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HPV DNA in conjunctival papillomas. Comparison of published data
Source publication
To examine conjunctival papillomas for the presence of human papillomavirus (HPV) and koilocytosis.
Archival paraffin embedded tissue from 55 conjunctival papillomas was analysed for the presence of HPV by polymerase chain reaction and subsequent filter hybridisation. Histological sections of the 55 papillomas were evaluated for the presence of koi...
Contexts in source publication
Context 1
... authors have analysed conjunctival papillomas for presence of HPV, and HPV types 6, 11, and 16 have been demonstrated (Table 2). The previously published material has either been small or less sensitive tech- niques have been applied (Table 2). ...
Context 2
... authors have analysed conjunctival papillomas for presence of HPV, and HPV types 6, 11, and 16 have been demonstrated (Table 2). The previously published material has either been small or less sensitive tech- niques have been applied (Table 2). Using the PCR technique with consensus primers we demonstrated HPV in 48 of 52 papillomas (92%). ...
Similar publications
Human papilloma virus (HPV) types 16 and 18 have been associated with neoplastic conditions of the conjuctiva. However, the presence of this virus has not been reported in non-neoplastic disorders of the external eye nor has it been studied in normal conjunctival tissues.
Ninety six paraffin embedded tissue specimens with neoplastic and non-neoplas...
Citations
... Depending about different HPV subtypes which are associated with benign or malignant epithelial tumors; for example, HPV 6 and 11 are associated with benign neoplasia while HPV 16 and 18 are closely linked with malignancy of the uterine cervical squamous epithelium [18]. On the other hand, HPV is also associated with epithelial tumors of the conjunctiva, including conjunctival papilloma [19] and conjunctival carcinoma. (McDonnell et al., 1992) [20]. ...
Pterygium is one of the most frequent pathologies in ophthalmology, and is a benign, overgrowth of fibrovascular tissue, often with a wing-like appearance, from the conjunctiva over the cornea. It is composed of an epithelium and highly vascular, sub-epithelial, loose connective tissue. There is much debate surround the pathogenesis of pterygium and a number of theories have been put forward including genetic instability, cellular proliferation, inflammatory influence, and degeneration of connective tissue, angiogenesis, aberrant apoptosis and viral infection. At present, the involvement of human papillomavirus (HPV) in the genesis of pterygium is controversial, as have reported that HPV is present in 58% of cases, while others have failed to detect HPV in pterygium. In this study, we evaluated the presence and viral genotype of HPV DNA in pterygia and healthy conjunctiva sample, and virus integration into the cellular genome.
Forty primary pterygia samples and 12 healthy conjunctiva samples were analyzed to HPV DNA presence by polymerase chain reaction, using MY09/MY11 primers of HPV-L1 gene. Viral genotype was identified by DNA sequence analysis of this amplicon. HPV integration into the cellular genome was analyzed by western blot detecting HPV-L1 capsid protein.
Presence of HPV was observed in 19 of the 40 pterygia samples. In contrast, healthy conjunctiva samples were negative. To determine virus type, sequence analyses were performed. Interestingly, 11 out of the 19-pterygium samples were identified as HPV-11 type, meanwhile, the remaining 8 pterygium samples were identified as HPV-18. HPV-L1 capsid protein were found only in 3 out of the 10 samples studied.
In conclusion, our study identified the presence of HPV DNA exclusively in pterygium samples and described HPV-11 and -18 genotypes. Our results suggest that HPV may be involved in the pathogenesis of pterygium. On the other hand, the expression of the L1-HPV protein suggests viral integration into the cellular genome.
... It usually appears as a sessile or pedunculated hoary or flesh-colored neoplasm and might be related to human papillomavirus (HPV) infection. Other studies have also revealed the possible relationship between ocular papilloma and ultraviolet irradiation, chemical exposure, ocular trauma, and immune deficiency [1][2][3][4][5][6][7]. For many years, ophthalmologists have considered it a widespread benign tumor in the ocular region. ...
Purpose
This study aimed to analyze the clinicopathological features of ocular papilloma, a common benign tumor, and the risk factors related to its recurrence and partial deterioration.
