Risk factors for conjunctival squamous cell neoplasia: a matched case-control study

Abstract

Aims: To identify roles of human papillomavirus (HPV) infection and solar elastosis as the risk factors for conjunctival squamous cell neoplasia (CSCN). Methods: 30 consecutive pathological specimens, ranging from conjunctival intraepithelial neoplasia, carcinoma in situ, to invasive squamous cell carcinoma were retrieved from tissue archives. 30 controls were disease free conjunctiva from age and sex matched patients undergoing extracapsular cataract extraction. Two masked pathologists studied haematoxylin and eosin stains on paraffin embedded conjunctival tissues. Elastic stain for solar elastosis was blindly interpreted in comparison with negative and positive controls. HPV infection was studied by polymerase chain reaction and dot hybridisation. Results: The mean age of CSCN patients was 54.9 years. The male to female ratio was 1:1. Solar elastosis was seen in 53.3% of CSCN and in 3.3% of controls with an odds ratio of 16.0 (95% CI, 2.49 to 670.96; p value = 0.0003). HPV DNA were not detected in any of the specimens. Conclusion: Solar elastosis is much more frequently found in CSCN cases than in their matched controls and is a risk factor for CSCN. These data are insufficient to conclude that HPV infection is a risk factor for CSCN. C onjunctival squamous cell neoplasia (CSCN) is the most common malignant tumour of the ocular surface.1 2 The disease is prevalent in tropical areas including Thailand.3 4 Early manifestations are small masses at or around the limbus mimicking pterygia, occurring in middle aged patients. The tumours then grow slowly, invading the nearby tissues including the eyeball, eyelids, and orbital tissues leading to severe visual loss, loss of the eye, and severe facial deformities.Similar to the squamous cell carcinoma of the uterine cervix, the stagings of conjunctival squamous cell carcinoma are classified by the thickness of epithelial dysplastic changes and the tumour invasion into the substantia propria. The disease severity varies from conjunctival intraepithelial neoplasia (CIN), carcinoma in situ (CIS), to invasive squamous cell carcinoma.So far the causes of the disease are not adequately understood. There have been a number of investigations on the relation between the tumour to several factors, including solar exposure 5-7 and human papillomavirus (HPV). 8-12Solar exposure has been observed to cause the epithelial malignancy. Newton et al 5 related the prevalence of this malignancy to tropical location of the patient dwellings. Sun et al 6 found an association between ultraviolet exposure and the prevalence of squamous cell neoplasia of the conjunctiva and the eyelids. However, these two studies were conducted as non-comparative studies. Lee et al 7 found a relation of sun exposure to squamous cell dysplasia in a case-control study, but did not include the pathological study on the actinic damage of the tissue.A number of studies have been successful in detecting HPV type 16 and 18 in CSCN. [8][9][10][11][12] However, benign conjunctival lesions have been shown to contain the ...

The evaluation of human papillomavirus and p53 gene mutation in benign and malignant conjunctiva and eyelid lesions.

“…Similar to Matsumoto et al [6], Toth at al. [8] and Eng et al [9] in the recent studies the HPV presence in squamous carcinomas ranged from 86% (Ateenyi-Agaba et al [10]) to 0% (Eng et al [9], Newton et al [12], and Tulvatana et al [11]). In our study a very low percentage of HPV-positive cases might indicate other than viral etiology of benign and malignant lesions of the conjunctiva and eyelid.…”

Solar and ultraviolet radiation

“…Cumulative years of life in which > 50% of daytime was spent outdoors were similarly but more weakly associated with ocular surface epithelial dysplasia. Tulvatana et al (2003) studied 30 cases of conjunctival squamous cell neoplasia (intraepithelial or invasive) and 30 age-and sex-matched control patients having extracapsular cataract extraction from whom diseased conjunctiva was taken [site of biopsy not specified]. Solar elastosis [representing pathologically proven solar damage] was observed in the conjunctiva of 53% of cases and 3% of controls, resulting in an odds ratio of 16.0 (95%CI: 2.49-671).…”

Ocular Surface Squamous Neoplasia

“…(Scott et al 2002) In contrast, several studies have failed to demonstrate HPV in malignant conjunctival epithelial tumors and suggested that HPV was not associated with malignant conjunctival lesions and posed other mechanism, such as UVB being more important to the etiology of these lesions. (Eng et al 2002;Tulvatana et al 2003;Sen et al 2007;Manderwad et al 2009) Thus, the association between HPV and OSSN is variable in different geographic areas, and perhaps depends on the method of detection used. (Eng et al 2002;Sen et al 2007;Guthoff et al 2009;Manderwad et al 2009) …”

“…(Ateenyi-Agaba et al 2004) Solar elastosis was also found more frequently in pathological specimens from the conjunctival squamous cell neoplasia (53.3% of cases and 3.3% of controls). (Tulvatana et al 2003) One immunohistochemical study showed that UV radiation may play a role as a stimulating agent in the expression of some proteolytic enzymes, such as matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs), which are relevant to neoplasia. (Ng et al 2008) www.intechopen.com…”