Obesity Impedes Detection of Cervical Precancer, Increasing Cancer Risk

Megan Clarke, PhD

Women with a body mass ≥30 kg/m² had a greater 5-year risk for cervical cancer than lighter women, possibly due to underdiagnosis of cervical precancer.

Compared with normal weight/underweight women (BMI <25 kg/m²) or overweight (BMI 25 to <30 kg/m²) women, obese women (BMI ≥30 kg/m²) had the lowest 5-year risk for precancer (0.51%; 95% CI, 0.48%-0.54%; P trend <.001), but the highest 5-year risk for cancer (0.083%; 95% CI, 0.072%-0.096%). Five-year risk for precancer was 0.73% (95% CI, 0.70%-0.76%) and 5-year risk for cancer was 0.056% (95% CI, 0.048%-0.066%) in normal/underweight women (P trend <.001).

“These findings were consistent irrespective of age, race/ethnicity, HPV status, and histology. Any risk factor associated with increased cervical cancer risk would also be expected to increase precancer risk, and likewise, a decreased precancer risk should lead to a corresponding decreased risk of cancer,” first author Megan Clarke, PhD, Division of Cancer Epidemiology & Genetics, National Cancer Institute, and colleagues wrote.

“Thus, the apparent paradoxical association of excess BMI with decreased risk of precancer, but increased risk of cancer, is likely related to underdiagnosis of cervical precancer in overweight and obese patients who were screened for cervical cancer,” added Clarke et al.

Clarke et al conducted a retrospective cohort study of 1,659,496 women who had undergone screening by conventional cytology and/or liquid-based cytology combined with HPV testing at Kaiser Permanente Northern California (KPNC) from January 2003 to December 2015. KPNC, a large, integrated healthcare system, implemented an intensive program with triennial cervical cytology and HPV cotesting among women aged ≥30 years in 2003. A total of 944,227 women were included in this analysis.

Most women (70.8%) in the study were aged 30 to 49 years, and 31.3% were classified as obese. A majority (39.8%) were white but investigators found that black and Hispanic women were more likely to be overweight or obese while Asian women were less likely to be overweight or obese.

On average, women had 4.4 years of follow-up and 2.9 screening tests. Approximately 6.3% of women were HPV positive, and investigators observed a trend toward decreasing HPV prevalence with increasing BMI (P trend <.001), regardless of age.

Overall, 4489 women (0.48%) developed cervical intraepithelial neoplasia grade 3 (CIN3) or adenocarcinoma in situ (AIS). Of these, 1998 patients were classified as normal/underweight (44.4%), 1339 as overweight (29.8%), and 1152 as obese (25.6%).

A total of 490 women (0.05%) were diagnosed with cancer. Of these, 149 (30.4%) were classified as normal/underweight, 154 (31.4%) as overweight, and 187 (38.2%) as obese.

The risk for CIN3/AIS declined with increasing BMI (P trend <.001). This association was consistent for both prevalent CIN3/AIS (overweight: OR, 0.86; 95% CI, 0.78-0.94; obese: OR, 0.72; 95% CI, 0.66-0.79) and incident CIN3/AIS (overweight: HR, 0.80; 95% CI, 0.70-0.90; obese: HR, 0.66; 95% CI, 0.58-0.76).

Obese women had the lowest 5-year cumulative risk for CIN3/AIS (0.51%; 95% CI, 0.48%-0.54%), followed by overweight women (0.61%; 95% CI, 0.58%-0.64%). Normal/underweight women had the highest 5-year cumulative risk (0.73%; 95% CI, 0.70%-0.76%).

Investigators found that the trend held even after adjusting for age and race/ethnicity, and after excluding underweight women. The findings were also consistent for grade 2 CIN risk.

The 5-year cumulative risk for cancer was higher with increasing BMI (P trend <.001). As with CIN3/AIS, the association was consistent for both prevalent disease (overweight: OR, 1.22; 95% CI, 0.94-1.57; obese: OR, 1.48; 95% CI, 1.16-1.89) and incident disease (overweight: HR, 1.64; 95% CI, 0.96-2.78; obese: HR, 1.77; 95% CI, 1.06-2.96).

Obese women had the highest 5-year cumulative risk for cancer (0.083%; 95% CI, 0.072%-0.096%), followed by overweight (0.071%; 95% CI, 0.060%-0.082%) and normal/underweight women (0.056%; 95% CI, 0.046%-0.064%). Again, the trends were similar after adjusting for age and race/ethnicity, and excluding underweight women.

“To our knowledge, ours is the first study to evaluate the influence of BMI on the efficacy of cervical cancer screening in a large, routinely screened population of women,” investigators wrote. “This study has implications regardless of whether the screening program uses cytology, HPV testing, or both. By evaluating the joint distribution of baseline cotest results by worst diagnosis and BMI, we found that reduced sensitivity of both HPV and cytology testing may contribute to underdiagnosis of precancer in overweight and obese women.”

Clarke MA, Fetterman B, Cheung LC, et al. Epidemiologic evidence that excess body weight increases risk of cervical cancer by decreased detection of precancer [published online January 22, 2018]. J Clin Oncol. doi: 10.1200/jco.2017.75.3442.