High Grade Anal Canal Intraepithelial Neoplasia, High Grade Vulvar Squamous Intraepithelial Lesion
Conditions
Brief summary
This phase IV trial studies how well human papillomavirus (HPV) vaccine therapy works in interrupting progression in patients with high-grade vulvar or anal lesions. Vaccines made from HPV peptides or antigens may help the body build an effective immune response to kill tumor cells and decrease the chance of vulvar or anal lesions to progress or come back.
Detailed description
OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive recombinant human papillomavirus nonavalent vaccine intramuscularly (IM) at baseline, 2 months, and 6 months. ARM II: Patients receive placebo IM at baseline, 2 months, and 6 months. After completion of study treatment, patients are followed up at months 7, 12, 18, 24, 36, and 42.
Interventions
OTHERLaboratory Biomarker Analysis
Correlative studies
OTHERPlacebo Administration
Given IM
OTHERQuestionnaire Administration
Ancillary studies
Given IM
Sponsors
National Cancer Institute (NCI)
Fred Hutchinson Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
27 Years to 69 Years
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed diagnosis of initial or recurrent anal or vulvar high-grade squamous intraepithelial lesion (AIN2/3 or VIN2/3) diagnosed on or after 1/1/2014; study pathologist will use p16 staining as needed to rule out low-grade squamous intraepithelial lesion (LSIL) disease * \>= 2 months since last therapy for HSIL * No clinical evidence of HSIL on screening examination; if HSIL is suspected, a biopsy will be done to exclude HSIL; patients whose screening visit reveals HSIL on biopsy, may be re-screened \>= 2 months after therapy * Resident in the catchment area of the clinics and willing to attend up to 8 clinic visits for a 36-month period * Sexually active women of child-bearing potential must be willing to use effective contraception through month 7 of the study * If human immunodeficiency virus (HIV) positive, receipt of anti-retroviral therapy continuously for at least 6 months prior to enrollment * Ability to give informed consent * Willingness to sign medical records release form and tissue release form
Exclusion criteria
* Currently pregnant * Chemotherapy (current, within the last month, or anticipated in the next 7 months) * Prior history of invasive HPV-related anogenital cancer (cervical, vaginal, vulvar, penile, or anal cancer), or oropharyngeal cancer (base of tongue, tonsil); prior cancer at other sites (including most of oral cavity) or larynx are not exclusions * Unstable medical condition (e.g., another malignancy requiring treatment, malignant hypertension, poorly controlled diabetes, another cancer except for fully excised non-melanoma skin cancer) * Prior HPV vaccination * Known allergy or intolerance to lidocaine * Currently participating in an interventional research study related to HPV, except the Anal Cancer HSIL Outcomes Research (ANCHOR) study (NCT02135419) * Any other condition which, in the opinion of the investigator, may compromise the subject's ability to follow study procedures and safely complete the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Persistent High-risk Infection Among Vaccine Compared With Placebo Recipients | Up to month 36 | Persistence will be measured as two or more consecutive polymerase chain reaction (PCR) positive swabs for the same human papillomavirus (HPV) genotype. Will use Chi-Square test to compare the number of participants with the persistent infection in the vaccinated to unvaccinated group. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Recurrence of Anogenital High Grade Squamous Intraepithelial Lesion (HSIL) | Up to month 36 | Will compare vaccine and placebo recipients. Will evaluate differences in the hazard of recurrence using Cox proportional hazards in the intention to treat population and the per protocol population. |
| Incidence of Adverse Events (AEs) Via Solicited Vaccine Reactogenicity by Arm | Up to month 36 | Will monitor safety by comparing type and frequency of AEs in the two study arms, graded according to the Food and Drug Administration criteria. Symptoms are reported at least once from any dose. |
| HPV Antibody Level | Up to month 36 | Will evaluate placebo and vaccine recipients separately. Will assess whether presence and amount of HPV antibody, detected at baseline in the placebo arm, is protective against recurrence. For the vaccine arm, will assess whether magnitude of vaccine antibody levels month 1 following the third vaccination in the vaccine arm affects recurrence. |
Countries
United States
Participant flow
Recruitment details
Study recruitment was open between August 2017 and December 2021. Potential participants were recruited through the Fred Hutchinson Cancer Surveillance System and referral by local healthcare providers. Screening took place via phone interviews and in-person visits at the study clinics. Enrollment took place at the two study clinics: Virology Research Center at the University of Washington, and the Center for Women's Reproductive Health at the University of Alabama Birmingham.
