No Evidence for a Pathogenic Role of Human Papillomavirus Infection in Ocular Surface Squamous Neoplasia in Germany
Rainer Guthoff, Alexander Marx, Phillipp Stroebel
Overview:
The paper that I have chosen is about Ocular Surface Squamous Neoplasia (OSSN). This is a rare condition that consists of both non-invasive and invasive squamous tumors of the conjunctiva and the cornea.
The origin and causation of OSSN is unclear, but it is known that UV exposure is a risk factor for cellular damage.
There is a greater occurrence of this disease near the equator.
It has been found that co-infection with immunodeficiency diseases -HIV- increases the risk for OSSN by a 10 fold.
The high risk HPV-E6 protein can cause degradation of p53, which is a tumor suppressive protein, and acts as a major cell cycle checkpoint.
Degradation of this protein will restrain the oncosuppressive function of p53.
When DNA damage occurs, p53 levels increase, which induces a rise in the expression of p21. The increased level of p21 will block the progression of cell cycle into the G1 phase.
If cell damage is beyond repair, p53 can then induce apoptotic cell death.
If p53 function is lost, p21 is not induced, and malignant tumors frequently occur.
In this study, they evaluated potential risk factors of OSSN, such as UV damage and HPV infection.
They included all lesions that were treated by the Department of Opthamology, at the University of Wuerzburg, from 1995-2002.
Samples were obtained from 26 males and 5 females, all were Caucasian, with a median age of 70.
There was no history of HIV in any of the cases.
Histological slides of all specimens were re-evaluated by one of the authors, and graded. The grading of the neoplasia was based on severity of dysplasia at single cell level, and as well as overall architecture of the tissue.
5 conjunctival specimens with no conjunctival disease were used as controls.
Cells were stained with Hematoxylin and Eosin, as well as Elastica van Geisons.
They also used Multiplex Fluorescent PCR for HPV typing, and used immunohistochemistry for identification of certain cell types.
Results
Solar elastosis, which is the degeneration of elastic tissue, due to UV damage, was not detected in the normal control samples, but was present in 68% of OSSN specimens.
HPV was not detected in any OSSN sample by either immunohistochemistry or multiplex PCR.
Expression of p53 was more frequent in OSSN specimens (81%) when compared to control specimens (60%).
p53 expression without upregulation of p21 was also observed in 19% of OSSN cases, and 0% of the controls.
After analyzing the results of this paper, it was found that HPV infection is not involved in the development of the vast majority of OSSN cases in Germany.
The origin and cause of OSSN may differ between industrial and developing countries, because HPV infection has been shown to be a strong risk factor for squamous cell carcinomas in equatorial countries such as Tanzania and Uganda.
This study proved that solar elastosis from chronic UV exposure was common in OSSN patients (68%).
It was also found that the p53 gene was mutated in roughly 20% of OSSN cases, which also plays a large role in the development of tumors.
SO: Major factor for development of OSSN in the German population is UV EXPOSURE!!!
Important life lesson= Wear your sunglasses and protect your eyes from harmful UV rays! :)
Critique:
This was a fairly well written paper, but I feel like they left out a lot of important information. Firstly, they mentioned terms such as the "ubiquitin-protease pathway", and "caspase activation". They just mentioned these terms assuming that the reader would know what they are talking about. When they mentioned that they performed Multiplex PCR and Immunohistochemistry, they did not mention the procedure of these techniques, they just stated which compounds they used. They did not include a lot of histological representation of the tissues, and in the pictures that they did show, nothing was explained. They also treated the tissues with various antibodies, for the immunohistochemistry, and they just briefly listed the antibodies. They did not think that it was necessary to explain what they were for, and I just found it a little bit confusing when trying to look at the results. I feel like further studies need to be conducted on this topic to determine the real cause of OSSN, because it seemed like they just threw this experiment together, and came up with the conclusion that UV exposure is the main risk factor for this disease.
I found the topic of this paper to be very interesting, and I think that if more research is done on the subject, it could be very helpful to finding ways to prevent Ocular Surface Squamous Neoplasia.
LINK TO PAPER
They included all lesions that were treated by the Department of Opthamology, at the University of Wuerzburg, from 1995-2002.
Samples were obtained from 26 males and 5 females, all were Caucasian, with a median age of 70.
There was no history of HIV in any of the cases.
Histological slides of all specimens were re-evaluated by one of the authors, and graded. The grading of the neoplasia was based on severity of dysplasia at single cell level, and as well as overall architecture of the tissue.
5 conjunctival specimens with no conjunctival disease were used as controls.
Cells were stained with Hematoxylin and Eosin, as well as Elastica van Geisons.
They also used Multiplex Fluorescent PCR for HPV typing, and used immunohistochemistry for identification of certain cell types.
Results
Solar elastosis, which is the degeneration of elastic tissue, due to UV damage, was not detected in the normal control samples, but was present in 68% of OSSN specimens.
HPV was not detected in any OSSN sample by either immunohistochemistry or multiplex PCR.
Expression of p53 was more frequent in OSSN specimens (81%) when compared to control specimens (60%).
p53 expression without upregulation of p21 was also observed in 19% of OSSN cases, and 0% of the controls.
After analyzing the results of this paper, it was found that HPV infection is not involved in the development of the vast majority of OSSN cases in Germany.
The origin and cause of OSSN may differ between industrial and developing countries, because HPV infection has been shown to be a strong risk factor for squamous cell carcinomas in equatorial countries such as Tanzania and Uganda.
This study proved that solar elastosis from chronic UV exposure was common in OSSN patients (68%).
It was also found that the p53 gene was mutated in roughly 20% of OSSN cases, which also plays a large role in the development of tumors.
SO: Major factor for development of OSSN in the German population is UV EXPOSURE!!!
Important life lesson= Wear your sunglasses and protect your eyes from harmful UV rays! :)
Critique:
This was a fairly well written paper, but I feel like they left out a lot of important information. Firstly, they mentioned terms such as the "ubiquitin-protease pathway", and "caspase activation". They just mentioned these terms assuming that the reader would know what they are talking about. When they mentioned that they performed Multiplex PCR and Immunohistochemistry, they did not mention the procedure of these techniques, they just stated which compounds they used. They did not include a lot of histological representation of the tissues, and in the pictures that they did show, nothing was explained. They also treated the tissues with various antibodies, for the immunohistochemistry, and they just briefly listed the antibodies. They did not think that it was necessary to explain what they were for, and I just found it a little bit confusing when trying to look at the results. I feel like further studies need to be conducted on this topic to determine the real cause of OSSN, because it seemed like they just threw this experiment together, and came up with the conclusion that UV exposure is the main risk factor for this disease.
I found the topic of this paper to be very interesting, and I think that if more research is done on the subject, it could be very helpful to finding ways to prevent Ocular Surface Squamous Neoplasia.
LINK TO PAPER
