Trial Outcomes & Findings for HPV Vaccine Therapy in Interrupting Progression in Patients With High-Grade Vulvar or Anal Lesions (NCT NCT03051516)

Last Updated: 2024-02-28

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE4

Target enrollment

188 participants

Primary outcome timeframe

Up to month 36

Results posted on

2024-02-28

Participant Flow

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.

Participant milestones

Participant milestones
Measure	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	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
Overall Study STARTED	93	95
Overall Study Vaccination 1	93	95
Overall Study Vaccination 2	91	94
Overall Study Vaccination 3	83	90
Overall Study Month 7 Follow-Up	80	87
Overall Study Month 12 Follow-Up	78	81
Overall Study Month 18 Follow-Up	66	75
Overall Study Month 24 Follow-Up	59	70
Overall Study Month 36 Follow-Up	44	53
Overall Study COMPLETED	38	42
Overall Study NOT COMPLETED	55	53

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

HPV Vaccine Therapy in Interrupting Progression in Patients With High-Grade Vulvar or Anal Lesions

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm I (Recombinant Human Papillomavirus Nonavalent Vaccine) n=91 Participants 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	Arm II (Placebo) n=94 Participants Patients receive placebo IM at baseline, 2 months, and 6 months. Laboratory Biomarker Analysis: Correlative studies Placebo Administration: Given IM Questionnaire Administration: Ancillary studies	Total n=185 Participants Total of all reporting groups
Age, Continuous	53 years n=5 Participants	57 years n=7 Participants	55 years n=5 Participants
Sex/Gender, Customized Women	49 participants n=5 Participants	50 participants n=7 Participants	99 participants n=5 Participants
Sex/Gender, Customized Men	41 participants n=5 Participants	44 participants n=7 Participants	85 participants n=5 Participants
Sex/Gender, Customized Transgender women	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	5 Participants n=5 Participants	3 Participants n=7 Participants	8 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	84 Participants n=5 Participants	89 Participants n=7 Participants	173 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	9 Participants n=5 Participants	6 Participants n=7 Participants	15 Participants n=5 Participants
Race (NIH/OMB) White	70 Participants n=5 Participants	75 Participants n=7 Participants	145 Participants n=5 Participants
Race (NIH/OMB) More than one race	5 Participants n=5 Participants	7 Participants n=7 Participants	12 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants
Region of Enrollment United States	91 participants n=5 Participants	94 participants n=7 Participants	185 participants n=5 Participants
Anatomic Site of HSIL (high-grade squamous intraepithelial lesion) Anal	50 Participants n=5 Participants	53 Participants n=7 Participants	103 Participants n=5 Participants
Anatomic Site of HSIL (high-grade squamous intraepithelial lesion) Vulvar	41 Participants n=5 Participants	41 Participants n=7 Participants	82 Participants n=5 Participants
Smoking Status Never	40 Participants n=5 Participants	52 Participants n=7 Participants	92 Participants n=5 Participants
Smoking Status Former	31 Participants n=5 Participants	24 Participants n=7 Participants	55 Participants n=5 Participants
Smoking Status Current	20 Participants n=5 Participants	18 Participants n=7 Participants	38 Participants n=5 Participants
HIV Status HIV Positive	32 Participants n=5 Participants	39 Participants n=7 Participants	71 Participants n=5 Participants
HIV Status HIV Negative	59 Participants n=5 Participants	55 Participants n=7 Participants	114 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Arm I (Recombinant Human Papillomavirus Nonavalent Vaccine) n=53 Participants 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	Arm II (Placebo) n=64 Participants Patients receive placebo IM at baseline, 2 months, and 6 months. Laboratory Biomarker Analysis: Correlative studies Placebo Administration: Given IM Questionnaire Administration: Ancillary studies
Persistent High-risk Infection Among Vaccine Compared With Placebo Recipients HPV16 persistence identified	7 Participants	9 Participants
Persistent High-risk Infection Among Vaccine Compared With Placebo Recipients HPV18/45 persistence identified	3 Participants	5 Participants
Persistent High-risk Infection Among Vaccine Compared With Placebo Recipients HPV31/33/52/58 persistence identified	3 Participants	11 Participants
Persistent High-risk Infection Among Vaccine Compared With Placebo Recipients HPV33/39/51/56/59 persistence identified	4 Participants	8 Participants
Persistent High-risk Infection Among Vaccine Compared With Placebo Recipients Overall high-risk HPV persistence identified	13 Participants	21 Participants
Persistent High-risk Infection Among Vaccine Compared With Placebo Recipients High-risk HPV persistence NOT identified	23 Participants	10 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Arm I (Recombinant Human Papillomavirus Nonavalent Vaccine) n=91 Participants 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	Arm II (Placebo) n=94 Participants Patients receive placebo IM at baseline, 2 months, and 6 months. Laboratory Biomarker Analysis: Correlative studies Placebo Administration: Given IM Questionnaire Administration: Ancillary studies
Time to Recurrence of Anogenital High Grade Squamous Intraepithelial Lesion (HSIL)	8.1 Recurrent events per 100 person-years	10.1 Recurrent events per 100 person-years

