NEW YORK (Reuters Health) – Co-localization of human papillomavirus (HPV) in the tonsils’ bacterial biofilm may play a role in the pathogenesis of HPV-related oropharyngeal cancer, researchers suggest.
That cancer “is increasing in incidence at a dramatic pace,” Dr. Matthew Miller of Strong Memorial Hospital in Rochester, New York, told Reuters Health. “While it is known that HPV exposure is nearly universal by mid-adulthood, only a small proportion of those infected will ever develop an oropharyngeal cancer.”
“Though the molecular biology of HPV-related tumorigenesis is well established,” he said by email, “the mechanisms by which HPV escapes immune surveillance and gains entry to the tonsillar/tongue base cells has to this point been unclear.”
“This study demonstrates that despite high rates of HPV seropositivity among the general population, the rates of asymptomatic carriage are actually quite low among healthy young adults,” he added.
“Importantly, however, when carried in asymptomatic individuals, the virus appears to associate itself with extracellular biofilm in the base of the tonsil crypts,” he noted. “It is postulated that this may serve as a protective environment and reservoir for re-infection and subsequent tumorigenesis years or even decades later.”
To investigate, Dr. Miller and colleagues retrospectively assessed tonsil samples obtained after elective non-cancer tonsillectomy from 102 adults ages 20 to 39 (54% women). Samples with HPV were then analyzed to localize the viral capsid protein and establish the presence of biofilm.
As reported online January 25 in JAMA Otolaryngology-Head and Neck Surgery, the overall prevalence of HPV in tonsils from these otherwise healthy adults was 4.9% (five samples); the prevalence of high-risk type 16 or 18 was 3.9% (four samples). In situ hybridization demonstrated that HPV co-localized to the biofilm of the tonsillar crypts.
The finding “has important implications with respect to the determination of HPV prevalence rates in the oropharynx (and) may also play a role in the pathogenesis of HPV-related oropharyngeal carcinoma,” the authors conclude.
Dr. Miller said, “Identification of HPV in a biofilm-associated, potentially latent state implies that the virus may avoid immune detection and clearance even in seropositive individuals – essentially allowing it to be an ‘oncovirus in waiting.’”
“If a reliable screening tool were developed – oral rinses are being investigated presently – to identify these carriers,” he said, “subsequent efforts might be aimed at creation of topical antimicrobials that would disrupt the biofilm and allow for elimination of the virus.”
“Given the lack of universal HPV immunization and the potential for the virus to escape immune surveillance even in seropositive individuals,” he continued, “this has potentially far-reaching implications for prevention of oropharyngeal carcinoma.”
“One drawback of the study is that given its retrospective nature, we do not know the seroprevalence of HPV positivity in our sample or, specifically, the individuals whose specimens contained HPV DNA,” he acknowledged. “In addition, given the age range of our subjects, it is also feasible that these represent primary HPV infections rather than carrier states.”
“Electron microscopy follow-up studies are planned to better establish the relationship between the HPV virions and the biofilms,” Dr. Miller said. “Future studies to correlate HPV oral rinse findings to histology/ISH (are planned).”
Dr. Seungwon Kim, a head and neck surgeon at UPMC Hillman Cancer Center in Pittsburgh, told Reuters Health, “It is unclear why some patients are able to clear the HPV after the initial exposure and why some patients cannot.”
“This study suggests that the biofilm layer may harbor a reservoir of HPV that is shielded from clearance by the immune system,” he said in an email.
“Although the study offers a possible explanation for the selective persistence of HPV in certain patients, the significance of the findings is unclear,” he concluded. “Much more work is needed before definitive associations can be (established).”
SOURCE: http://bit.ly/2Eiq5UA
JAMA Otolaryngol Head Neck Surg 2018.
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