Participants by arm
| Arm | Count |
|---|---|
| Arm I (Recombinant Human Papillomavirus Nonavalent Vaccine) Patients receive recombinant human papillomavirus nonavalent vaccine IM at baseline, 2 months, and 6 months.
Laboratory Biomarker Analysis: Correlative studies
Questionnaire Administration: Ancillary studies
Recombinant Human Papillomavirus Nonavalent Vaccine: Given IM | 91 |
| Arm II (Placebo) Patients receive placebo IM at baseline, 2 months, and 6 months.
Laboratory Biomarker Analysis: Correlative studies
Placebo Administration: Given IM
Questionnaire Administration: Ancillary studies | 94 |
| Total | 185 |
Baseline characteristics
| Characteristic | Arm I (Recombinant Human Papillomavirus Nonavalent Vaccine) | Arm II (Placebo) | Total |
|---|---|---|---|
| Age, Continuous | 53 years | 57 years | 55 years |
| Anatomic Site of HSIL (high-grade squamous intraepithelial lesion) Anal | 50 Participants | 53 Participants | 103 Participants |
| Anatomic Site of HSIL (high-grade squamous intraepithelial lesion) Vulvar | 41 Participants | 41 Participants | 82 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 3 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 84 Participants | 89 Participants | 173 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 2 Participants | 4 Participants |
| HIV Status HIV Negative | 59 Participants | 55 Participants | 114 Participants |
| HIV Status HIV Positive | 32 Participants | 39 Participants | 71 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 9 Participants | 6 Participants | 15 Participants |
| Race (NIH/OMB) More than one race | 5 Participants | 7 Participants | 12 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 3 Participants | 7 Participants |
| Race (NIH/OMB) White | 70 Participants | 75 Participants | 145 Participants |
| Region of Enrollment United States | 91 participants | 94 participants | 185 participants |
| Sex/Gender, Customized Men | 41 participants | 44 participants | 85 participants |
| Sex/Gender, Customized Transgender women | 1 participants | 0 participants | 1 participants |
| Sex/Gender, Customized Women | 49 participants | 50 participants | 99 participants |
| Smoking Status Current | 20 Participants | 18 Participants | 38 Participants |
| Smoking Status Former | 31 Participants | 24 Participants | 55 Participants |
| Smoking Status Never | 40 Participants | 52 Participants | 92 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 5 / 91 | 2 / 94 |
| other Total, other adverse events | 60 / 91 | 58 / 94 |
| serious Total, serious adverse events | 19 / 91 | 16 / 94 |
Outcome results
Primary
Persistent High-risk Infection Among Vaccine Compared With Placebo Recipients
Persistence will be measured as two or more consecutive polymerase chain reaction (PCR) positive swabs for the same human papillomavirus (HPV) genotype. Will use Chi-Square test to compare the number of participants with the persistent infection in the vaccinated to unvaccinated group.