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Arm I (Recombinant Human Papillomavirus Nonavalent Vaccine) n=173 Symptom reports 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	Arm II (Placebo) n=127 Symptom reports Patients receive placebo IM at baseline, 2 months, and 6 months. Laboratory Biomarker Analysis: Correlative studies Placebo Administration: Given IM Questionnaire Administration: Ancillary studies
Incidence of Adverse Events (AEs) Via Solicited Vaccine Reactogenicity by Arm Tenderness at injection site	53 Symptom reports	31 Symptom reports
Incidence of Adverse Events (AEs) Via Solicited Vaccine Reactogenicity by Arm Fever or chills	6 Symptom reports	2 Symptom reports
Incidence of Adverse Events (AEs) Via Solicited Vaccine Reactogenicity by Arm Headache	24 Symptom reports	22 Symptom reports
Incidence of Adverse Events (AEs) Via Solicited Vaccine Reactogenicity by Arm Fatigue	23 Symptom reports	25 Symptom reports
Incidence of Adverse Events (AEs) Via Solicited Vaccine Reactogenicity by Arm Pain at injection site	33 Symptom reports	17 Symptom reports
Incidence of Adverse Events (AEs) Via Solicited Vaccine Reactogenicity by Arm Swelling at injection site	12 Symptom reports	2 Symptom reports
Incidence of Adverse Events (AEs) Via Solicited Vaccine Reactogenicity by Arm Medical attention/medication	5 Symptom reports	11 Symptom reports
Incidence of Adverse Events (AEs) Via Solicited Vaccine Reactogenicity by Arm Muscle aches	17 Symptom reports	17 Symptom reports

SECONDARY outcome

Timeframe: Up to month 36

Population: Participants with usable serology samples from at least one timepoint are included in this analysis.

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.

