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

<b>Background</b>: 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. <b>Methods</b>: 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. <b>Results</b>: We verified increased carcinoma risk in individuals with early sexual intercourse (OR: 1.41 [95% CI 1.09 to 1.83], <i>p =</i> 0.0083), non-monogamous sexual partners (OR: 3.13 [95% CI 2.15 to 4.57], <i>p</i> < 0.0001), three or more live births (OR: 1.44 [95% CI 1.12 to 1.84], <i>p =</i> 0.0040), and high PRS (polygenic risk score) (top 25% of PRS, OR: 1.58 [95% CI 1.15 to 2.16], <i>p =</i> 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], <i>p</i> < 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], <i>p</i> < 0.0001) compared to individuals with favorable behavior and low genetic risk. <b>Conclusions</b>: 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.