Human papillomavirus infection plays a role in conjunctival squamous cell carcinoma: a systematic review and meta‐analysis of observational studies

Abstract

Purpose We aimed to study the prevalence of human papillomavirus (HPV) in conjunctival intraepithelial neoplasia and carcinoma. Furthermore, we aimed to explore whether geographical differences or different detection modalities are associated with the conflicting information regarding HPV and the development of the disease. Methods We searched the MEDLINE, EMBASE and Scopus databases for studies reporting on HPV and conjunctival intraepithelial neoplasia or carcinoma. The pooled prevalence proportions, odds ratio (OR) and corresponding 95% confidence intervals were calculated assuming a random‐effects model. Subgroup analyses and meta‐regression explored possible sources of heterogeneity. Results A total of 39 studies were included in the systematic review. The pooled prevalence of HPV in conjunctival intraepithelial neoplasia and carcinoma was 26%, with HPV16, 18, and 33 being the most frequently reported genotypes. Human papillomavirus (HPV) infection was associated with an increased risk of conjunctival intraepithelial neoplasia and carcinoma (OR 8.4, 95% confidence interval (CI) 3.7–19.1); lower in studies from African countries (OR 1.7, 95% CI 0.9–3.5) than other countries (OR 16.1, 95% CI 5.8–44.3), p = 0.013. Conclusion Human papillomavirus infection increases the odds of conjunctival intraepithelial neoplasia and carcinoma by 8.4 compared to healthy conjunctival mucosa or other ocular surface diseases. There seem to be geographical differences regarding HPV in conjunctival intraepithelial neoplasia and carcinoma. HPV16 was the most prevalent genotype, followed by HPV18 and HPV33, meaning that most of the HPV‐related conjunctival intraepithelial neoplasia and carcinoma may be prevented by the HPV vaccines that are currently available.

Human Papillomavirus Related Neoplasia of the Ocular Adnexa

“…Increasing evidence also supports the role of HPV in conjunctival CIN and SCC, and HPV status may also serve as an important biomarker in these diseases. With an odds ratio (OR) 8.42 (95%CI 3.70–19.16 in 21 studies) [ 35 ] and a risk ratio (RR) 3.13 (95%CI 1.72–5.71, 16 studies) [ 36 ] in two separate meta-analyses based on observational studies, HPV has shown to be strongly associated with an increased risk of conjunctival CIN and SCC. The prevalence estimates of HPV are 26% (95%CI 13–42%) in conjunctival CIN and 18% (95%CI 7–32%) in invasive SCC compared to 1% (95%CI 0–3%) among controls [ 35 ].…”

“…With an odds ratio (OR) 8.42 (95%CI 3.70–19.16 in 21 studies) [ 35 ] and a risk ratio (RR) 3.13 (95%CI 1.72–5.71, 16 studies) [ 36 ] in two separate meta-analyses based on observational studies, HPV has shown to be strongly associated with an increased risk of conjunctival CIN and SCC. The prevalence estimates of HPV are 26% (95%CI 13–42%) in conjunctival CIN and 18% (95%CI 7–32%) in invasive SCC compared to 1% (95%CI 0–3%) among controls [ 35 ]. An overview of studies examining HPV in conjunctival intraepithelial neoplasia and carcinoma (39 studies) is provided in a recently systematic review by our group [ 35 ].…”

“…The prevalence estimates of HPV are 26% (95%CI 13–42%) in conjunctival CIN and 18% (95%CI 7–32%) in invasive SCC compared to 1% (95%CI 0–3%) among controls [ 35 ]. An overview of studies examining HPV in conjunctival intraepithelial neoplasia and carcinoma (39 studies) is provided in a recently systematic review by our group [ 35 ].…”

“…Further, the loss of HPV E4 gene expression in the malignant cells, hence a transition from a productive to an abortive life-cycle of the HPV, is documented in a series of conjunctival CIS similar to high-risk cervical intraepithelial neoplasia [ 33 ]. The high-risk genotype HPV16 is by far the most frequent genotype in conjunctival CIN and SCC, followed by HPV18 and HPV33 [ 35 ]. Less frequent, HPV6, 11, 31, 35, 37, 39, 44, 45, 51, 52, 58, 66, 72, and 83, are detected [ 35 ].…”

“…The high-risk genotype HPV16 is by far the most frequent genotype in conjunctival CIN and SCC, followed by HPV18 and HPV33 [ 35 ]. Less frequent, HPV6, 11, 31, 35, 37, 39, 44, 45, 51, 52, 58, 66, 72, and 83, are detected [ 35 ].…”