Outcome measures

Outcome measures
Measure	Arm I (Recombinant Human Papillomavirus Nonavalent Vaccine) n=68 Participants 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	Arm II (Placebo) n=80 Participants Patients receive placebo IM at baseline, 2 months, and 6 months. Laboratory Biomarker Analysis: Correlative studies Placebo Administration: Given IM Questionnaire Administration: Ancillary studies
HPV Antibody Level HPV16 · Negative, No event	33 Participants	49 Participants
HPV Antibody Level HPV16 · Positive, no event	22 Participants	13 Participants
HPV Antibody Level HPV16 · Negative, HSIL	8 Participants	12 Participants
HPV Antibody Level HPV16 · Positive, HSIL	5 Participants	6 Participants
HPV Antibody Level HPV18 · Negative, No event	32 Participants	48 Participants
HPV Antibody Level HPV18 · Positive, no event	23 Participants	14 Participants
HPV Antibody Level HPV18 · Negative, HSIL	7 Participants	12 Participants
HPV Antibody Level HPV18 · Positive, HSIL	6 Participants	6 Participants
HPV Antibody Level HPV31 · Negative, No event	28 Participants	48 Participants
HPV Antibody Level HPV31 · Positive, no event	27 Participants	14 Participants
HPV Antibody Level HPV31 · Negative, HSIL	8 Participants	13 Participants
HPV Antibody Level HPV33 · Negative, No event	30 Participants	47 Participants
HPV Antibody Level HPV33 · Positive, no event	25 Participants	15 Participants
HPV Antibody Level HPV33 · Positive, HSIL	5 Participants	3 Participants
HPV Antibody Level HPV45 · Negative, No event	33 Participants	41 Participants
HPV Antibody Level HPV45 · Positive, no event	22 Participants	21 Participants
HPV Antibody Level HPV45 · Negative, HSIL	8 Participants	16 Participants
HPV Antibody Level HPV52 · Negative, No event	27 Participants	42 Participants
HPV Antibody Level HPV52 · Positive, no event	28 Participants	20 Participants
HPV Antibody Level HPV52 · Negative, HSIL	7 Participants	14 Participants
HPV Antibody Level HPV52 · Positive, HSIL	6 Participants	4 Participants
HPV Antibody Level HPV58 · Negative, No event	28 Participants	44 Participants
HPV Antibody Level HPV58 · Positive, no event	27 Participants	18 Participants
HPV Antibody Level HPV58 · Negative, HSIL	7 Participants	13 Participants
HPV Antibody Level HPV58 · Positive, HSIL	6 Participants	5 Participants
HPV Antibody Level Any HPV · Positive, no event	39 Participants	42 Participants
HPV Antibody Level Any HPV · Positive, HSIL	9 Participants	12 Participants
HPV Antibody Level HPV31 · Positive, HSIL	5 Participants	5 Participants
HPV Antibody Level HPV33 · Negative, HSIL	8 Participants	15 Participants
HPV Antibody Level HPV45 · Positive, HSIL	5 Participants	2 Participants
HPV Antibody Level Any HPV · Negative, No event	16 Participants	20 Participants
HPV Antibody Level Any HPV · Negative, HSIL	4 Participants	6 Participants

Adverse Events

Arm I (Recombinant Human Papillomavirus Nonavalent Vaccine)

Serious events: 19 serious events

Other events: 60 other events

Deaths: 5 deaths

Arm II (Placebo)