Methods
We collected and analyzed the clinical information of 298 patients (51.68% males) with mean age of 41.54 ± 21.95 years, in the ophthalmology department of the West China Hospital. Clinical and pathological factors that might be related to papilloma recurrence and partial deterioration were studied.
Results
The top three papilloma sites were bulbar conjunctiva, eyelid skin and palpebral conjunctiva. Moreover, 3.59% of lesions presented a malignant transformation, and 16.28% of patients had one or more recurrences after an average follow-up of 4.47 years. The multivariate logistic regression model showed that multiple lesions were a risk factor for recurrence (p = 0.022, OR = 3.088, 95% CI: 1.180–8.079), while cryotherapy decreased the recurrence risk (p = 0.044, OR = 0.364, 95% CI: 0.136–0.972). Additionally, elderly patients and lesions on the corneal limbus or cornea had a higher risk of malignant transformation (p = 0.004 and 0.01, OR = 1.086 and 7.827, 95% CI: 1.027–1.150 and 1.629–37.596, respectively).
Conclusion
Ocular papilloma usually occurs in middle-aged and young patients, with no significant gender differences. Older patients and lesions on the corneal limbus or cornea are risk factors for partial malignant transformation. Finally, multiple lesions were a risk factor for recurrence, and cryotherapy reduced the recurrence rate.
... A link with human papillomavirus (HPV), particularly 6 and 11, has been established. 17 In accordance with the literature, benign squamous papilloma was the second most common lesion in our case series; in addition, it was more frequent in younger patients (mean age of 37 years). ...
Background/Aims
To review the clinicopathological features of caruncle biopsies carried out at a district general hospital in the United Kingdom (UK), and compare with other centres where data has been published.
Methods
Retrospective, single-centre, observational case series between 2004–2020.
Results
A total of 31 lesions from 31 patients were analysed. 18 of 31 patients were men (58%), and the age ranged from 12 to 91 years. 13 different histopathological types of lesions were identified in our case series, including 9 melanocytic nevi (29%), 7 benign squamous papillomas (23%), 5 skin adnexal lesions (16%), 3 chronic inflammation (10%), 3 epithelial cysts (10%), 1 basal cell carcinoma (3%), 2 malignant melanomas (6%) and l lymphoproliferative disorder (3%). Pre-operative suspected diagnoses were often vague but correct in 12 of 18 cases (67%), where data was available.
Conclusion
The uncommon nature and variety of caruncular lesions make the diagnostic process difficult. Our case series is the first reported in the UK, showing a slightly higher proportion of malignant melanomas, in keeping with the population demographics. Excisional biopsies would, therefore, be prudent in the majority of cases to rule out any possible malignancy.
... Junginės papilomas dažniausiai (44,4 -75,4%) sukeliantys ŽPV tipai yra 6 ir 11 (pagal onkogeniškumą priskiriami žemos vėžio rizikos grupei) [2,3]. Infekuota ŽPV motina virusą gali perduoti vaikui gimdymo metu, taip pat infekcija plinta per kontaminuotus paviršius, rankas [4]. Virusas perduodamas lytiniu keliu, esant tiesioginiam kontaktui [5]. ...
Tikslas – išanalizuoti junginės papilomų klinikinius požymius, diagnostikos ir gydymo principus. Tyrimo metodas – sisteminė literatūros apžvalga. Mokslinių publikacijų paieška atlikta naudojantis PubMed paieškos sistema elektroninėje Medline duomenų bazėje. Atrinkti straipsniai, parašyti anglų kalba. Rezultatai. Junginės papilomos auga egzofitiškai, endofitiškai arba mišriai. Dažniausiai jos apibūdinamos kaip epitelio išaugėlės, kabančios ant plonos kojelės. Šiuolaikinėje oftalmologijoje naviko diagnozavimui dažniausiai naudojamas nesąlytinis, neinvazinis tyrimas – optinė koherentinė tomografija. Junginės papilomos gydomos konservatyviai arba chirurginiu būdu. Išvados. Junginės papilomos turėtų būti diagnozuojamos neinvaziniais tyrimo būdais, tokiais kaip OKT. Itin svarbu riboti invazinius tyrimus dėl papilomų išsisėjimo rizikos. Jeigu gydant tik konservatyviai, nepavyksta efektyviai išgydyti junginės papilomų, tikslinga taikyti chirurginius gydymo metodus. Gydant papilomas tradiciniu chirurginiu būdu, atliekant plačią eksciziją, geriausių gydymo rezultatų siekiama taikant papildomus gydymo metodus (krioterapiją/ CO2 lazerį/ vietinę chemoterapiją).
