Mechanisms of HPV-associated tumor spread under scrutiny

By Joanna Lyford, Senior medwireNews Reporter

In patients with human papillomavirus (HPV)-associated tonsillar carcinoma, second tumors in the contralateral tonsil are typically caused by the same viral variant, a case series indicates.

The findings are helpful for understanding the molecular etiology of HPV-related head and neck squamous cell carcinomas (HNSCC), say the researchers writing in Oral Oncology.

Noting that the development of a second primary tumor in patients with HNSCC is "ominous" and "portends a poor clinical outcome," Sara Pai (Johns Hopkins Medical Institutions, Baltimore, Maryland, USA) and co-authors investigated the molecular etiology of HPV-related tumor multifocality.

From the hospital's surgical pathology archives they identified six patients with a primary HPV-related tonsillar squamous cell carcinoma who developed a synchronous or metachronous carcinoma in the contralateral tonsil.

These individuals represented just 4% of all cases of primary tonsillar carcinoma in the archives, note the authors. Of the four patients with tissue available for analysis, all were male and aged between 44 and 76 years old; three presented with synchronous tonsillar carcinomas, and one had a metachronous carcinoma.

Samples from all tumors underwent sequencing analysis for the HPV-16 E6 exon. Although specific sequence variants differed among the four patients, there was 100% concordance in HPV-16 DNA from the index and secondary primary tumor in individual patients.

Pai et al note that while the development of a secondary primary tumor has "considerable implications regarding long-term survival," all patients in this series were alive and disease-free between 6 and 13 years after diagnosis.

The finding of complete concordance in the HPV-16 E6 DNA sequence of primary and secondary tumors not only demonstrates that both were caused by the same virus variant but could also help to clarify the mechanisms by which second primary tumors develop in HPV-associated HNSCC, say the researchers.

"When a patient with an HPV-related tonsillar carcinoma develops a secondary primary tumor in the contralateral tonsil, this phenomenon of tumor multifocality does not reflect independent inoculation events with different HPV variants," they write.

"Instead, HPV-associated secondary primary tumors more likely arise from an HPV-mediated field cancerization or through clonal spread of an index carcinoma."

They add: "Although the development of secondary primary tumors does not appear to be common for patients with HPV-related tonsillar carcinomas, removal of the contralateral tonsil may disclose coincident cancers."

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