HPV genotype may alter chemoradiotherapy outcome

By Lynda Williams, Senior MedWire Reporter

Human papillomavirus (HPV) genotype predicts whether patients with cervical cancer will benefit from concurrent chemoradiation therapy (CCRT), study findings suggest.

The research, published in the International Journal of Radiation Oncology Biology Physics, indicates that CCRT significantly increased 5-year disease-specific survival in patients with HPV18 (60.9 vs 30.4%) and HPV58 (69.3 vs 48.9%) compared with radiotherapy alone.

After adjusting for age, International Federation of Gynecology and Obstetrics (FIGO) stage, and lymph node status, HPV18 and HPV58 genotypes remained significant predictors for disease-specific survival for CCRT versus radiotherapy alone, with HRs of 0.30 and 0.46, respectively.

But no such improvement over radiotherapy was seen for patients with HPV16 and HPV33, report Ji-Hong Hong (Chang Gung Memorial Hospital, Taoyuan, Taiwan) and co-workers.

"These observations suggest that the risks and benefits of intensive combined modality therapies in advanced cervical cancer should be considered on a case-by-case basis for patients according to HPV genotype," the researchers say.

Sparing HPV16- and HPV33-infected patients from chemotherapy could reduce acute and late toxicity without decreasing efficacy, they explain.

The mechanism behind the impact of HPV genotype on treatment response is "unclear," the team says. While HPV18 infection is associated with aggressive cervical cancer that may benefit from improved local and distal control with CCRT, HPV58 disease is associated with a low risk for nodal metastasis.

"We could not exclude the possibility that the lack of a statistically significant effect of chemotherapy on outcomes within subgroups infected with HPV16 and HPV33 was due to small sample sizes," Hong et al admit.

"However, verifying the results of our study in prospective trials would have a great impact on future treatment of squamous cell carcinoma of the cervix."

The 327 patients with advanced cervical squamous cell carcinoma (FIGO stage III/IVA or IIB plus positive lymph nodes) were treated between 1993 and 2000. The majority (98.8%) were HPV-positive for one or more of 22 genotypes, with HPV16 (38.5%), HPV58 (26.9%), HPV18 (18.0%), and HPV33 (15.6%) the most commonly detected.

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