Clinical characteristics, HIV status, and molecular biomarkers in squamous cell carcinoma of the conjunctiva in Ghana

Abstract

Background and aims: Conjunctival squamous cell carcinoma (CSCC) varies in incidence geographically from 0 to 1 case per 100 000 per year globally. Additionally, the incidence of CSCC is known to increase 49% for every 10° decrease in latitude. Since the onset of the AIDS epidemic, there has been a trend of increasing incidence of CSCC in Africa, and despite relatively stable levels of ultraviolet (UV) exposure, there is an observed 12 times greater risk of developing CSCC when individuals are infected with HIV. In this study, we aim to analyze the clinical characteristics and biomarkers of CSCC in Ghana.

Methods: In this study, a registry review of patients from January 2011 to May 2016 with CSCC at Komfo-Anokye Teaching Hospital in Kumasi, Ghana, was performed (n = 64). Tumor blocks of the CSCC were analyzed for the expression of various biomarkers.

Results: In this study, the median age of onset of CSCC is 46.5 years old (range of 20-90 y old). Fifty one and a half percent (n = 33) of the cohort is female. There is a low rate of smoking and alcohol use in our CSCC cohort. Thirty-nine percent (n = 12) of Ghanaian men with CSCC are HIV-, while only 12% (n = 4) of women are HIV-. Fifteen patients had metastasis to lymph nodes or other tissues, and we observed a statistically significant relationship between HIV infection and metastasis (P = 0.027, chi-squared test). We observed no statistically significant relationship between known prognostic CSCC biomarkers and HIV status, age, or tumor stage.

Conclusion: Better characterization of CSCC could have a profound impact on the prevention, early identification, and treatment of CSCC in Africa. A retrospective chart analysis and collection of tumor samples can be challenging in this region due to methods of record keeping and stigma attached to clinical data such as HIV testing and smoking and alcohol use. As a result, in this study, data were often incomplete leading to inconclusive results and analysis that should be interpreted with caution. Future studies should consider a prospective study design that gathers clinical data in a standardized format and ensures fresh tissue from CSCC tumors.

Keywords: CSCC; Ghana; HIV/AIDS; viral oncology.

Figure 1

Age and HIV status at diagnosis. The ages are arranged in bins of 5 years, and the HIV status is indicated by the colors. We observed no statistically significant relationship between age at diagnosis and sex or between age at diagnosis and HIV status (logistic regression, P = 0.419; P = 0.241, respectively). However, we note that no patient below age 35 had a positive HIV test

Figure 2

Symptoms on initial presentation. Patient symptoms on initial presentation with conjunctival squamous cell carcinoma (CSCC). The most common complaint was the presence of a mass (n = 43) followed by discharge (n = 35), pain (n = 26), swelling (n = 19), vision changes (n = 19), eye discoloration (n = 18), and itching (n = 15)

Figure 3

Presence of tumor biomarkers stratified by HIV status. The results of the tumor biomarker analysis are graphed and stratified by HIV status. All 59 CSCC samples were analyzed for p53, p16, EGFR, and cyclin D, but not every sample yielded a result for every biomarker. As such, the number of samples within each biomarker graph does not always add up to 59. We observed no significant relationship between any of the tumor biomarkers and HIV status, sex, or stage of the tumor. However, only 27 samples had corresponding clinical data

Figure 4

Immunostaining does not correlate with human papillomavirus (HPV) status in our conjunctival squamous cell‐carcinoma (CSCC) cohort. Four independent replicates of immunohistochemical staining with parallel positive and negative control tissue were performed per sample, and representative images from p16 and p53 staining from an HPV positive case and HPV negative case are shown. We expected to observe p53 expression in the HPV negative cases and p53 suppression in HPV positive cases as p53 is known to be suppressed in HPV infection. Indeed, p53 expression is seen in the HPV negative cases, and p53 suppression is seen in the HPV positive case. Additionally, we expected to see p16 expression in the HPV positive case as p16 is a frequent marker of HPV infection in cells. However, p16 is negative in both the HPV positive case and HPV negative case. It is possible that p16 expression is not an accurate marker for HPV infection in these samples