Time frame: Up to month 36
Population: Participants were included in this analysis if they had 2 or more HPV DNA PCR results from swabs collected after the baseline swab. Of the 185 participants in the baseline population, 117 were included in this analysis.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm I (Recombinant Human Papillomavirus Nonavalent Vaccine) | Persistent High-risk Infection Among Vaccine Compared With Placebo Recipients | HPV16 persistence identified | 7 Participants |
| Arm I (Recombinant Human Papillomavirus Nonavalent Vaccine) | Persistent High-risk Infection Among Vaccine Compared With Placebo Recipients | HPV18/45 persistence identified | 3 Participants |
| Arm I (Recombinant Human Papillomavirus Nonavalent Vaccine) | Persistent High-risk Infection Among Vaccine Compared With Placebo Recipients | HPV31/33/52/58 persistence identified | 3 Participants |
| Arm I (Recombinant Human Papillomavirus Nonavalent Vaccine) | Persistent High-risk Infection Among Vaccine Compared With Placebo Recipients | HPV33/39/51/56/59 persistence identified | 4 Participants |
| Arm I (Recombinant Human Papillomavirus Nonavalent Vaccine) | Persistent High-risk Infection Among Vaccine Compared With Placebo Recipients | Overall high-risk HPV persistence identified | 13 Participants |
| Arm I (Recombinant Human Papillomavirus Nonavalent Vaccine) | Persistent High-risk Infection Among Vaccine Compared With Placebo Recipients | High-risk HPV persistence NOT identified | 23 Participants |
| Arm II (Placebo) | Persistent High-risk Infection Among Vaccine Compared With Placebo Recipients | Overall high-risk HPV persistence identified | 21 Participants |
| Arm II (Placebo) | Persistent High-risk Infection Among Vaccine Compared With Placebo Recipients | HPV16 persistence identified | 9 Participants |
| Arm II (Placebo) | Persistent High-risk Infection Among Vaccine Compared With Placebo Recipients | HPV33/39/51/56/59 persistence identified | 8 Participants |
| Arm II (Placebo) | Persistent High-risk Infection Among Vaccine Compared With Placebo Recipients | HPV18/45 persistence identified | 5 Participants |
| Arm II (Placebo) | Persistent High-risk Infection Among Vaccine Compared With Placebo Recipients | High-risk HPV persistence NOT identified | 10 Participants |
| Arm II (Placebo) | Persistent High-risk Infection Among Vaccine Compared With Placebo Recipients | HPV31/33/52/58 persistence identified | 11 Participants |
Comparison: This p-value compares HPV16 persistence by study arm.p-value: 0.89Chi-squared
Comparison: This p-value compares HPV18/45 persistence by study arm.p-value: 0.65Chi-squared
Comparison: This p-value compares HPV31/33/52/58 persistence by study arm.p-value: 0.056Chi-squared
Comparison: This p-value compares HPV35/39/51/56/59 persistence by study arm.p-value: 0.38Chi-squared
p-value: 0.33Chi-squared
Secondary
HPV Antibody Level
Will evaluate placebo and vaccine recipients separately. Will assess whether presence and amount of HPV antibody, detected at baseline in the placebo arm, is protective against recurrence. For the vaccine arm, will assess whether magnitude of vaccine antibody levels month 1 following the third vaccination in the vaccine arm affects recurrence.
