# Risk of Cervical Carcinoma After Unfavorable Behavior and High Genetic Risk in the UK Biobank: A Prospective Nested Case–Control Study

## TL;DR

This study shows that risky sexual behavior and high genetic risk significantly increase the chance of cervical cancer, especially when both factors are present.

## Contribution

The study introduces a behavior score and demonstrates a combined effect of behavior and genetic risk on cervical carcinoma.

## Key findings

- Unfavorable sexual behavior increases cervical cancer risk by up to 151%.
- High genetic risk combined with risky behavior leads to a 5.5-fold increased cancer risk.
- Early sexual activity and multiple births are significant risk factors.

## Abstract

Background: Previous studies have established a general understanding of the association between risky sexual behavior, genetic risk, and cervical carcinoma. However, these studies were conducted several years ago and lack systematic analysis using high-quality and population-based data. Methods: We conducted a prospective nested case–control study to identify risky behaviors and developed a behavior score. Combining the behavior score and genetic risk, we evaluated the effect of sexual and reproductive behavior and PRS on cervical carcinoma through the developed conditional logistic regression models. Results: We verified increased carcinoma risk in individuals with early sexual intercourse (OR: 1.41 [95% CI 1.09 to 1.83], p = 0.0083), non-monogamous sexual partners (OR: 3.13 [95% CI 2.15 to 4.57], p < 0.0001), three or more live births (OR: 1.44 [95% CI 1.12 to 1.84], p = 0.0040), and high PRS (polygenic risk score) (top 25% of PRS, OR: 1.58 [95% CI 1.15 to 2.16], p = 0.0044). The unfavorable sexual and reproductive behavior score we developed was linked to a 151% increased risk (OR: 2.51 [95% CI 1.79 to 3.52], p < 0.0001) after adjusting for PRS. Women with both unfavorable behavior and high genetic risk had a 5.5-fold increased cervical carcinoma risk (OR: 5.45 [95% CI 2.72 to 10.95], p < 0.0001) compared to individuals with favorable behavior and low genetic risk. Conclusions: Unfavorable sexual and reproductive behavior increases the risk of cervical carcinoma, especially in those with a high genetic risk. These findings encourage us to adhere to a healthy sexual and reproductive pattern.