Increased Risk of Second Squamous Cell Carcinomas Following Cervical Cancer: A Nationwide Danish Case–Control Study

TL;DR

Cervical cancer survivors in Denmark have a higher risk of developing second squamous cell carcinomas, especially lung cancer, compared to cancer-free women.

Contribution

This nationwide study identifies an increased risk of second squamous cell carcinomas in cervical cancer survivors, emphasizing the need for targeted surveillance.

Findings

Cervical cancer survivors had a lower overall risk of second primary cancers but a higher risk of lung cancer.

Survivors of squamous cell carcinoma of the cervix had significantly increased risks of second squamous cell carcinomas at HPV-related and non-HPV sites.

Lung squamous cell carcinoma risk was notably elevated among cervical cancer survivors.

Abstract

This nationwide case–control study investigated the risk of second primary cancers among cervical cancer (CC) survivors compared to cancer‐free women.

Women aged ≥ 18 diagnosed with CC from 1987 to 2012 were identified via the Danish Cancer Registry (DCR) and matched 1:5 by age and residence to cancer‐free controls. A subpopulation with histologically confirmed squamous cell carcinoma of the cervix (SCC‐C) was defined using the Danish Pathology Register. Adjusted sub‐hazard ratios (aSHR) for subsequent primary cancers were estimated.

The study included 10,728 CC cases and 53,597 matched controls, including 7910 SCC‐C cases and 39,358 controls. Over a median follow‐up of 14.2 years, CC survivors had a modest but statistically significant reduction in the overall risk of second primary cancers (aSHR: 0.87; 95% CI, 0.81–0.93), including lower risks of colorectal cancer (aSHR: 0.77; 95% CI, 0.63–0.93), breast cancer (aSHR: 0.76; 95% CI, 0.67–0.87), and malignant melanoma (aSHR: 0.59; 95% CI, 0.42–0.84). In contrast, the risk of lung cancer was increased (aSHR: 1.33; 95% CI, 1.15–1.54). Among SCC‐C survivors, the risk of second SCC was increased at both HPV‐related sites (aSHR: 1.78; 95% CI, 1.18–2.68) and non‐HPV sites (aSHR: 2.59; 95% CI, 1.92–3.47), primarily due to a marked increased risk of lung SCC (aSHR: 2.88; 95% CI, 1.97–4.20).

Although the overall risk of second primary cancers was lower among CC survivors compared to controls, the increased incidence of second SCCs, particularly lung SCC, highlights the need for targeted long‐term surveillance strategies.

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