Evaluating the role of human papillomaviruses in conjunctival neoplasia

Tornesello, Maria Lina; Duraturo, Maria Luisa; Waddell, Keith; Biryahwaho, Benon; Downing, Robert; Balinandi, Stephen; Lucas, Sebastian; Buonaguro, Luigi

doi:10.1038/sj.bjc.6602921

Cited by 43 publications

(47 citation statements)

References 18 publications

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“…In fact, compared with previous studies (Ateenyi-Agaba et al, 2004;Tornesello et al, 2006;de Koning et al, 2008), we observed a higher proportion of SCCC positive for cutaneous HPV types (45%) and fewer uncharacterised cutaneous HPV types. Nevertheless, the family of cutaneous HPV types is broad and heterogeneous (IARC, 2007), so false-negative results cannot be excluded.…”

Section: Discussioncontrasting

confidence: 53%

“…Mucosal human papillomavirus (HPV) types were initially suspected to have a role in SCCC onset because of their importance in the aetiology of carcinomas of the anogenital tract and oropharynx (IARC, 2007). However, three small case -control studies from Uganda (Ateenyi-Agaba et al, 2004;Tornesello et al, 2006;de Koning et al, 2008) have suggested that cutaneous HPV types (i.e., types belonging to the genus beta and formerly referred to as Epidermodysplasia Verruciformis HPV types; IARC, 2007) are more likely candidates for the causation of SCCC than mucosal HPV types.…”

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confidence: 99%

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Human papillomavirus infection and squamous cell carcinoma of the conjunctiva

et al. 2009

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BACKGROUND: Squamous cell carcinoma of the conjunctiva (SCCC) is associated with HIV-related immunosuppression, but human papillomavirus virus (HPV) is also suspected to have a role. We carried out a case -control study to assess the role of cutaneous and mucosal HPV types in SCCC, conjunctival dysplasia, and their combination (SCCC/dysplasia) in Uganda. METHODS: We compared HPV prevalence in frozen biopsies from 94 SCCC cases (79 of whom were found to be HIV-positive), 39 dysplasia cases (34 HIV-positive), and 285 hospital controls (128 HIV-positive) having other eye conditions that required surgery. Highly sensitive PCR assays that detect 75 HPV types were used. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed, adjusting for, or stratifying by age, sex, and HIV status. RESULTS: Cutaneous HPV types were detected in 45% of SCCC cases, 41% of dysplasia cases and 11% of controls. Human papillomavirus virus 5 and 8 were the most common types in SCCC, and most often occurred in combination with other types. Associations were observed between SCCC/dysplasia and detection of both single (OR ¼ 2.3; 1.2 -4.4) and multiple (OR ¼ 18.3; 6.2 -54.4) cutaneous HPV types, and were chiefly based on findings in HIV-positive patients. Cutaneous HPV infections were rarely observed among HIV-negative patients and the association with SCCC/dysplasia was not significant (OR ¼ 2.4; 0.6 -9.6) among them. Squamous cell carcinoma of the conjunctiva/dysplasia risk and mucosal HPV types were not associated in either HIV-positive or HIV-negative patients. CONCLUSIONS: We detected cutaneous HPV types in nearly half of SCCC/dysplasia cases and often multiple types (HPV5 and 8 being most common). The role of HIV (confounder or strong enhancer of cutaneous HPV carcinogenicity) is still uncertain.

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Section: Discussioncontrasting

confidence: 53%

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confidence: 99%

Human papillomavirus infection and squamous cell carcinoma of the conjunctiva

et al. 2009

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“…Papillomaviruses are a leading candidate for causing this tumor, but current evidence for their role in this disease is contradictory. Some investigators have found an excess occurrence of cutaneous papillomavirus types in SCCCs by PCR (3,35). Others have failed to find consistent evidence of papillomavirus infection by serology (24,42) and by papillomavirus consensus PCR (Y. Chang, unpublished results) using primers HVP2/B5, CN1F/R, CP62/69, and EN1F/R (16) and GPϩb-Gp5/6 (19).…”

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confidence: 99%

Human Transcriptome Subtraction by Using Short Sequence Tags To Search for Tumor Viruses in Conjunctival Carcinoma

Feng

Taylor

Benos

et al. 2007

J Virol

102

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Digital transcript subtraction (DTS) was developed to subtract in silico known human sequences from expression library data sets, leaving candidate nonhuman sequences for further analysis. This approach requires precise discrimination between human and nonhuman cDNA sequences. Database comparisons show high likelihood that small viral sequences can be successfully distinguished from human sequences. DTS analysis of 9,026 20-bp tags from an expression library of BCBL-1 cells infected with Kaposi's sarcomaassociated herpesvirus (KSHV) resolved all but three candidate sequences. Two of these sequences belonged to KSHV transcripts, and the third belonged to an unannotated human expression sequence tag. Overall, 0.24% of transcripts from this cell line were of viral origin. DTS analysis of 241,122 expression tags from three squamous cell conjunctival carcinomas revealed that only 21 sequences did not align with sequences from human databases. All 21 candidates amplify human transcripts and have secondary evidence for being of human origin. This analysis shows that it is unlikely that distinguishable viral transcripts are present in conjunctival carcinomas at 20 transcripts per million or higher, which is the equivalent of approximately 4 transcripts per cell. DTS is a simple screening method to discover novel viral nucleic acids. It provides, for the first time, quantitative evidence against some classes of viral etiology when no viral transcripts are found, thereby reducing the uncertainty involved in new pathogen discovery.

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“…In extra genital sites, the HPV virus is involved in head and neck cancer [8], but it does not seem to be associated with conjunctival neoplasia [9], although clinical evidences suggest association with cutaneous carcinogenesis [10].…”

Section: Introductionmentioning

confidence: 99%

Human papillomavirus genital infection in modern gynecology: genetic and genomic aspects

Tinelli

Vergara²,

Leo

et al. 2007

Eur Clinics Obstet Gynaecol

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HPV (human papillomavirus) is a virus responsible for many female and male genital tract diseases. It is a small nonenveloped virus with icosahedral symmetry that contains a double-stranded DNA genomes of approximately 7,900 bp. Approximately 200 different HPVs have been characterized, classified in mucosal and cutaneous viruses, responsible for a wide spectrum of clinical conditions, from simple feet and hands warts to genital cancer. Their genome is functionally distinct in three regions. The condition of the host immune system is one of the factors that can strongly influence the natural history of HPV infection. The primary response to viral infection is cell-mediated, so conditions that compromise the immune system increase the viral infection risk. The molecular mechanisms involved in the onset of the cervical carcinoma are well defined, and they are mainly associated to the ability of the proteins E6 and E7 to neutralize the activity of p53 and retinoblastoma protein, respectively. The infection of HPV is mainly diagnosed through molecular methods. Several assays have been developed for the simultaneous identification of HPV types, the majority of which are polymerase chain reaction-based assays. Side by side with these assays, the emerging technology of the DNA chip may offer a reliable diagnostic tool for discriminating easily between many HPV genotypes.

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Evaluating the role of human papillomaviruses in conjunctival neoplasia

Cited by 43 publications

References 18 publications

Human papillomavirus infection and squamous cell carcinoma of the conjunctiva

Human papillomavirus infection and squamous cell carcinoma of the conjunctiva

Human Transcriptome Subtraction by Using Short Sequence Tags To Search for Tumor Viruses in Conjunctival Carcinoma

Human papillomavirus genital infection in modern gynecology: genetic and genomic aspects

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