Cancer cells
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Monitoring even early abnormal cells (lesions) on the cervix rather than removing them straight away increases long term risk of cancer, suggests a recent study from Denmark. While the absolute risk of cervical cancer remains low with surveillance, this approach is associated with a nearly fourfold higher risk of the disease 20 years after an abnormal biopsy.

The study was recently published in the British Medical Journal (BMJ). The lead author is Kathrine Dyhr Lycke of Gødstrup Hospital and Aarhus University, Denmark.

“We believe that it is critical that women who end active surveillance without any excisional treatment undergo more extensive follow-up. They should not return to routine screening,” senior author Anne Hammer Lauridsen tells Inside Precision Medicine. She is head of Research at the department of Obstetrics and Gynecology, Gødstrup hospital, and associate professor at Aarhus University.

Lauridsen further explains that cancer could emerge in areas of the cervix that weren’t being monitored. “The diagnosis relies on where the biopsy is collected,” she says. “Thus, it could be the cancer was located elsewhere on the cervix.” 

Cervical intraepithelial neoplasia (CIN) refers to abnormal changes of the cells that line the cervix. CIN is divided into grades—CIN1, 2, or 3. The higher the number, the more severe and the higher the risk of progression to cancer is. CIN is not cancer, but abnormal cells can develop into cervical cancer if left untreated. CIN2 has been the threshold for large loop excision of the transformation zone (LLETZ). 

But several studies have shown high spontaneous regression rates of CIN2 (50-60% within two years), suggesting a considerable risk of overtreatment if all women with CIN2 are treated with LLETZ. Plus, LLETZ is associated with increased risk of preterm delivery in subsequent pregnancies. So, many countries have implemented active surveillance as an option in younger women with CIN2. Sweden, Norway, Finland, Denmark, the U.K., France, Spain, Portugal, and the U.S. Lauridsen says, all offer this option.  

Her team set out to assess the long term risk of cervical cancer in women having active surveillance for CIN2 compared with immediate treatment.

Active surveillance has been an option for all women of reproductive age in Denmark since 2013 and in some Danish regions since 1995. It involves regular examinations and tests for two years after diagnosis to see if the abnormal cells develop further.

This study included 27,524 women with CIN2 diagnosed in 1998-2020 and aged 18-40 years at diagnosis. Of these, 12,483 (45%) had active surveillance and 15,041 (55%) had immediate treatment with large loop excision of the transformation zone (LLETZ) to remove lesions.

Women were followed from diagnosis until cervical cancer, hysterectomy, emigration, death, or 31 December 2020, whichever came first. 

After taking account of various factors including age, calendar year, and region of residence, the researchers identified 104 cases of cervical cancer—56 (54%) in the active surveillance group and 48 (46%) in the LLETZ group. 

The cumulative risk of cervical cancer was similar across the two groups during the two-year active surveillance period (0.56% in the active surveillance group and 0.37% in the LLETZ group). 

Thereafter, the risk increased in the active surveillance group. After 20 years, the risk was about fourfold higher in the active surveillance group (2.65%), whereas it remained relatively stable in the LLETZ group (0.76%). The increased risk was mainly seen among women aged 30 or older. 

One explanation for the higher long term risk of cervical cancer in women having active surveillance could be that the underlying HPV infection that causes cervical cancer remains dormant in the cells with subsequent risk of reactivation during periods of weakened immune or increasing age, say the researchers.

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