Time frame: Up to month 36
Population: Participants with usable serology samples from at least one timepoint are included in this analysis.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Arm I (Recombinant Human Papillomavirus Nonavalent Vaccine) | HPV Antibody Level | HPV16 | Positive, HSIL | 5 Participants |
| Arm I (Recombinant Human Papillomavirus Nonavalent Vaccine) | HPV Antibody Level | HPV18 | Negative, No event | 32 Participants |
| Arm I (Recombinant Human Papillomavirus Nonavalent Vaccine) | HPV Antibody Level | HPV16 | Negative, No event | 33 Participants |
| Arm I (Recombinant Human Papillomavirus Nonavalent Vaccine) | HPV Antibody Level | HPV16 | Positive, no event | 22 Participants |
| Arm I (Recombinant Human Papillomavirus Nonavalent Vaccine) | HPV Antibody Level | HPV16 | Negative, HSIL | 8 Participants |
| Arm I (Recombinant Human Papillomavirus Nonavalent Vaccine) | HPV Antibody Level | HPV18 | Positive, no event | 23 Participants |
| Arm I (Recombinant Human Papillomavirus Nonavalent Vaccine) | HPV Antibody Level | HPV18 | Negative, HSIL | 7 Participants |
| Arm I (Recombinant Human Papillomavirus Nonavalent Vaccine) | HPV Antibody Level | HPV18 | Positive, HSIL | 6 Participants |
| Arm I (Recombinant Human Papillomavirus Nonavalent Vaccine) | HPV Antibody Level | HPV31 | Negative, No event | 28 Participants |
| Arm I (Recombinant Human Papillomavirus Nonavalent Vaccine) | HPV Antibody Level | HPV31 | Positive, no event | 27 Participants |
| Arm I (Recombinant Human Papillomavirus Nonavalent Vaccine) | HPV Antibody Level | HPV31 | Negative, HSIL | 8 Participants |
| Arm I (Recombinant Human Papillomavirus Nonavalent Vaccine) | HPV Antibody Level | HPV31 | Positive, HSIL | 5 Participants |
| Arm I (Recombinant Human Papillomavirus Nonavalent Vaccine) | HPV Antibody Level | HPV33 | Negative, No event | 30 Participants |
| Arm I (Recombinant Human Papillomavirus Nonavalent Vaccine) | HPV Antibody Level | HPV33 | Positive, no event | 25 Participants |
| Arm I (Recombinant Human Papillomavirus Nonavalent Vaccine) | HPV Antibody Level | HPV33 | Negative, HSIL | 8 Participants |
| Arm I (Recombinant Human Papillomavirus Nonavalent Vaccine) | HPV Antibody Level | HPV33 | Positive, HSIL | 5 Participants |
| Arm I (Recombinant Human Papillomavirus Nonavalent Vaccine) | HPV Antibody Level | HPV45 | Negative, No event | 33 Participants |
| Arm I (Recombinant Human Papillomavirus Nonavalent Vaccine) | HPV Antibody Level | HPV45 | Positive, no event | 22 Participants |
| Arm I (Recombinant Human Papillomavirus Nonavalent Vaccine) | HPV Antibody Level | HPV45 | Negative, HSIL | 8 Participants |
| Arm I (Recombinant Human Papillomavirus Nonavalent Vaccine) | HPV Antibody Level | HPV45 | Positive, HSIL | 5 Participants |
| Arm I (Recombinant Human Papillomavirus Nonavalent Vaccine) | HPV Antibody Level | HPV52 | Negative, No event | 27 Participants |
| Arm I (Recombinant Human Papillomavirus Nonavalent Vaccine) | HPV Antibody Level | HPV52 | Positive, no event | 28 Participants |
| Arm I (Recombinant Human Papillomavirus Nonavalent Vaccine) | HPV Antibody Level | HPV52 | Negative, HSIL | 7 Participants |
