Lack of Association of High-Risk Human Papillomavirus in Ocular Surface Squamous Neoplasia in India

Manderwad, Guru Prasad; Kannabiran, Chitra; Honavar, Santosh G; Vemuganti, Geeta K.

doi:10.5858/133.8.1246

Cited by 32 publications

(6 citation statements)

References 37 publications

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“…The studies comprise a total of 1410 cases and 939 controls published between 1986 and 2019 (McDonnell et al 1986; McDonnell et al 1989; Lauer et al 1990; McDonnell et al 1992; Adachi et al 1995; Saegusa et al 1995; Waddell et al 1996; Karcioglu & Issa 1997; Nakamura et al 1997; Tabrizi et al 1997; Dushku et al 1999; Palazzi et al 2000; Toth et al 2000; Eng et al 2002; Scott et al 2002; Tulvatana et al 2003; Ateenyi‐Agaba et al 2004; Moubayed et al 2004; Jung et al 2006; Kuo et al 2006; Tornesello et al 2006; Sen et al 2007; Auw‐Haedrich et al 2008; de Koning et al 2008; Guthoff et al 2009; Manderwad et al 2009; Ateenyi‐Agaba et al 2010; Asadi‐Amoli et al 2011; Peralta et al 2011; Chauhan et al 2012; Carrilho et al 2013; Woods et al 2013; Galor et al 2015; Afrogheh et al 2016; Moyer et al 2018; Griffin et al 2019; Nagarajan et al 2019; Ramberg et al 2019; Shrestha et al 2019). All studies included in the systematic review investigated patients with a histopathological diagnosis of CIN ( n = 468 patients) or conjunctival SCC ( n = 570 patients), or unspecified as ocular surface squamous neoplasia ( n = 372).…”

Section: Resultsmentioning

confidence: 99%

“…Most studies used formalin‐fixed paraffin‐embedded (FFPE) tissue; however, fresh frozen tissue was used in five studies (Palazzi et al 2000; Ateenyi‐Agaba et al 2004; Manderwad et al 2009; Ateenyi‐Agaba et al 2010; Chauhan et al 2012). The use of polymerase chain reaction (PCR) with consensus primers of the HPV L1 open reading frame (MY09/MY11, GP5+/GP6+, PGMY09/11, L1C1/L1C2, and/or SPF1/SPF2) was the most commonly applied method for detection of viral DNA (Table 1) (Adachi et al 1995; Saegusa et al 1995; Tabrizi et al 1997; Dushku et al 1999; Palazzi et al 2000; Eng et al 2002; Tulvatana et al 2003; Jung et al 2006; Kuo et al 2006; Tornesello et al 2006; Auw‐Haedrich et al 2008; de Koning et al 2008; Manderwad et al 2009; Ateenyi‐Agaba et al 2010; Asadi‐Amoli et al 2011; Chauhan et al 2012; Carrilho et al 2013; Woods et al 2013; Afrogheh et al 2016; Griffin et al 2019; Ramberg et al 2019). Some studies applied PCR type‐specific primers or primers for detection of a limited range of genotypes only (McDonnell et al 1989; Lauer et al 1990; McDonnell et al 1992; Waddell et al 1996; Karcioglu & Issa 1997; Nakamura et al 1997; Toth et al 2000; Peralta et al 2011; Moyer et al 2018).…”

Section: Resultsmentioning

confidence: 99%

“…Some studies applied PCR type‐specific primers or primers for detection of a limited range of genotypes only (McDonnell et al 1989; Lauer et al 1990; McDonnell et al 1992; Waddell et al 1996; Karcioglu & Issa 1997; Nakamura et al 1997; Toth et al 2000; Peralta et al 2011; Moyer et al 2018). DNA in situ hybridization (Saegusa et al 1995; Nakamura et al 1997; Scott et al 2002; Moubayed et al 2004; Manderwad et al 2009; Galor et al 2015; Afrogheh et al 2016) and immunohistochemistry using HPV capsid antibodies (McDonnell et al 1986; Sen et al 2007; Guthoff et al 2009; Woods et al 2013) have also been used. The presence of HPV E6 and E7 mRNA, and thereby the presence of actively transcribing viruses, was investigated in four studies, and all four studies detected viral mRNA expression within the tumour tissue (Scott et al 2002; Griffin et al 2019; Nagarajan et al 2019; Ramberg et al 2019).…”

Section: Resultsmentioning

confidence: 99%

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Human papillomavirus infection plays a role in conjunctival squamous cell carcinoma: a systematic review and meta‐analysis of observational studies

