Why “Autoimmune ConnectionS” plural?
Ongoing research is revealing new connections in autoimmunity, bolstering the more speculative links, and disproving others.
For example: a connection between lupus and an increased risk of cervical cancer has been suggested for years – it has now been confirmed. This is an important issue if you have SLE and possibly other autoimmune diseases.
The confirmation came at the recent European League Against Rheumatism (EULAR) annual meeting in London. A new study from Sweden found a doubled rate of cervical dysplasia or neoplasms – premalignant abnormal cell growth – among women with SLE in general and a greater risk among women treated with immunosuppressant drugs.
“We know that the therapies we use to treat lupus, particularly complicated lupus, are therapies that compromise normal immune function. They are also therapies we use in the organ transplant setting, where we know there are a number of malignancies that occur more often than expected, in particular premalignancies and frank malignancies of the female cervix,” explained study co-author Johan Askling, MD, PhD, a professor and senior physician at the Karolinska Institute in Stockholm at a EULAR press briefing.
“Is this driven by premalignant cell changes or frank malignancies or was the risk driven by the disease or the other things, such as the therapies we use? The aim of our study was to settle the controversy,” he commented.
Dr. Askling and colleagues examined medical data for 4,550 SLE patients in Sweden’s National Patient Register, separating them into two groups: 1,981 treated with immunosuppressants, such as azathioprine (Imuran), and 1,783 treated with anti-malarials, like hydrochloroquine. Then they compared the SLE patients to 28,113 age-matched women in the general population.
When the researchers looked at cervical cancer screening records between 2006 and 2012 from the Cervical Screening Registry and the Swedish Cancer Registry, they found the rate of cervical dysplasia or invasive cancer among women with SLE was 2.12 greater than for women in the general population.
Among lupus patients given antimalarials, the rate was 1.52 but it was 2.72 for patients on immunosuppressants (with or without antimalarials). The risk held up even when factoring in age and earlier cervical screening in the previous five years.
The study, published in abstract form in the June Annals of the Rheumatic Diseases, concludes that “SLE patients treated with immunosuppressants are at risk of cervical neoplasia and should be adequately monitored, regardless of whether the risk increase is due to disease severity or treatment.”1
The SLE-Cervical Cancer Connection
An elevated rate of cervical dysplasia among lupus patients has been reported for a number of years2,3 and associated with exposure to immunosuppressive drugs, including azathioprine.
“An altered clearance of cancer related viral agents in SLE (due to the disease and/or immunosuppression) may contribute to this risk and may also drive the risk for other cancers (such as vulvovaginal and hepatic carcinomas) in SLE,” the authors of a 2012 Canadian study note. 4 Immunosuppressive drugs may also be associated with increased susceptibility to human papilloma virus (HPV), which causes most cervical cancers and has been detected more frequently in women with SLE.4
The current Swedish analysis is significant because it’s large – almost 33,000 people – and analyzes results of cervical screening among women with and without SLE as well as SLE patients on anti-malarials or immunosuppressants, comparing then with women in the general population. So this analysis is able to quantify the risk.
However, we should stress that the Swedish data come from an abstract reported at a scientific meeting, are not final, and haven’t yet been peer-reviewed. Plus, population studies such as this can’t prove cause-and-effect -- just an “association” with increased risk.
Dr. Askling, who has been studying cardiovascular disease and cancer risk in rheumatoid arthritis and other autoimmune diseases, also notes that both RA and CVD are, in part, driven by inflammation. Studies of cancer in autoimmune diseases also show that higher disease activity may also increase risk.
Should SLE Patients be Alarmed?
Fortunately, screening tests using new liquid based cell analysis cytology) which can detect DNA from HPV are very sensitive. And, if cervical dysplasia or intraepithelial neoplasia (CIN) are found the condition can be treated with freezing or electrocauterization before it can progress to cancer.
Considering the potentially increased risk for women with SLE, is more frequent cervical screening needed? That’s something to ask your gynecologist.
Depending on a woman’s health history, 2016 guidelines from the American College of Obstetricians and Gynecologists (ACOG), the American Cancer Society (ACS), and other groups advise cervical cytology screening every three years for sexually active women ages 21–29 at average risk;5 the ACS recommends both cervical screening and HPV testing.6 Women ages 30–65 years are urged to have both tests every 5 years with high-risk HPV strains. Since cervical cancer is less common in older women, after age 65 screening can be stopped if consecutive Pap and HPV tests have been negative.6
Women with SLE are screened at about the same rate as women in the general population (around 89% ), Dr. Askling told interviewers at the EULAR meeting.7 “And we should keep encouraging women with lupus to be screened because it has “demonstrated true value. And here’s a group with an increased risk potentially more driven by the earlier stages of cervical cancer than by invasive cancer.”7
Also important: the Lupus Foundation notes that women with SLE also seem to be more vulnerable to the effects of certain cancer-linked viruses than the general population.8 A case in point: human papilloma virus. So younger lupus patients may also want to ask their doctors about the HPV vaccine.
New liquid-based cytology tests can detect DNA of HPV in cervical cells even before dysplasia or CIN occur. That’s another reason to be regularly screened. As we advised in “The Autoimmune Connection,” find a gynecologist familiar with ADs to help guide you in deciding how frequently to be screened.
Since immunosuppressant drugs like azathioprine appear to play a role in this increased risk, you may also want to discuss alternative treatments with your rheumatologist. Ultimately, the choice depends on the medication that best controls your SLE.
1 H. Wadström, E.V. Arkema, C. Sjöwall , J. Askling , et al., Rate of Cervical Neoplasia in Systemic Lupus Erythematosus: A Nationwide Cohort Study. EULAR Abstract: OP0189. Annals of the Rheumatic Diseases. June 2016. DOI: 10.1136/annrheumdis-2016-eular.2142.
2 Tessier-Cloutier B , Clarke AE , Ramsey-Goldman R, et al., Systemic lupus erythematosus and malignancies: a review article. Rheum Dis Clin North Am. 2014 Aug;40(3):497506, viii. doi: 10.1016/j.rdc.2014.04.005. Epub 2014 Jun 3.
3 Gayed M , Bernatsky S, Ramsey-Goldman R, Clarke A, Gordon C. Lupus and cancer. Lupus. 2009 May;18(6):47985. doi: 10.1177/0961203309102556.
4 Bernatsky S , Kale M, Ramsey-Goldman R, Gordon C, Clarke AE. Systemic lupus and malignancies. Curr Opin Rheumatol. 2012 Mar;24(2):17781. doi: 10.1097/BOR.0b013e32834ff258.
5 ACOG Practice Bulletin No. 157 Summary: Cervical Cancer Screening and Prevention. Obstetrics & Gynecology, January 2016; 127(1):185-187. doi: 10.1097/AOG.0000000000001256.
6 Sawaya GF, MD; Kulasingam S, Denberg TD, et. al., Cervical Cancer Screening in Average-Risk Women: Best Practice, Advice From the Clinical Guidelines Committee of the American College of Physicians. Ann Intern Med. 2015;162:851-859. doi:10.7326/M14-2426.
7 Johan Askling profile page, Karolinska Intitutet. http://ki.se/en/people/johask. Accessed July 1, 2016
8 The Lupus Foundation, Cancer and Lupus, 15 Questions. www.lupus.org/resources/15-questions-with-Sasha-Bernatsky-cancer-and lupus/ Accessed July 1, 2016.