Women co-infected with low-risk and high-risk human papillomavirus (HPV) had a reduced risk for invasive squamous cervical carcinoma and a longer time to progression than did women infected with high-risk human papillomavirus alone, according to a Swedish study published in the Journal of the National Cancer Institute. “We propose that coinfection with low-risk human papillomavirus interferes with the rate of progression to invasive cervical cancer,” wrote Karin Sundström, MD, PhD, of the Karolinska Institutet, Stockholm, and colleagues.
Using data from the Swedish National Cervical Screening Register and the Swedish National Cancer Register, the researchers identified women who had normal baseline smears and later developed cancer in situ (n = 524) or squamous cervical cancer (n = 378), as well as individually matched control subjects who remained free of disease during study follow-up. A total of 4,659 smears were collected and all were tested for HPV.
“The median time from the first smear to diagnosis of the case subject was 6.4 to 7.8 years, yielding a median age at diagnosis of 32 years for cancer in situ and 41 years for squamous cervical cancer,” the authors reported. Infection with high-risk HPV was prevalent in the smears before either a diagnosis of cancer in situ (49%–67%) or squamous cervical cancer (50%–57%).
“The proportion of smears only positive for low-risk HPV was universally low, at 1% to 3%,” the investigators noted. “The proportion of smears positive for both high-risk HPV and low-risk HPV was slightly higher, at 1% to 5%.” Smears coinfected with high-risk and low-risk HPV had between one and six high-risk HPV types, but most had only one low-risk type. The most prevalent low-risk type was HPV42.
The researchers analyzed separately the risk associated with HPV infection in the first and the last smears before a patient’s diagnosis. Women who were coinfected with high-risk HPV and low-risk HPV “had a tendency for a decreased risk for squamous cervical cancer if found in the first smear (relative risk [RR] = 0.4, 95% confidence interval [CI] = 0.10–2.0) and a statistically significantly decreased risk for squamous cervical cancer if found in the last smear (RR = 0.2, 95% CI = 0.04–0.99, P = .049),” the researchers reported. The risks for cancer in situ were the same for women with single and double HPV infection (RR first smear = 0.8, 95% CI = 0.3–1.7; RR last smear = 1.10, 95% CI = 0.4–3.6).
The authors commented: “Antagonistic interaction effects between high-risk and low-risk types of HPV have now been shown in several independent cohorts, using both differing biological material and timing in relation to diagnosis of invasive cancer.” The reasons for the interaction found in this study, however, are not clear, and the authors stated their finding “may merit further replication in other cervical DNA-based studies and investigation of potential underlying mechanisms.” ■
Sundström K, et al: J Natl Cancer Inst. July 9, 2015 (early release online).