Long-term Immunogenicity of a HPV Vaccine in SLE

Long-term Immunogenicity of a Quadrivalent Human Papillomavirus (HPV) Vaccine in Patients With Systemic Lupus Erythematosus: a Case-control Study

To study the 5-year immunogenicity against a quadrivalent HPV vaccine in patients with SLE and healthy controls.

Study Overview

• Status: Completed
• Conditions: Systemic Lupus Erythematosus
• Intervention / Treatment: Biological: Vaccination

Detailed Description

Most cases of human papilloma virus (HPV) infection are asymptomatic, transient and resolve without treatment. However, in some individuals, especially those patients who are immunocompromised because of various underlying diseases and those who are receiving long-term immunosuppressive agents, HPV infection is persistent and may result in genital warts, cervical smear abnormalities, cervical intraepithelial neoplasia (CIN) and rarely cervical cancer.

High-risk HPV serotypes are those which are oncogenic and associated with invasive cancers of the cervix and vulva. Examples are the HPV 16 and HPV 18. HPV 16 accounts for almost half of all cervical cancers whereas HPV 18 infection is present in 10-12% of all cervical cancers.

Systemic lupus erythematosus (SLE) patients are at risk of persistent HPV infection. This is because of the immune aberration related to the disease itself and the immunosuppressive state induced by various treatments. One study of 85 SLE patients revealed a 16.5% prevalence of abnormal Pap smears and 12% prevalence of cervical squamous intraepithelial neoplasia (CIN) on routine screening, which was significantly higher than those figures reported in age-matched healthy women (corresponding figures for abnormal Pap smear and CIN were 5.7% and 2%, respectively). Thus, prevention of HPV infection is important in patients with SLE in order to reduce the incidence of CIN lesions and hence invasive cervical cancers in the long run.

The investigators have conducted a case-control study on the safety and immunogenicity of the quadrivalent HPV vaccine, GARDASIL, in 2010. Fifty female SLE patients and 50 age-matched healthy controls were studied. At month 12 after vaccination, the sero-conversion rates of anti-HPV serotypes 6, 11, 16 and 18 in patients and controls were 82%, 89%, 95%, 76% and 98%, 98%, 98%, 80%, respectively. Injection site reaction was the commonest adverse event (AE) (5%), and the incidence of AEs was comparable between patients with SLE and controls.

The investigators plan to study the long-term immunogenicity (durability of the immune response) of the HPV vaccine in the same cohort of patients and controls followed for 5 years. In particular, in patients with SLE, the investigators would like to evaluate the effect of disease flares and ongoing immunosuppressive treatment on the immune response to the HPV serotypes 5 years after vaccination.

• Study Type: Observational
• Enrollment (Actual): 84

Contacts and Locations

Study Locations

• China
  • Hong Kong, China, 000
    • Department of Medicine, Tuen Mun Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 33 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

SLE patients

1. Female patients aged 18-35 years
2. Fulfilling the American College of Rheumatology (ACR) criteria for the classification of SLE
3. Having participated in the investigators' original HPV study in 2010
4. Able to give written informed consent

Controls

1. Women aged 18-35 years, matched those of SLE patients recruited
2. No known chronic medical diseases
3. Having participated in our HPV study in 2010

Description

Inclusion Criteria:

SLE patients

1. Female patients aged 18-35 years
2. Fulfilling the American College of Rheumatology (ACR) criteria for the classification of SLE
3. Having participated in the investigators' original HPV study in 2010
4. Able to give written informed consent

Controls

1. Women aged 18-35 years, matched those of SLE patients recruited
2. No known chronic medical diseases
3. Having participated in our HPV study in 2010

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
SLE patients; SLE patients who received HPV vaccination	Biological: Vaccination; A quadrivalent HPV vaccine
Control subjects; Healthy subjects who received HPV vaccination	Biological: Vaccination; A quadrivalent HPV vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neutralizing antibodies to HPV serotypes 6,11,16 and 18	proportion of subjects in each arm who remains sero-converted for each HPV serotype at 5 years after vaccination	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neutralizing antibodies to HPV serotypes 6,11,16 and 18	the change in anti-HPV titers at 5 years as compared to 12 months post-vaccination	5 years

Collaborators and Investigators

• Sponsor: Tuen Mun Hospital
• Investigators: Principal Investigator: CC Mok, MD, Tuen Mun Hospital

Publications and helpful links

General Publications

• Mok CC, Ho LY, To CH. Long-term immunogenicity of a quadrivalent human papillomavirus vaccine in systemic lupus erythematosus. Vaccine. 2018 May 31;36(23):3301-3307. doi: 10.1016/j.vaccine.2018.04.056. Epub 2018 Apr 24.

Study record dates

Study Major Dates

• Study Start: July 1, 2015
• Primary Completion (Actual): May 1, 2016
• Study Completion (Actual): October 1, 2016

Study Registration Dates

• First Submitted: June 17, 2015
• First Submitted That Met QC Criteria: June 19, 2015
• First Posted (Estimate): June 22, 2015

Study Record Updates

• Last Update Posted (Estimate): October 19, 2016
• Last Update Submitted That Met QC Criteria: October 17, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: lupus
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Connective Tissue Diseases; Lupus Erythematosus, Systemic
• Other Study ID Numbers: NTWC/CREC/15035