... Histopathologically, the presence of basaloid cells, intraepithelial goblet cells, a non-keratinizing squamous epithelium, and lack of solar elastosis are associated with HPV [9]. On the other hand, koilocytosis is not a valid biomarker for HPV-related conjunctival papilloma [8,11,14]. Clinically, a location of a papilloma other than at the corneal limbus is associated with HPV infection [9]. A prognostic and predictive value of HPV status in conjunctival papilloma is not yet determined. ...
Human papillomaviruses (HPV) are a large group of DNA viruses that infect the basal cells of the stratified epithelium at different anatomic locations. In the ocular adnexal region, the mucosa of the conjunctiva and the lacrimal drainage system, as well as the eyelid skin, are potential locations for HPV-related neoplasia. The role of HPV in squamous cell neoplasia of the ocular adnexa has been debated for several decades. Due to the rarity of all these tumors, large studies are not available in the scientific literature, thereby hampering the precision of the HPV prevalence estimates and the ability to conclude. Nevertheless, increasing evidence supports that defined subsets of conjunctival papillomas, intraepithelial neoplasia, and carcinomas develop in an HPV-dependent pathway. The role of HPV in squamous cell tumors arising in the lacrimal drainage system and the eyelid is still uncertain. Further, the potential of HPV status as a diagnostic, prognostic, or predictive biomarker in these diseases is a topic for future research.
... It is strongly associated with HPV [5] (mostly type HPV11). [6,7] Other types of virus have also been found: type 6 (group with low oncogenic potential-benign lesion) [8] and type 16, 18, or 45 (group with high oncogenic potential-associated with the development of squamous cell neoplasia or conjunctival squamous cell carcinoma). [5,7,9,10] It occurs mainly in children and adults under 20 years of age. ...
... [6,7] Other types of virus have also been found: type 6 (group with low oncogenic potential-benign lesion) [8] and type 16, 18, or 45 (group with high oncogenic potential-associated with the development of squamous cell neoplasia or conjunctival squamous cell carcinoma). [5,7,9,10] It occurs mainly in children and adults under 20 years of age. This type of papilloma has a high recurrence rate. ...
Rationale:
Conjunctival papilloma is a benign neoplastic lesion of epithelial origin, with a minimal tendency toward malignancy and an exophytic growth type. Etiological factors that contribute to the appearance of papilloma are UV exposure, HPV infection, smoking, and immunodeficiency. A case report of limbal conjunctival papilloma treatment with topical interferon alpha-2b eye drops applied to the conjunctival sac.
Patient concerns:
A 49-year-old female patient treated in the Clinical Department of Ophthalmology for conjunctival lesion located in the temporal quadrant near the limbus of the right eye. Ocular examination of the patient's eye did not show any abnormalities: visual acuity-20/20, intraocular pressure-16 mmHg.
Diagnoses:
During physical examination, a broad-based pink lesion of size 4 mm × 6 mm was found in interpalpebral bulbar conjunctiva with prominent feeder vessels and soft consistency. Lesion in the biomicroscopic examination did not show any sign of malignancy. In Swept Source Optical Coherence Tomography (SS-OCT) there was no sign of infiltration into sclera or cornea. In vivo confocal microscopy (IVCM) examination, revealed loss of the normal conjunctival epithelium - hyper-reflective cells, variation of cell size. A clinical diagnosis of limbal conjunctival papilloma was made.
