Women with SLE are at
increased risk for HPV-related cervical disease. The qHPV vaccine immunizes and
is protective against HPV types that cause the majority of cervical cancer
(types 16 &18) and genital warts (types 6 &11).This study evaluated the
safety and immunogenicity of qHPV vaccine in SLE.

Methods:

In this
trial, 34 women ages 19-50 years
(yrs.) with a history of mild to moderate SLE by ACR criteria & minimally
active or inactive SLE received qHPV vaccine at the standard dosing schedule
(0, 2 months, 6 months). This study was approved by the Human Investigation
Committee at Wayne State University & the U.S. Food and Drug
Administration. Patients were excluded if they had active disease
(SELENA-SLEDAI >2), history of severe disease, deep venous thrombosis, on
>400 mg/day of hydroxychloroquine, on >15 mg/day of prednisone, or
had active infections.  Patients were monitored for adverse events (AE), SLE
flare, generation of thrombogenic antibodies and thrombosis.  Antibody (Ab) levels
to HPV 6,11,16 &18 were evaluated pre-vaccine administration and one month
after the 3^rd vaccine shot. Ab levels were measured by HPV
competitive Luminex Immunoassay. Analysis of rise in Geometric Mean
Titers (GMTs) was performed using paired t-tests and of seropositivity status
(y/n) using McNemar’s test. 

Results:

The women
in the study: African-American (79%), mean age 38.1 yrs., mean age at diagnosis
of SLE at 28.6 yrs., 32.4% had a history of smoking, 91% had 4 or more sexual
partners, 50% had a history of sexually transmitted diseases, and only 27.3%
used condoms on a regular basis. History of abnormal pap smears occurred
in 52.9% {range: ASCUS (atypical glandular cells of undetermined significance)
to CIN 3 (cervical intraepithelial neoplasia grade 3)}. Vaccine site reactions
(VSRs) occurred in 59%, all mild, most common reaction being pain (VSRs in
normal women=83.9% for Gardasil® vs. 75.4% for controls). For the non-vaccine
site AEs (nvAE), 97% experienced at least one nvAE;
there were 487 nvAEs reported from 33 patients and 90% of these were mild.
There were 9 serious AEs, none related to vaccine or SLE and all resolved. The
most common nvAEs reported were musculoskeletal (n=106) followed by nervous
system (n=98, mostly headaches), gastrointestinal (n=49), general disorders
(n=45) and dermatologic (n=45). None of the nvAEs were related to vaccine or
SLE. No patient experienced any flare of SLE, thrombosis, or generation of
thrombogenic antibodies.

Positive HPV
Ab titers were seen in 21-53% of the women at baseline for all HPV types (52.9%
for HPV 6, 20.6% for HPV 11, 44.1% for HPV 16 & 20.6% for HPV 18), indicating
previous exposure to the HPV types in the vaccine. Highly immunogenic responses
were seen in all patients. There was a statistically significant rise in mean (GMTs)
post vaccine series completion for both HPV naive and HPV exposed women for all 4 HPV
types, with a
seroconversion rate of 100% in HPV naïve women. 

Conclusion:

Preliminary
data from our study shows that qHPV vaccine is generally safe, well tolerated,
and highly immunogenic in women with SLE. These results suggest that the
qHPV vaccine may be of benefit in women with SLE who are at increased risk for
HPV-related cervical disease.