| Arm I (Recombinant Human Papillomavirus Nonavalent Vaccine) | HPV Antibody Level | HPV52 | Positive, HSIL | 6 Participants |
| Arm I (Recombinant Human Papillomavirus Nonavalent Vaccine) | HPV Antibody Level | HPV58 | Negative, No event | 28 Participants |
| Arm I (Recombinant Human Papillomavirus Nonavalent Vaccine) | HPV Antibody Level | HPV58 | Positive, no event | 27 Participants |
| Arm I (Recombinant Human Papillomavirus Nonavalent Vaccine) | HPV Antibody Level | HPV58 | Negative, HSIL | 7 Participants |
| Arm I (Recombinant Human Papillomavirus Nonavalent Vaccine) | HPV Antibody Level | HPV58 | Positive, HSIL | 6 Participants |
| Arm I (Recombinant Human Papillomavirus Nonavalent Vaccine) | HPV Antibody Level | Any HPV | Negative, No event | 16 Participants |
| Arm I (Recombinant Human Papillomavirus Nonavalent Vaccine) | HPV Antibody Level | Any HPV | Positive, no event | 39 Participants |
| Arm I (Recombinant Human Papillomavirus Nonavalent Vaccine) | HPV Antibody Level | Any HPV | Negative, HSIL | 4 Participants |
| Arm I (Recombinant Human Papillomavirus Nonavalent Vaccine) | HPV Antibody Level | Any HPV | Positive, HSIL | 9 Participants |
| Arm II (Placebo) | HPV Antibody Level | Any HPV | Positive, HSIL | 12 Participants |
| Arm II (Placebo) | HPV Antibody Level | HPV16 | Positive, HSIL | 6 Participants |
| Arm II (Placebo) | HPV Antibody Level | HPV45 | Negative, No event | 41 Participants |
| Arm II (Placebo) | HPV Antibody Level | HPV58 | Negative, No event | 44 Participants |
| Arm II (Placebo) | HPV Antibody Level | HPV16 | Negative, No event | 49 Participants |
| Arm II (Placebo) | HPV Antibody Level | HPV45 | Positive, no event | 21 Participants |
| Arm II (Placebo) | HPV Antibody Level | HPV16 | Positive, no event | 13 Participants |
| Arm II (Placebo) | HPV Antibody Level | Any HPV | Negative, No event | 20 Participants |
| Arm II (Placebo) | HPV Antibody Level | HPV16 | Negative, HSIL | 12 Participants |
| Arm II (Placebo) | HPV Antibody Level | HPV18 | Negative, No event | 48 Participants |
| Arm II (Placebo) | HPV Antibody Level | HPV45 | Negative, HSIL | 16 Participants |
| Arm II (Placebo) | HPV Antibody Level | HPV18 | Positive, no event | 14 Participants |
| Arm II (Placebo) | HPV Antibody Level | HPV58 | Positive, no event | 18 Participants |
| Arm II (Placebo) | HPV Antibody Level | HPV18 | Negative, HSIL | 12 Participants |
| Arm II (Placebo) | HPV Antibody Level | HPV45 | Positive, HSIL | 2 Participants |
| Arm II (Placebo) | HPV Antibody Level | HPV18 | Positive, HSIL | 6 Participants |
| Arm II (Placebo) | HPV Antibody Level | Any HPV | Negative, HSIL | 6 Participants |
| Arm II (Placebo) | HPV Antibody Level | HPV31 | Negative, No event | 48 Participants |
| Arm II (Placebo) | HPV Antibody Level | HPV52 | Negative, No event | 42 Participants |
| Arm II (Placebo) | HPV Antibody Level | HPV31 | Positive, no event | 14 Participants |
| Arm II (Placebo) | HPV Antibody Level | HPV58 | Negative, HSIL | 13 Participants |
| Arm II (Placebo) | HPV Antibody Level | HPV31 | Negative, HSIL | 13 Participants |
| Arm II (Placebo) | HPV Antibody Level | HPV52 | Positive, no event | 20 Participants |
| Arm II (Placebo) | HPV Antibody Level | HPV31 | Positive, HSIL | 5 Participants |
