Although they occurred only rarely, the risks of iatrogenic and noniatrogenic injuries were significantly increased in the diagnostic period for women with invasive cervical cancer (ICC) compared with those who had a normal cervical smear, according to results of a large, population-based cohort study conducted in Sweden that were published in Cancer Epidemiology, Biomarkers & Prevention.1

Results from previously conducted research have suggested that the time period between first suspicion of cancer and cancer diagnosis may be associated with an increased risk of both iatrogenic and noniatrogenic injuries.2 Nevertheless, this type of association has not been well investigated in the setting of cervical cancer.

This retrospective study evaluated the risks of these types of injuries in a cohort of several million women included in the Swedish Cervical Screening Registry who were older than 18 years during the period between 2001 and 2012.

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Follow-up was initiated in these women starting January 1, 2001, or the date of their eighteenth birthday, whichever occurred later, and continued until a diagnosis of cervical intraepithelial neoplasia grade 3 (CIN3), adenocarcinoma in situ (AIS), or ICC, another type of cancer, a total hysterectomy, emigration from Sweden, death or December 31, 2012.

The diagnostic workup for women with CIN1-2, CIN3/AIS, or ICC was defined as the period between the first smear or punch biopsy until surgery or 2 months after the last smear or biopsy for those who did not undergo surgery. Iatrogenic injuries were defined as being associated with a drug/biological substance or medical procedure/care requiring at least 2 days of hospitalization, whereas noniatrogenic injuries were defined as injuries that were either accidental, intentional, or undetermined that required at least 1 day of hospitalization.

Of the women included in this large cohort, 1,853,510 (95.62%) had a normal cervical smear, whereas 22,435 (1.16%), 20,692 (1.07%), 36,542 (1.89%), and 5189 (0.27%) women were diagnosed with CIN1, CIN2, CIN3/AIS, and ICC, respectively.

In comparison with women with a normal smear and following adjustments for age, calendar period, screening adherence, levels of education and income, and marital status, the incidence rate ratios (IRRs) of iatrogenic injury for those with a diagnosis of CIN1, CIN3/AIS and ICC were 2.04 (95% CI, 1.06-3.93), 3.04 (95% CI, 1.73-5.34), and 8.55 (95% CI, 3.69-19.80). However, no significant increase in IRR was noted for women with CIN2 compared with those who had a normal smear.

With respect to this finding, the study authors noted that “women with invasive cancer have commonly greater vascularity in tumor growth, whereas hemorrhage and hematoma were indeed the most common types of iatrogenic injuries during the diagnostic workup of women with ICC.”

Similar comparisons focused on noniatrogenic injury revealed that only those diagnosed with ICC had a significantly elevated IRR (2.48 [95% CI, 1.30-4.74]) compared with women with normal smear results.

“Women receiving an abnormal result when evaluated for cervical cancer, have been reported to have increased risk of anxiety, distress, sleep disturbance, and poor concentration,” the study authors commented.

Although concluding that these types of injuries were rare in the setting of cervical screening, “the increased rate of iatrogenic and noniatrogenic injuries during the diagnostic workup of women with ICC might indicate burden of medical complications and the severe psychologic distress experienced in relation to receiving a diagnosis of cervical cancer,” commented the study authors.


1. Shen Q, Lu D, Andrae B, et al. Risk of injuries around diagnosis of cervical cancer and its precursor lesions: a nationwide cohort study in Sweden. Cancer Epidemiol Biomarkers Prev. 2020;29(11):2230-2234. doi:10.1158/1055-9965.EPI-20-0673

2. Shen Q, Lu D, Schelin MEC, et al. Injuries before and after diagnosis of cancer: nationwide register based study. BMJ. 2016;354:i4218. doi:10.1136/bmj.i4218