Prevalence of high-risk human papillomavirus genotypes in retinoblastoma

Abstract

Background The human papillomavirus (HPV) is an important aetiological agent in cancer but its involvement in retinoblastomas (RBs) is controversial. Methods 64 formalin-fixed paraffin-embedded tissue blocks and 19 fresh-frozen specimens were subjected to multiplex PCR using PGMY09/11 primers, HPV genotyping, non-isotopic in situ hybridisation and immunohistochemistry for pRb and p16 INK4a . Results 24% of RBs contained HPV DNA. 90% of HPV genotypes were of high-risk (HR) type and 10% were of intermediate-risk (IR) type. HR HPVs 45, 59, 68 and 52 were detected for the first time, as were IR HPVs 82 and 73. There was only one HPV 18-positive case. Interestingly, no low-risk genotypes were identified. Nine formalin-fixed paraffin-embedded HPV-positive cases showed nuclear HPV positivity by non-isotopic in situ hybridisation. Immunohistochemistry did not show pRb expression in 67% of cases. 34% expressed nuclear p16 INK4a , of which 20 cases were also positive for HPV by multiplex PCR. A statistically significant association between HPV and pRb expression status was observed (p¼0.0001).The association of HPV with p16 INK4a expression was also statistically significant (p¼0.0001).Conclusions While the presence of HPV in a subset of RB was demonstrated, its role in carcinogenesis needs further elucidation.

Viral Perturbations of Host Networks Reflect Disease Etiology

“…The prioritized virally-implicated disease candidates (Tables S6, S7 in Text S1) indicate, for example, that malignant neoplasms of retina and bladder, ranked in the top three by the flow algorithm regarding their potential association with HPV, have relative risk 15.7 and 2.7 (Table S7 in Text S1), meaning that HPV patients have 15.7 and 2.7 times increased chance of developing these diseases. Several diseases that ranked high in our prioritization procedure are not commonly linked to the studied viruses, but their potential viral association was supported by recent suggestive reports, such as malignant neoplasm of thyroid gland association with EBV [35] and retinoblastoma association with HPV [36], [37].…”

Human papillomavirus: a predictor of better survival in ocular surface squamous neoplasia patients

“…HPV has been detected on formalin-fixed paraffin-embedded tissues by linear array in head and neck cancer and retinoblastoma cases. In retinoblastoma the detection rate was 14% in archival tissues as compared to 58% in fresh cases 21 22…”

Retinoblastoma: Recent trends A mini review based on published literature

“…[4] Recently, some HPV strains such as HPV 16, 18, 6a, 33, 11, 31, 35, and 51 have been described in fresh tumor tissue from a subset of RB patients. [56] Mohan et al found that children younger than 18 months were significantly associated with the presence of HPV DNA compared with children above 24 months in Indian patients with unilateral RB.…”

“…Another study of Asian Indians including 83 cases of unilateral RB in a population detected HPV DNA in 24% of RBs. [4] The authors stressed on the need of a multicentric study globally, to indisputably clarify the role of HPV in the etiopathogenesis of sporadic RB.…”