| Arm II (Placebo) | HPV Antibody Level | Any HPV | Positive, no event | 42 Participants |
| Arm II (Placebo) | HPV Antibody Level | HPV33 | Negative, No event | 47 Participants |
| Arm II (Placebo) | HPV Antibody Level | HPV52 | Negative, HSIL | 14 Participants |
| Arm II (Placebo) | HPV Antibody Level | HPV33 | Positive, no event | 15 Participants |
| Arm II (Placebo) | HPV Antibody Level | HPV58 | Positive, HSIL | 5 Participants |
| Arm II (Placebo) | HPV Antibody Level | HPV33 | Negative, HSIL | 15 Participants |
| Arm II (Placebo) | HPV Antibody Level | HPV52 | Positive, HSIL | 4 Participants |
| Arm II (Placebo) | HPV Antibody Level | HPV33 | Positive, HSIL | 3 Participants |
Comparison: This p-value compares HSIL recurrence and presence of HPV16, in Arm I (Vaccine)p-value: 0.93Log Rank
Comparison: This p-value compares HSIL recurrence and presence of HPV18, in Arm I (Vaccine)p-value: 0.77Log Rank
Comparison: This p-value compares HSIL recurrence and presence of HPV31, in Arm I (Vaccine)p-value: 0.57Log Rank
Comparison: This p-value compares HSIL recurrence and presence of HPV33, in Arm I (Vaccine)p-value: 0.73Log Rank
Comparison: This p-value compares HSIL recurrence and presence of HPV45, in Arm I (Vaccine)p-value: 0.998Log Rank
Comparison: This p-value compares HSIL recurrence and presence of HPV52, in Arm I (Vaccine)p-value: 0.93Log Rank
Comparison: This p-value compares HSIL recurrence and presence of HPV58, in Arm I (Vaccine)p-value: 0.95Log Rank
Comparison: This p-value compares HSIL recurrence and presence of any HPV type, in Arm I (Vaccine)p-value: 0.91Log Rank
Comparison: This p-value compares HSIL recurrence and presence of HPV16, in Arm II (Placebo)p-value: 0.22Log Rank
Comparison: This p-value compares HSIL recurrence and presence of HPV18, in Arm II (Placebo)p-value: 0.27Log Rank
Comparison: This p-value compares HSIL recurrence and presence of HPV31, in Arm II (Placebo)p-value: 0.72Log Rank
Comparison: This p-value compares HSIL recurrence and presence of HPV33, in Arm II (Placebo)p-value: 0.71Log Rank
Comparison: This p-value compares HSIL recurrence and presence of HPV45, in Arm II (Placebo)p-value: 0.11Log Rank
Comparison: This p-value compares HSIL recurrence and presence of HPV52, in Arm II (Placebo)p-value: 0.58Log Rank
Comparison: This p-value compares HSIL recurrence and presence of HPV58, in Arm II (Placebo)p-value: 0.81Log Rank
Comparison: This p-value compares HSIL recurrence and presence of any HPV type, in Arm II (Placebo)p-value: 0.73Log Rank
Secondary
Incidence of Adverse Events (AEs) Via Solicited Vaccine Reactogenicity by Arm
Will monitor safety by comparing type and frequency of AEs in the two study arms, graded according to the Food and Drug Administration criteria. Symptoms are reported at least once from any dose.
Time frame: Up to month 36
Population: There were 173 incidence of reported symptoms among participants in Arm I (Vaccine) and 127 incidence of reported symptoms among participants in Arm II (Placebo). Overall, there were 91 participants in Arm I (Vaccine) and 94 participants in Arm II (Placebo) reported symptoms at least once for any dose received.