Interventions:
Interferon alpha-2b 1 million IU/ml eye drops were applied 4 times a day for 5 months. The treatment lasted 5 months without changing the dosing regimen. Three months after the start of the interferon treatment, a complete regression of the lesion was achieved. Treatment was continued for the following 2 months. Controlled IVCM after 6 months showed only few hyper-reflective cells and fibrotic tissue.
Outcomes:
Treatment of conjunctival papilloma with topical interferon alpha-2b led to the complete regression of the lesion. Although after the therapy the conjunctiva appears normal both in slit lamp and in the OCT examination, there is a noticeable fibrosis of the tissue in confocal microscopy. During the 14-month follow-up period, there were no recurrent lesions.
Lessons:
In this study, topical interferon alpha-2b has been shown to be an effective and safe therapy for small-to-medium-size conjunctival papilloma without any sign of malignancy.
... HPV types 6 and 11 are most frequently identified in conjunctival papillomas [2,3,15,16,18,19,21,30,31] with a reported frequency ranging from 44.4 to 75.4% and 4.71 to 28% from all lesions, respectively [15,20,31]. Types 5b, 13, 16, 20, 23, 33, and 45 have also been detected [25,[31][32][33]. ...
... Types 5b, 13, 16, 20, 23, 33, and 45 have also been detected [25,[31][32][33]. Additionally, co-infection with different papilloma virus types has been reported as in one study an individual had HPV types 6/11 and 16 identified in the conjunctival papilloma [30]. Low-risk HPV types 6 and 11 are mostly identified in children and adults with conjunctival papillomas [15], while high-risk HPV types 16 and 18 are mostly found in adults with OSSN [34,35]. ...
... This seems to be in agreement with the fact that the majority of condyloma acuminata are associated with low-risk HPV types while high-risk types are mainly associated with uterine cervical intraepithelial neoplasia and cervical cancer [29]. The mode of ocular HPV transmission is thought to vary from vertical transmission from the mother to the infant during delivery to inoculation through ocular contact with contaminated surfaces or hands [30,36,37]. Coexistent presence or history of condyloma acuminata, cutaneous and conjunctival papillomas have been reported, implying that HPV infection can simultaneously appear at multiple sites [3,13,38,39]. ...
Conjunctival papilloma is an acquired benign squamous cell tumor that can present at any age, but most frequently in the third and fourth decades of life. Papillomas have been associated with human papilloma virus (HPV) infection, usually types 6 and 11. Although histopathological diagnosis remains the gold standard, the advent of newer non-invasive imaging modalities such as optical coherence tomography (OCT) is transforming the way we diagnose and treat ocular surface tumors, including conjunctival papilloma. Management of these lesions can prove a challenge to the treating physician since not all lesions respond to medical and/or surgical therapy and in fact may worsen after surgical manipulation. In this review, the epidemiology, pathophysiology, clinical characteristics, and diagnosis of conjunctival papilloma including the use of OCT are discussed. Indications, efficacy, and side effects of currently available management options are also reviewed to guide the selection of the best treatment approach.
... Tumors of the conjunctiva and cornea occupy a large spectrum of conditions ranging from benign lesions such as limbal dermoid or myxoma to aggressive, life-threatening malignancies such as melanoma or Kaposi's sarcoma. [23,88] The clinical differentiation of these tumors is based on the patient›s medical background as well as certain typical clinical features of the tumor. The recognition and proper management of such tumors requires an understanding of the anatomy of the conjunctiva and cornea and knowledge of general principles of tumor management, both of which are described below. ...
... Squamous papilloma is a benign tumor, documented to be associated with human papillomavirus (subtypes 6, 11, 16, and 18) infection of the conjunctiva. [55,88] This tumor can occur in both children and adults. It is speculated that the virus is acquired through transfer from the mother›s vagina to the newborn›s conjunctiva as the child passes through the mother›s birth canal. ...
