The rate of cervical human papillomavirus infection among women with systemic lupus erythematosus increased from 12% to 25% after 3 years, judging from results from a novel study presented at the annual European Congress of Rheumatology.
Moreover, patients were twice as likely to acquire high-risk HPV infection than low-risk HPV infection.
“Information about the natural history of HPV infection in SLE is lacking,” lead investigator Dr. Lai-Shan Tam said in an interview. “Whether immunosuppression related to SLE itself and/or the use of immunosuppressants would result in an increased incidence and risk of persistent HPV infection has never been studied.”
Dr. Tam and her associates evaluated 144 women with SLE at 6-month intervals for up to 3 years. During each visit, a Pap test, a test for HPV DNA, and a clinical assessment were performed in an effort to ascertain the incidence, clearance, and persistence of HPV infection. The mean age of the patients was 41 years, and mean disease duration was 8.6 years. The total duration of follow-up was 4,006 patient-months.
The cumulative prevalence of HPV infection increased from 12% at baseline to 25% after 3 years, and 19% of patients experienced a total of 69 incident infections, reported Dr. Tam of the department of medicine and therapeutics at the Chinese University of Hong Kong. The researchers also observed a twofold increase in the overall incidence of high-risk HPV infection, compared with the low-risk type (11.6 per 1,000 patient-months vs. 5.4 per 1,000 patient-months, respectively).
“Other studies on healthy women found that 19%-38% of those [who] tested positive for HPV harbored multiple HPV types,” Dr. Tam said. “Such prevalence is much lower than that observed in our lupus cohort (65%).”
She went on to note that other studies on the natural history of cervical HPV infection in healthy subjects showed that most incident infections were transient, lasting less than 6 months. In contrast, the rate of persistent infection in this cohort of SLE patients appeared increased (49%).
The cumulative prevalence of multiple HPV infection also increased significantly (10/145 [6.9%] at baseline to 25/145 [17.2%] after 3 years, P = .007). The most common newly acquired high risk viral type was HPV-16 and-52 (1.7 per 1,000 patient-months), followed by HPV-18, −56 and −58 (1.2 per 1,000 patient-months).
In all, 20 out of 145 (13.8%) patients experienced at least one episode of persistent infection. The majority (overall infection: 34/69 [77.3%]; high-risk HPV: 23/30 [76.7%]; low-risk: 11/14 [8.6%]) of the incident HPV infections persisted for at least 6 months. Overall, 11/37 (29.7%) patients were able to clear all HPV infections.
Regarding the type-specific infections, the cohort participants cleared 33/38 (86.8%) of the pre-existing infections and 14/44 (31.8%) of all the incident infections.
The researchers also noticed that patients with high inflammatory burden as reflected by a SLICC/ACR (Systemic Lupus Erythematosus International Collaborating Clinics/American College of Rheumatology) Damage Index score of 1 or greater were at higher risk of acquiring HPV infection, after adjustment for the known risk factors as well as the use of immunosuppressants.
“In other reports of healthy young females, infection with high-risk types and multiple infections were risk factors for persistent infection,” Dr. Tam said. “In contrast, lupus patients with any HPV infections at baseline are at risk of having persistent infection regardless of risk type.” Independent risk factors associated with persistent HPV infection in SLE included preexisting HPV infection (P = .04) and multiple HPV infection during first incident infection (P = .02).
Independent risk factors associated with incident HPV infection included younger age at first sexual intercourse (P = .025; odds ratio, 0.868; 95% confidence interval, 0.766-0.983) and baseline SLICC =1 (P = .038; OR, 2.619; 95% CI, 1.054-6.508).
Independent risk factors associated with persistent HPV infection included pre-existing HPV infection at baseline (P < .001; OR, 89.47; 95% CI, 9.25-865.28) and multiple HPV infection during first incident infection (P < .001; OR, 188.11; 95% CI, 19.04-1858.42).
She acknowledged certain limitations of the study, including the lack of a healthy control group and the fact that that most of the patients in the study did not belong to the age group at highest risk for HPV.
The study was commissioned by the Food and Health Bureau of the Hong Kong SAR government, and was funded by the Research Fund for the Control of Infectious Diseases. This study was also supported by a Chinese University of Hong Kong research grant.
The cumulative prevalence of HPV infection increased from 12% at baseline to 25% after 3 years. DR. TAM