Human papillomavirus in normal conjunctival tissue and in conjunctival papilloma: Types and frequencies in a large series

Eye Pathology Institute, University of Copenhagen, Frederik V's Vej 11, DK-2100 Copenhagen Ø, Denmark.
British Journal of Ophthalmology (Impact Factor: 2.98). 09/2007; 91(8):1014-5. DOI: 10.1136/bjo.2006.108811
Source: PubMed


To examine conjunctival papilloma and normal conjunctival tissue for the presence of human papillomavirus (HPV).
Archival paraffin wax-embedded tissue from 165 conjunctival papillomas and from 20 histological normal conjunctival biopsy specimens was analysed for the presence of HPV by PCR. Specimens considered HPV positive using consensus primers, but with a negative or uncertain PCR result using type-specific HPV probes, were analysed with DNA sequencing.
HPV was present in 86 of 106 (81%) beta-globin-positive papillomas. HPV type 6 was positive in 80 cases, HPV type 11 was identified in 5 cases and HPV type 45 was present in a single papilloma. All the 20 normal conjunctival biopsy specimens were beta-globin positive and HPV negative.
There is a strong association between HPV and conjunctival papilloma. The study presents the largest material of conjunctival papilloma investigated for HPV and the first investigation of HPV in normal conjunctival tissue. HPV types 6 and 11 are the most common HPV types in conjunctival papilloma. This also is the first report of HPV type 45 in conjunctival papilloma.

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    • "HPV has also been identified as a possible contributing factor [40], [41]. However, benign conjunctival lesions have been shown to contain the infections as well [46], [47]. Moreover, recent studies have demonstrated a zero or low frequency of HPV DNA-positive cases [48], [49]. "
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    ABSTRACT: The leucine rich repeats and immunoglobulin-like protein 1 (LRIG1) is a newly discovered negative regulator of epidermal growth factor receptor (EGFR) and a proposed tumor suppressor. It is not universally downregulated in human cancers, and its role in neoplastic transformation and tumorigenesis is not well-documented. In this study, we show the expression of LRIG1 as a novel potential marker for neoplastic transformation in ocular-surface squamous neoplasia (OSSN). The following two groups were included in this study: 1) benign group (3 cases; 1 with papilloma and 2 with dysplasia) and 2) malignant group (3 cases with squamous cell carcinoma (SCC)). In both groups, immunofluorescence analysis was firstly performed for keratins 4, 12, 13, and 15 to characterize the state of differentiation, and for Ki67 to evaluate the proliferation activity. Subsequently, LRIG1 and EGFR expression was analyzed. Either keratin 4 and/or 13, both non-keratinized epithelial cell markers, were generally expressed in both groups, except for 1 severe SCC case. Keratin 15, an undifferentiated basal cell marker, was more strongly expressed in the malignant cases than in the benign cases. The Ki67 index was significantly higher (P<0.002) in the malignant group (33.2%) than in the benign group (10.9%). LRIG1 expression was limited to basal epithelial cells in normal corneal epithelial tissue. Interestingly, LRIG1 was expressed throughout the epithelium in all the benign cases. In contrast, its expression was limited or totally disappeared in the malignant cases. Inversely, EGFR staining was faintly expressed in the benign cases, yet strongly expressed in the malignant cases. Malignant tissue with proliferative potential presented EGFR overexpression and inverse downregulation of LRIG1, consistent with LRIG1 being a suppressor of neoplastic transformation by counteracting the tumor growth property of EGFR. Our findings indicate that downregulation of LRIG1 is possibly a novel potential marker of transformation and tumorigenesis in OSSN cases.
    PLoS ONE 04/2014; 9(4):e93164. DOI:10.1371/journal.pone.0093164 · 3.23 Impact Factor
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    • "HPV 16 and HPV 18 are responsible for more than 70% of cervical cancers followed by other HR HPV types. Other types found in conjunctival papillomas in case reports are HPV 33, HPV 45, and HPV 13.15,22,23 "
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    ABSTRACT: We describe two patients with squamous cell papilloma of the conjunctiva due to human papilloma virus (HPV) and review the literature. Two patients with conjunctival tumors were examined and treated in the University Eye Clinic and diagnosed in the University Pathology Department, University Hospital of Ioannina, Greece. The first patient was a 48-year-old man presenting with an extended papillomatous lesion in bulbar conjunctiva covering part of the cornea of his right eye. The second patient was a 24-year-old man presenting with a polypoidal papillomatous lesion on the caruncle of his right eye. The two lesions were removed surgically, cryotherapy was applied to the adjacent conjunctiva, and topical mitomycin-C was used. The amniotic membrane was used to restore the conjunctival defect in the first patient. The two removed lesions were sent to the Pathology Department for histopathological examination. Immunohistochemistry, DNA in situ hybridization, and polymerase chain reaction (PCR) analysis were performed. In the first patient, histopathology showed the presence of a benign squamous papilloma with koilocytosis. DNA in situ hybridization with broad-spectrum probes showed that this patient was positive for HPV DNA. In the second patient, histopathology showed the presence of a squamous papilloma with mild dysplasia and koilocytosis. Immunohistochemical analysis was positive for HPV protein and p16 protein. DNA in situ hybridization with broad-spectrum probes showed that the patient was positive for HPV DNA. PCR analysis showed the presence of HPV 6. According to morphological and molecular findings, both patients were diagnosed with squamous cell papilloma due to HPV. HPV can infect the ocular surface. According to clinical results, the ophthalmologist in cooperation with the pathologist can recommend appropriate laboratory examinations to confirm the diagnosis and successfully treat conjunctival papillomas.
    Clinical Ophthalmology 09/2012; 6(1):1553-61. DOI:10.2147/OPTH.S34999 · 0.76 Impact Factor
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    • "Etiological factors include ultraviolet light, smoking, HPV infection and immunodeficiency. The presence of multiple lesions is especially suggestive of an infection with HPV; subtypes 6,11,16,18 and 33 are the commonest ones (Peck et al., 2006; Sjo et al., 2007). "
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    ABSTRACT: A 31-year-old Black man presented with two oval masses in his right conjunctiva. The tumors were completely excised and histology showed that the inferior lesion was a conjunctival squamous papilloma with pigmentation while the superior one was an inverted conjunctival papilloma, which grew in an endophytic manner. Follow up examination one year later showed no recurrence. Literature search revealed no previous report of simultaneous appearance of these types of papilloma in the same eye. Management of conjunctival squamous papillomas is difficult and is complicated by multiple recurrences in contrast to inverted conjunctival papillomas where no recurrences have been reported after complete excision. Thus, histopathology is an absolute necessity even when papillomas appear in the same eye.
    Orbit (Amsterdam, Netherlands) 10/2010; 29(5):266-8. DOI:10.3109/01676831003739707
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