Early Posttherapy Clearance of HPV May Be Associated with Improved Survival for Cervical Cancer

Researchers suggested that this 6-week window may represent a critical time point at which decisions could be made regarding treatment escalation for this patient population.

A study published in Cancer found that early posttherapy clearance of human papillomavirus (HPV) is associated with improved survival for patients with cervical cancer.

Researchers suggested that, given these results, this 6-week window may represent a critical time point at which decisions could be made regarding treatment escalation for this patient population.

“Notably, other biomarkers such as circulating HPV DNA have been evaluated in this setting, with a study published earlier this year demonstrating that elevated HPV DNA levels 3 months after treatment portend a worse prognosis,” the authors wrote. “However, our study identifies a prognostic biomarker at an earlier time point, 6 weeks, which would allow for earlier incorporation of consolidative therapies.”

In this study, researchers evaluated patients who underwent pretreatment testing indicating a high-risk HPV infection and posttreatment testing with a messenger RNA (mRNA)–based genital swab following chemoradiation. Posttherapy responses were then stratified based on HPV mRNA detection into an early clearance group (no mRNA) and a persistent expression group (detectable mRNA) on the basis of an evaluation at a median of 6 weeks after therapy.

In total, 72 of 97 eligible patients (74.2%) were classified as early clearance. The mean follow-up time was 25 months (range, 4-56 months), and 2-year pelvic control (76.9% vs 50.2%; P = .01) and overall survival (OS; 80.9% vs 52.2%; P < .01) were found to be superior among patients with early clearance.

In multivariable analysis, early clearance predicted for improved survival (HR for mortality, 0.46; 95% CI, 0.21-0.96; P = .047), as did a complete response (CR) on posttherapy PET (HR for less than a CR on PET, 6.17; 95% CI, 2.58-14.72; P < .01). Moreover, in a subset analysis of patients with a posttherapy PET CR, HPV clearance maintained prognostic significance (2-year OS, 95.6% with early clearance vs 66.7% with persistent expression; P = .04), while patients with persistent expression without a PET CR had the worst survival (35.9%; P < .01 for trend).

“Therefore, pending prospective validation, evaluation of HPV expression at this time point may aid in the risk stratification of patients and in the decision for consolidative therapies,” the authors wrote.

Notably, these findings are only representative of a single institution’s experience, and the genital swab technique that was used to obtain HPV data may be subject to a sampling error. Additionally, the authors indicated that though this study is the first to evaluate both HPV clearance and posttreatment PET, the numbers within each subgroup were relatively small. Further, though significant differences were observed in outcomes by subgroup, the overall small numbers do limit the generalizability of the study results.

“Even with these questions and limitations in mind, our study is the first to show that PE of HPV within 6 weeks of definitive treatment with modern CRT portends a poor prognosis independently of other known prognostic markers such as posttherapy FDG-PET findings,” the authors concluded. “However, these findings and other novel findings such as the decreased clearance seen in HPV-18 patients warrant further investigation and validation before implementation in the clinic.”


Srivastava AJ, Contreras JA, Davis M, Markovina ST, Schwarz JK, Grigsby PW. Early Posttherapy Clearance of Human Papillomavirus and Treatment Response in Cervical Carcinoma. Cancer. doi: 10.1002/cncr.33040.