Serious events: 16 serious events

Other events: 58 other events

Deaths: 2 deaths

Serious adverse events

Other adverse events

Additional Information

Margaret M. Madeleine, PhD

Fred Hutchinson Cancer Center

Phone: 206-667-4630

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Arm I (Recombinant Human Papillomavirus Nonavalent Vaccine) n=91 participants at risk 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	Arm II (Placebo) n=94 participants at risk Patients receive placebo IM at baseline, 2 months, and 6 months. Laboratory Biomarker Analysis: Correlative studies Placebo Administration: Given IM Questionnaire Administration: Ancillary studies
Injury, poisoning and procedural complications Fracture, right femur	1.1% 1/91 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.	0.00% 0/94 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.
Injury, poisoning and procedural complications Fracture, right hip	1.1% 1/91 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.	0.00% 0/94 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.
Injury, poisoning and procedural complications Fracture, right arm	1.1% 1/91 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.	0.00% 0/94 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.
Injury, poisoning and procedural complications Fracture, left leg	1.1% 1/91 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.	0.00% 0/94 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.
Injury, poisoning and procedural complications Fracture, broken neck	1.1% 1/91 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.	0.00% 0/94 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.
Infections and infestations Hospitalization due to multiple abscesses	0.00% 0/91 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.	1.1% 1/94 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.
Renal and urinary disorders Acute kidney injury	0.00% 0/91 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.	1.1% 1/94 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.
Gastrointestinal disorders Small bowel obstruction	0.00% 0/91 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.	1.1% 1/94 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.
Renal and urinary disorders Pyelonephritis	0.00% 0/91 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.	1.1% 1/94 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.
Gastrointestinal disorders Probable gastroenteritis, 3-day hospitalization	0.00% 0/91 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.	1.1% 1/94 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.
Respiratory, thoracic and mediastinal disorders COPD exacerbation	0.00% 0/91 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.	1.1% 1/94 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.
General disorders Severe migraine requiring overnight hospitalization	0.00% 0/91 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.	1.1% 1/94 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	1.1% 1/91 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.	1.1% 1/94 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.
Infections and infestations Death due to COVID-19 related complications	0.00% 0/91 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.	1.1% 1/94 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Invasive lung adenocarcinoma	0.00% 0/91 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.	1.1% 1/94 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) High grade locally advanced squamous cell carcinoma of the bladder	0.00% 0/91 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.	1.1% 1/94 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.
Cardiac disorders Myocardial infarction	1.1% 1/91 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.	1.1% 1/94 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.
Cardiac disorders Angina	0.00% 0/91 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.	1.1% 1/94 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.
Infections and infestations Skin Infection, left arm	0.00% 0/91 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.	1.1% 1/94 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Deceased due to unknown cancer	0.00% 0/91 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.	1.1% 1/94 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) deceased, secondary to metastatic carcinoma	0.00% 0/91 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.	1.1% 1/94 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.
Infections and infestations Cellulitis	1.1% 1/91 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.	0.00% 0/94 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.
Nervous system disorders Coma secondary to fall	1.1% 1/91 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.	0.00% 0/94 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.
Nervous system disorders Ischemic stroke	1.1% 1/91 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.	0.00% 0/94 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.
Infections and infestations Severe sepsis from atypical/viral pneumonia	1.1% 1/91 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.	0.00% 0/94 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.
Infections and infestations Pneumonia requiring inpatient hospitalization and intubation	1.1% 1/91 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.	0.00% 0/94 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.
General disorders Pancreatitis or Gatroenteritis	1.1% 1/91 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.	0.00% 0/94 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.
Infections and infestations Skin and soft tissue infection/abscess secondary to Staph aureus (MRSA)	1.1% 1/91 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.	0.00% 0/94 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.
Endocrine disorders Alcohol-related pancreatitis	1.1% 1/91 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.	0.00% 0/94 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.
Surgical and medical procedures Transurethral resections of the prostate	1.1% 1/91 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.	0.00% 0/94 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.
Surgical and medical procedures Inguinal hernia repair with subsequent urinary retention	1.1% 1/91 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.	0.00% 0/94 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.
Injury, poisoning and procedural complications Motor vehicle accident	1.1% 1/91 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.	0.00% 0/94 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.
Endocrine disorders Acute pancreatitis	1.1% 1/91 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.	0.00% 0/94 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.

Measure	Arm I (Recombinant Human Papillomavirus Nonavalent Vaccine) n=91 participants at risk 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	Arm II (Placebo) n=94 participants at risk Patients receive placebo IM at baseline, 2 months, and 6 months. Laboratory Biomarker Analysis: Correlative studies Placebo Administration: Given IM Questionnaire Administration: Ancillary studies
General disorders Knot on left arm post COVID-19 injection	0.00% 0/91 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.	1.1% 1/94 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.
General disorders Sore arm post COVID-19 injection	0.00% 0/91 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.	1.1% 1/94 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.
General disorders Fatigue post COVID-19 injection	0.00% 0/91 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.	1.1% 1/94 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.
General disorders High fever (101-102 degrees) post COVID-19 injection	0.00% 0/91 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.	1.1% 1/94 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.
General disorders Weakness post COVID-19 injection	0.00% 0/91 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.	1.1% 1/94 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.
General disorders Fatigue	25.3% 23/91 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.	27.7% 26/94 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.
General disorders Throbbing in right big toe	0.00% 0/91 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.	1.1% 1/94 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.
General disorders Throbbing in right collar bone	0.00% 0/91 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.	1.1% 1/94 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.
Pregnancy, puerperium and perinatal conditions Spontaneous abortion	1.1% 1/91 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.	0.00% 0/94 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.
Infections and infestations Fever or chills	6.6% 6/91 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.	8.5% 8/94 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.
General disorders Headache	26.4% 24/91 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.	23.4% 22/94 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.
General disorders Muscle aches	18.7% 17/91 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.	18.1% 17/94 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.
Injury, poisoning and procedural complications Injection site pain	36.3% 33/91 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.	18.1% 17/94 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.
Injury, poisoning and procedural complications Injection site tenderness	58.2% 53/91 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.	33.0% 31/94 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.
Injury, poisoning and procedural complications Injection site swelling	13.2% 12/91 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.	2.1% 2/94 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.
General disorders Medical attention or medication required	5.5% 5/91 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.	11.7% 11/94 • 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.