| Arm | Measure | Category | Value (COUNT_OF_UNITS) |
|---|---|---|---|
| Arm I (Recombinant Human Papillomavirus Nonavalent Vaccine) | Incidence of Adverse Events (AEs) Via Solicited Vaccine Reactogenicity by Arm | Fever or chills | 6 Symptom reports |
| Arm I (Recombinant Human Papillomavirus Nonavalent Vaccine) | Incidence of Adverse Events (AEs) Via Solicited Vaccine Reactogenicity by Arm | Headache | 24 Symptom reports |
| Arm I (Recombinant Human Papillomavirus Nonavalent Vaccine) | Incidence of Adverse Events (AEs) Via Solicited Vaccine Reactogenicity by Arm | Fatigue | 23 Symptom reports |
| Arm I (Recombinant Human Papillomavirus Nonavalent Vaccine) | Incidence of Adverse Events (AEs) Via Solicited Vaccine Reactogenicity by Arm | Muscle aches | 17 Symptom reports |
| Arm I (Recombinant Human Papillomavirus Nonavalent Vaccine) | Incidence of Adverse Events (AEs) Via Solicited Vaccine Reactogenicity by Arm | Pain at injection site | 33 Symptom reports |
| Arm I (Recombinant Human Papillomavirus Nonavalent Vaccine) | Incidence of Adverse Events (AEs) Via Solicited Vaccine Reactogenicity by Arm | Tenderness at injection site | 53 Symptom reports |
| Arm I (Recombinant Human Papillomavirus Nonavalent Vaccine) | Incidence of Adverse Events (AEs) Via Solicited Vaccine Reactogenicity by Arm | Swelling at injection site | 12 Symptom reports |
| Arm I (Recombinant Human Papillomavirus Nonavalent Vaccine) | Incidence of Adverse Events (AEs) Via Solicited Vaccine Reactogenicity by Arm | Medical attention/medication | 5 Symptom reports |
| Arm II (Placebo) | Incidence of Adverse Events (AEs) Via Solicited Vaccine Reactogenicity by Arm | Medical attention/medication | 11 Symptom reports |
| Arm II (Placebo) | Incidence of Adverse Events (AEs) Via Solicited Vaccine Reactogenicity by Arm | Fever or chills | 2 Symptom reports |
| Arm II (Placebo) | Incidence of Adverse Events (AEs) Via Solicited Vaccine Reactogenicity by Arm | Pain at injection site | 17 Symptom reports |
| Arm II (Placebo) | Incidence of Adverse Events (AEs) Via Solicited Vaccine Reactogenicity by Arm | Headache | 22 Symptom reports |
| Arm II (Placebo) | Incidence of Adverse Events (AEs) Via Solicited Vaccine Reactogenicity by Arm | Swelling at injection site | 2 Symptom reports |
| Arm II (Placebo) | Incidence of Adverse Events (AEs) Via Solicited Vaccine Reactogenicity by Arm | Fatigue | 25 Symptom reports |
| Arm II (Placebo) | Incidence of Adverse Events (AEs) Via Solicited Vaccine Reactogenicity by Arm | Tenderness at injection site | 31 Symptom reports |
| Arm II (Placebo) | Incidence of Adverse Events (AEs) Via Solicited Vaccine Reactogenicity by Arm | Muscle aches | 17 Symptom reports |
Comparison: This comparison is specific to the incidence of fever or chills.p-value: 0.135Chi-squared
Comparison: This comparison is specific to the incidence of headache.p-value: 0.64Chi-squared
Comparison: This comparison is specific to the incidence of fatigue.p-value: 0.838Chi-squared
Comparison: This comparison is specific to the incidence of muscle aches.p-value: 0.917Chi-squared
Comparison: This comparison is specific to the incidence of pain at injection site.p-value: 0.005Chi-squared
Comparison: This comparison is specific to the incidence of tenderness at injection site.p-value: 0.001Chi-squared
Comparison: This comparison is specific to the incidence of swelling at injection site.p-value: 0.004Chi-squared
Comparison: This comparison is specific to the incidence of medical attention/medication required.p-value: 0.133Chi-squared
Secondary
Time to Recurrence of Anogenital High Grade Squamous Intraepithelial Lesion (HSIL)
Will compare vaccine and placebo recipients. Will evaluate differences in the hazard of recurrence using Cox proportional hazards in the intention to treat population and the per protocol population.
Time frame: Up to month 36
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm I (Recombinant Human Papillomavirus Nonavalent Vaccine) | Time to Recurrence of Anogenital High Grade Squamous Intraepithelial Lesion (HSIL) | 8.1 Recurrent events per 100 person-years |
| Arm II (Placebo) | Time to Recurrence of Anogenital High Grade Squamous Intraepithelial Lesion (HSIL) | 10.1 Recurrent events per 100 person-years |
p-value: 0.54Log Rank