Background/Purpose: Cervical neoplasia is increased in women with SLE. HPV types 16 & 18 account for 70% of cervical cancer. Natural HPV cervical infection generates type specific anti HPV antibodies (HPV-Ab) which are usually cross protective and low titer. For this study, HPV-Ab to types 6, 11, 16 and 18 were obtained pre and post vaccine (Phase I trial for Gardasil® in SLE) and analyzed to determine if antibody (Ab) vaccine response (AVR) related to abnormal pap smear/cervical neoplasia (AP/CM) or history (h/o) of preceding HPV infection (HPV-I). AVR in SLE could be suppressed in those with AB/CN, due to inability to clear persistent infection; alternatively, previous exposure could lead to a more vigorous anamnestic response.

Methods: In this trial, approved by the Human Investigation Committee at Wayne State University & the U.S. Food and Drug Administration, 34 women ages 19-50 years (yrs.) with a h/o of mild to moderate SLE by ACR criteria & minimally active or inactive SLE received qHPV vaccine (Gardasil®) at the standard dosing schedule (0, 2 months, 6 months). Patients excluded if they had active disease (SELENA-SLEDAI >2), h/o of severe disease, deep venous thrombosis, on >400 mg/day of hydroxychloroquine, on >15 mg/day of prednisone, or had active infections. Ab titers to HPV 6, 11, 16 &18 and h/o of AB/CN were evaluated pre-vaccine. Ab titers were measured by HPV competitive Luminex Immunoassay. Pearson Chi Square & logistic regression controlling for patient demographics (PD) were used to evaluate pre-vaccine HPV-Ab titers in relation to h/o of AB/CN. Linear regression controlling for PD & t-test were used to evaluate the magnitude of rise of Geometric Mean Titers (GMTs) in relation to h/o of AB/CN or preceding HPV-I.

Results: Women in the study (n=34) were predominantly African-American (79%), mean age 38.1 yrs., mean age at diagnosis of SLE at 28.6 yrs., 32.4% had h/o of smoking, 91% had ≥4 sexual partners, 50% had a h/o of sexually transmitted diseases, & 27.3% used condoms on a regular basis. History of AB/CN occurred in 52.9% {ASCUS (atypical glandular cells of undetermined significance) to CIN 3 (cervical intraepithelial neoplasia grade 3)}. Seven women were negative at baseline for all 4 Ab types in the vaccine; positive HPV Ab titers at baseline were seen in 79 % (n=27) for ≥1 of the HPV types in the vaccine, indicating previous HPV-I in most patients (15=exposed to only one HPV type, 12=exposed to ≥1 of the 4 types). Statistical analysis showed: those with a h/o of AP/CN were likely to have a positive HPV Ab result pre-vaccine to ≥ 1 of the 4 types contained in the vaccine, p=0.035. However, there was no difference in the magnitude of rise of HPV-Ab GMTs between those with a history of AB/CN vs. those that had no h/o of AB/CN or between those with preceding HPV-I vs. those who were Ab negative at baseline.

Conclusion: Our study shows that in women with SLE, the presence of HPV-Ab for 6, 11, 16, and 18 prior to receiving q HPV vaccine clearly correlates with h/o of AB/CN. However, neither AB/CN nor preceding HPV-I had an impact on humoral response to vaccination, showing no anamnestic response to previous natural infection. This supports not checking HPV antibody status before vaccinating women with SLE.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/does-a-history-of-abnormal-pap-smear-or-preceeding-hpv-infection-affect-humoral-immune-response-to-quadrivalent-human-papilloma-virus-qhpv-vaccine-in-women-with-systemic-lupus-erythematosus-sle/