotherapy.

Poisson regression analyses will be used to determine if the presence of HSIL at baseline is associated with of sustained absence of cervical HSIL and clearance of HPV infections after cryotherapy or LEEP. This analysis will also control for use of LEEP or cryotherapy.

Poisson regression analyses will be used to determine if baseline CD4+ cell count is associated with of sustained absence of cervical HSIL and clearance of HPV infections after cryotherapy or LEEP. This analysis will also control for use of LEEP or cryotherapy.

Poisson regression analyses will be used to determine if baseline plasma HIV-1 RNA count is associated with of sustained absence of cervical HSIL and clearance of HPV infections after cryotherapy or LEEP. This analysis will also control for use of LEEP or cryotherapy.

Poisson regression analyses will be used to determine if ART use is associated with of sustained absence of cervical HSIL and clearance of HPV infections after cryotherapy or LEEP. This analysis will also control for use of LEEP or cryotherapy.

Poisson regression analyses will be used to determine if age is associated with of sustained absence of cervical HSIL and clearance of HPV infections after cryotherapy or LEEP. This analysis will also control for use of LEEP or cryotherapy.

Poisson regression analyses will be used to determine if sexual behavior is associated with of sustained absence of cervical HSIL and clearance of HPV infections after cryotherapy or LEEP. This analysis will also control for use of LEEP or cryotherapy.

Poisson regression analyses will be used to determine if vaccine use is associated with of sustained absence of cervical HSIL and clearance of HPV infections after cryotherapy or LEEP. This analysis will also control for use of LEEP or cryotherapy.

Vaccine and placebo participants will be compared with respect to these proportions using the chi-square test corrected for continuity.

The proportion of women with abnormal cervical cytology at baseline, week 26, 52, and 104 will be reported and compared between arms.

The prevalence of vulvar HSIL or cancer at baseline will be estimated using the binomial proportion and its 95% confidence interval.

The proportion of women who acquire vulvar HSIL or cancer among those negative for vulvar HSIL or cancer at baseline for both intervention arms will be estimated as a binomial proportion for both groups. The chi-square test corrected for continuity will be used to compare arms with respect to the proportions who acquire vulvar HSIL during the study.

Logistic regression analyses will be used to evaluate associations with incident vulvar HSIL or cancer acquisition with clinical and demographic factors and arm.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Testing RG1-VLP Vaccine to Prevent HPV-related Cancers	NCT05985681	Human Papilloma...	Biospecimen Col... HPV16 RG1 VLP V... Questionnaire A... Recombinant Hum... Saline	18 Years - 45 Years	National Cancer Institute (NCI)
Gardasil 9 Vaccine in Preventing HPV Infection in Patients With Hematologic Malignancies Undergoing Donor Stem Cell Transplant	NCT03023631	Allogeneic Hema... Hematopoietic a...	Recombinant Hum...	18 Years -	M.D. Anderson Cancer Center
Preventive Human Papillomavirus (HPV) Vaccine Trial in Kidney Transplant Recipients	NCT03036930	Human Papilloma...	Biospecimen Col... HPV Self-Collec... Questionnaire A... Recombinant Hum...	18 Years - 49 Years	National Cancer Institute (NCI)
Single-Dose HPV Vaccination for the Prevention of Cervical Cancer in Young Adult Women in Costa Rica, The PRISMA ESCUDDO Trial	NCT05237947	Cervical Carcin... Human Papilloma...	Diphtheria Toxo... Questionnaire A... Recombinant Hum... Recombinant Hum...	18 Years - 30 Years	National Cancer Institute (NCI)
HPV Vaccine Therapy in Reducing High-Grade Cervical Lesions in Patients With HIV and HPV	NCT03284866	AIDS-Related Hu... High Grade Cerv... HIV Infection	Laboratory Biom... Recombinant Hum... Saline	25 Years -	AIDS Malignancy Consortium
Testing RG1-VLP Vaccine to Prevent HPV-related Cancers	NCT05985681	Human Papilloma...	Biospecimen Col... HPV16 RG1 VLP V... Questionnaire A... Recombinant Hum... Saline	18 Years - 45 Years	National Cancer Institute (NCI)
Testing RG1-VLP Vaccine to Prevent HPV-related Cancers	NCT05985681	Human Papilloma...	Biospecimen Col... HPV16 RG1 VLP V... Questionnaire A... Recombinant Hum... Saline	18 Years - 45 Years	National Cancer Institute (NCI)
Testing RG1-VLP Vaccine to Prevent HPV-related Cancers	NCT05985681	Human Papilloma...	Biospecimen Col... HPV16 RG1 VLP V... Questionnaire A... Recombinant Hum... Saline	18 Years - 45 Years	National Cancer Institute (NCI)

Spots Global Cancer Trial Database for recombinant human papillomavirus nonavalent vaccine