Tumors of the conjunctiva and cornea comprise a large and varied spectrum of conditions. These tumors are grouped into two major categories of congenital and acquired lesions. The acquired lesions are further subdivided based on origin of the mass into surface epithelial, melanocytic, vascular, fibrous, neural, histiocytic, myxoid, myogenic, lipomatous, lymphoid, leukemic, metastatic and secondary tumors. Melanocytic lesions include nevus, racial melanosis, primary acquired melanosis, melanoma, and other ocular surface conditions like ocular melanocytosis and secondary pigmentary deposition. The most frequent nonmelanocytic neoplastic lesions include squamous cell carcinoma and lymphoma, both of which have typical features appreciated on clinical examination. The caruncle displays a slightly different array of tumors compared to those elsewhere on the conjunctiva, as nevus and papilloma are most common, but oncocytoma and sebaceous gland hyperplasia, adenoma, and carcinoma can be found. In this report, we provide clinical description and illustration of the many conjunctival and corneal tumors and we discuss tumor management.
... HPV has been identified in several lesions of the ocular surface. A strong association between HPV types 6 and 11 and conjunctival papilloma has been established (49,52,57,59,60). The varied percentages of papillomas associated with HPV presence could be attributed to differences in genetic predisposition, lifestyle and environmental exposure (73). ...
Human papillomavirus (HPV) infection has been implicated as a primary cause of lesions in the anogenital region, skin, oropharynx and respiratory tract. Additionally, the role of HPV in the pathogenesis of ocular surface disease has also been extensively studied. Conjunctival papilloma development has been strongly associated with the HPV infection of certain subtypes. On the other hand, the role of HPV in conjunctival pterygium, conjunctival intraepithelial neoplasia (CIN) and ocular surface squamous neoplasia (OSSN) remains controversial. Genetic predisposition and environmental factor is important in HPV hosts as regards the pathogenesis of ocular surface disease. Several studies have indicate a synergic role of HPV with ultraviolet radiation in pterygium establishment. A higher recurrence risk rate and more aggressive disease of ophthalmic pterygium is observed in cases of HPV infection. The purpose of this review was to provide a systematic review of the literature and to assist in a better understanding of the role of HPV in ocular surface disease.
... 5 10 Low-risk human papillomavirus (LR-HPV) is associated with the occurrence of exophytic conjunctival papilloma. 11 HPV is a DNA virus with a double-stranded DNA genome, and variations in the DNA sequence define the more than 200 different genotypes, 12 typically stratified into two groups targeting either the mucosal or cutaneous tissue (International Agency for Research on Cancer [IARC] Monograph, 2012). The IARC has defined 13 HPV genotypes as carcinogenic to humans based on sufficient evidence of carcinogenicity, hereafter referred to as high-risk HPV (HR-HPV). ...
Objective
The purpose of the present study is to describe the clinical and histopathological features of conjunctival inverted papilloma, to analyse for the presence of human papillomavirus (HPV), and to determine if HPV infection is associated with this type of tumour and its inverted growth pattern.
Methods and Analysis
Cases of conjunctival inverted papillomas were retrieved from the archives of the Department of Pathology, Rigshospitalet, Denmark. Patient records and pathology reports were reviewed. Formalin-fixed and paraffin-embedded tissue was analysed for the presence of HPV by immunohistochemistry, in situ hybridisation (ISH), PCR and HPV typed by sequencing.
Results
A total of four cases were retrieved. The age at diagnosis ranged from 41 to 77 years, with an equal sex distribution. All lesions were localised to the bulbar conjunctiva and two of the cases were pigmented. Histopathological examination did not reveal areas of dysplasia. All lesions were p16-positive and p53-positive by immunohistochemistry. High-risk HPV 58 was demonstrated in one lesion by ISH and PCR.
Conclusion
Here we present four cases of conjunctival inverted papilloma, which is an exceedingly rare tumour with only 11 previously reported cases in the literature. Both clinically and histopathologically, the tumours show distinct features compared with exophytic conjunctival papillomas. Furthermore, this is the first description of high-risk HPV 58 in a conjunctival tumour. The biological behaviour of the tumour is uncertain due to its rareness. However, a complete removal of the lesion and a careful observation are recommended. The finding of HPV 58 underlines the necessity of this precaution.
