Researchers Continue to Develop Less Toxic Treatments for HPV+ Oropharyngeal Cancers

While the prognosis remains good for individuals with HPV-positive oropharyngeal cancers, the incidence of these cancers continues to rise, and researchers are currently seeking less intense treatment options that are equally effective but not as toxic for patients.

Oncogenic HPV infection is now a recognized etiology in approximately half of oropharyngeal squamous cell cancers. HPV-positive cancers typically have better outcomes and a lower likelihood of second primary cancers than their HPV-negative counterparts.

On the other hand, the incidence of oropharyngeal cancers is growing — now surpassing cervical cancer — and the increase is expected to continue over the next 30 years, particularly for men currently aged 40 years and younger.

“This is a major public health concern of our time,” said Missak Haigentz Jr, presenting an update on treatments for head and neck cancers last week at the 33rd Annual Chemotherapy Foundation Symposium, a meeting of over 1,000 physicians and other oncology professionals in New York City.

Effective therapies exist, often involving combinations of chemotherapy, radiotherapy, and surgery, but long-term effects of these complex treatment regimens can negatively impact quality of life for survivors. 

Multiple studies have corroborated a survival advantage in patients with HPV-associated disease, with five-year survival of HPV-positive patients approaching 80 percent, noted Haigentz, an associate professor of Clinical Medicine at the Albert Einstein College of Medicine, Montefiore Medical Center.

Although current staging classifications do not account for HPV status, Haigentz said, HPV status is the most important prognostic factor, followed by smoking status. For example, a patient who is HPV-positive and a never or light smoker would have the best prognosis, whereas a patient who is HPV-negative and a smoker is likely to have poorer outcomes; HPV-positive smokers appear to have an intermediate prognosis, he said.

It is well established that patients with head and neck cancers have severe, acute, and frequently long-term toxicities from curative therapy, with some resulting in chronic functional impairment. These toxicities include mucositis, dysphagia (including feeding tube dependence), xerostomia, dental complications, hypothyroidism, lymphedema, and fibrosis. 

“As physicians, it is our obligation to consider any opportunity to reduce treatment morbidity in the management of these patients,” Haigentz stressed.

He suggested that HPV-associated cancers’ more favorable prognoses can set the stage for “treatment deintensification, where a gentler therapy may be sufficient to cure a patient,” underscoring that such an approach assumes treatment efficacy will be preserved. Alternatively, for poor-risk, HPV-negative patients, treatment intensification is needed. All this makes patient selection crucial, said Haigentz.

Several strategies for treatment deintensification for HPV-positive oropharyngeal cancers are under clinical evaluation, for example, replacing concurrent cisplatin with Erbitux (cetuximab) or reducing radiation doses. “Some of these studies employ selection strategies, which I think are ideal for evaluating and tailoring therapy based on personalized risk.”

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