p16 Expression Correlates with Invasive Ocular Surface Squamous Neoplasms in HIV-Infected Mozambicans

Abstract

Background: p16 immunohistochemistry is widely used to diagnose human papillomavirus (HPV)-related squamous neoplasms of cervix, anogenital, head, and neck tissues. The incidence of these HPV-related squamous neoplasms is markedly increased in the HIV-infected population. Ocular surface squamous neoplasia (OSSN) is also more common in HIV-infected patients. However, the expression pattern of p16 in OSSN among HIV-infected patients is unclear. Here, we examined the expression of p16 in OSSN surgical excisions collected from a large HIV-infected cohort from ­Mozambique. Methods: OSSN surgical tissue specimens were collected from 75 Mozambican patients. Formalin-fixed, paraffin-embedded tissue blocks from these OSSNs were sectioned, stained with hematoxylin and eosin (H&E), and p16 expression by immunohistochemistry. H&E slides were reviewed to determine if OSSNs were noninvasive conjunctival intraepithelial neoplasms or invasive squamous cell carcinomas (SCC). Cases were classified as p16 positive or negative based on diffuse nuclear and cytoplasmic expression of p16 in neoplastic cells. Results: p16 positivity was found in a minority of OSSN cases (14/75). p16 positivity was significantly associated with the invasive SCC type of OSSN in HIV-infected patients (p value of 0.026). Conclusions: The majority of OSSNs in our HIV-infected cohort do not express p16. However, those cases that are p16-positive are significantly more likely to be the invasive SCC form of OSSN. We propose that p16 expression may identify more aggressive OSSNs in HIV-infected populations.

Detection of Human Papillomavirus in Squamous Lesions of the Conjunctiva Using RNA and DNA In-Situ Hybridization

“…Immunohistochemical approaches, including direct detection of HPV-encoded proteins or alterations in p16 expression, have been investigated, but more recent studies suggest that these methods are prone to false-positive results [13,22,41,46,49,51,53,55,56,58,59,82]. In particular, it has been found that many lesions negative for HPV express p16 [49,58]. Next-generation sequencing represents another potential method by which HPV would be detected in routine clinical samples [87][88][89].…”

“…Considerable variability in the correlation of HPV infection with squamous lesions has been reported, and this may be due to the variety of methods for both sampling and viral detection [31,35,46,47]. Immunohistochemical approaches, including direct detection of HPV-encoded proteins or alterations in p16 expression, have been investigated, but more recent studies suggest that these methods are prone to false-positive results in conjunctival lesions [13,22,34,41,46,[48][49][50][51][52][53][54][55][56][57][58][59]. Historically, HPV DNA was detected with Southern blotting or in-situ hybridization assays, which can have poor sensitivity, and polymerase chain reactions (PCR), with high false-positive rates [31,47].…”

Diagnostic and Therapeutic Modalities in the Management of a Patient With Ocular Surface Squamous Neoplasia (Ossn)-Case Report and Review

“…Recently Carrilho et al associated p16 as a possible marker for conjunctival SCC in HIV-positive patients. Another study classified IL-6 as a potential marker in the diagnosis of conjunctival dysplastic lesions [19,20].…”

Viral Causality of Human Cancer and Potential Roles of Human Endogenous Retroviruses in the Multi-Omics Era: An Evolutionary Epidemiology Review

“…A study conducted on a pair of monozygotic twins indicated that HIV may also cause hypermethylation, a fact which could explain the downregulation in p16 expression that can be attributed to the HIV infection (102). Ocular surface squamous neoplasia, a neoplasm related to HPV and is more common in HIVinfected individuals, demonstrates a lack of p16 expression in the majority of HIV-infected patients (103). However, the presence of p16 expression in ocular surface squamous neoplasia in HIV-infected patients predisposed to a worse prognosis (103).…”

“…Ocular surface squamous neoplasia, a neoplasm related to HPV and is more common in HIVinfected individuals, demonstrates a lack of p16 expression in the majority of HIV-infected patients (103). However, the presence of p16 expression in ocular surface squamous neoplasia in HIV-infected patients predisposed to a worse prognosis (103). All these data underline the delicate balances in the inter-viral interactions with the host and the intricate malignancy mechanisms in a setting, as such.…”