NEW YORK (Reuters Health) – The identification of differing patterns of oncogenic mutations in squamous cell carcinoma and adenocarcinoma of the cervix may lead to more targeted treatments, a Massachusetts-based team reports.

“While current management strategies do not take histological classification of tumors into account,” they write in Cancer online August 23, “our study suggests that efforts to identify and target distinct molecular subpopulations within cervical cancer may provide an important opportunity to improve outcomes in women with both early and late-stage disease.

Dr. Alexi A. Wright, at the Dana-Farber Cancer Institute in Boston, and colleagues note that cervical adenocarcinoma has a worse prognosis than squamous cell carcinoma, but variations in molecular profiles between the two histologic subtypes that might explain this difference have not been explored.

The team therefore performed a molecular analysis of 40 cervical adenocarcinomas and 40 cervical squamous cell carcinomas using a high-throughput genotyping platform, looking for 1250 known mutations in 139 cancer genes.

They found such mutations in 48 of the 80 tumors (60%). The genes with the highest mutation rates were PIK3CA (31.3%), KRAS (8.8%) and EGFR (3.8%).

PIK3CA mutations occurred at a similar rate in adenocarcinomas (25.0%) and squamous cell carcinomas (37.5%; p=0.33). On the other hand KRAS mutations were detected only in adenocarcinomas (17.5% vs. 0%; p=0.01), while EGFR mutations occurred only in squamous cell carcinomas (0.0% vs. 7.5%; p=0.24), according to the report.

Median overall survival was shorter in patients with PIK3CA mutations (67.1 months) than in those without the mutations (90.3 months), which translated to a hazard ratio of 9.1 (p<0.0001) after adjustment for tumor stage and lymph node involvement.  Conversely, KRAS mutations were not associated with survival (HR 0.31; p=0.26), Dr. Wright and colleagues report.

“Our findings,” they conclude, “suggest that cervical cancers harbor high rates of potentially targetable oncogenic mutations.”

They point out that therapeutics targeting KRAS mutations is an active area of research, with MEK inhibitors showing promise.

Furthermore, they add, “The high prevalence of PI3KCA mutations suggests that PI3K targeted agents should be explored in cervical cancer, particularly in light of recent findings from a phase I trial population which demonstrated that 40% (2/5) of cervical cancer patients with PIK3CA mutations had a clinical response to PI3K/AKT/mTOR inhibitors.”