Ramberg

Møller-Hansen

Toft

et al. 2020

Acta Ophthalmologica

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Purpose We aimed to study the prevalence of human papillomavirus (HPV) in conjunctival intraepithelial neoplasia and carcinoma. Furthermore, we aimed to explore whether geographical differences or different detection modalities are associated with the conflicting information regarding HPV and the development of the disease. Methods We searched the MEDLINE, EMBASE and Scopus databases for studies reporting on HPV and conjunctival intraepithelial neoplasia or carcinoma. The pooled prevalence proportions, odds ratio (OR) and corresponding 95% confidence intervals were calculated assuming a random‐effects model. Subgroup analyses and meta‐regression explored possible sources of heterogeneity. Results A total of 39 studies were included in the systematic review. The pooled prevalence of HPV in conjunctival intraepithelial neoplasia and carcinoma was 26%, with HPV16, 18, and 33 being the most frequently reported genotypes. Human papillomavirus (HPV) infection was associated with an increased risk of conjunctival intraepithelial neoplasia and carcinoma (OR 8.4, 95% confidence interval (CI) 3.7–19.1); lower in studies from African countries (OR 1.7, 95% CI 0.9–3.5) than other countries (OR 16.1, 95% CI 5.8–44.3), p = 0.013. Conclusion Human papillomavirus infection increases the odds of conjunctival intraepithelial neoplasia and carcinoma by 8.4 compared to healthy conjunctival mucosa or other ocular surface diseases. There seem to be geographical differences regarding HPV in conjunctival intraepithelial neoplasia and carcinoma. HPV16 was the most prevalent genotype, followed by HPV18 and HPV33, meaning that most of the HPV‐related conjunctival intraepithelial neoplasia and carcinoma may be prevented by the HPV vaccines that are currently available.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Human papillomavirus infection plays a role in conjunctival squamous cell carcinoma: a systematic review and meta‐analysis of observational studies

Ramberg

Møller-Hansen

Toft

et al. 2020

Acta Ophthalmologica

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“…Consistently, studies conducted in India and Germany showed no presence of high-risk HPV in OSSN. [13,14] The HPV prevalence in OSSN is still controversial. According to previous studies, the average prevalence of HPV in OSSN is 33.8%, with values ranging from 0 to 100%.…”

Section: Discussionmentioning

confidence: 99%

Human papilloma virus identification in ocular surface squamous neoplasia by p16 immunohistochemistry and DNA chip test

Shrestha

Choi²,

Kim

et al. 2019

Medicine

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The aim of this study was to identify the association between human papilloma virus (HPV) infection and ocular surface squamous neoplasia (OSSN) using p16 immunohistochemistry (IHC) and deoxyribonucleic acid (DNA) chip test.Thirty-eight patients who underwent surgical excision of OSSN were retrospectively studied using tissue samples. The IHC was performed to assess the expression of p16 and DNA chip test was used to detect 24 HPV serotypes.Among the 38 OSSN samples, 32 cases (84.2%) were histopathologically categorized as pre-invasive type and 6 cases (15.8%) as invasive type. The IHC for p16 showed strong positivity in 12 cases (31.6%), whereas it was negative in 26 cases (68.4%). On the other hand, only one case (2.6%) of invasive OSSN was positive for the HPV16 serotype, as assessed by DNA chip test.In OSSN, p16 expression was positive in approximately 1/3rd of the cases, whereas the majority of the 24 HPV serotypes were negative for p16. Our findings suggest that only a weak association exists between HPV infection and OSSN.

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“…With the advent of polymerase chain reaction (Mullis et al, 1986 ) and the heat‐stable Taq DNA polymerase, the presence of HPV DNA in conjunctival CIN and SCC was later shown by the same group (McDonnell et al, 1989 ). In the following years, the reported prevalence of HPV in conjunctival CIN and SCC has been substantially variable (0%–100%) (Guthoff et al, 2009 ; Kuo et al, 2006 ; Manderwad et al, 2009 ; Scott et al, 2002 ), creating uncertainty of the role of HPV in these tumors. A recent work by our group addressed this controversity by systematically evaluating the literature and performing a meta‐analysis to explore different sources of heterogeneity (Ramberg et al, 2020a ).…”

Section: Introductionmentioning

confidence: 99%

Human papillomavirus‐related neoplasia of the ocular adnexa

Ramberg

2022

Acta Ophthalmologica

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SummaryHuman papillomaviruses (HPV) are involved in approximately 5% of solid cancers worldwide. The mucosotropic genotypes infect the stratified epithelium of various locations, where persistent infection may lead to invasive carcinomas. While the causative role of HPV in certain anogenital and head and neck carcinomas is well established, the role of HPV in carcinomas arising in the mucosal membranes of the ocular adnexal tissue (the lacrimal drainage system and the conjunctiva) has been a topic of great uncertainty. Therefore, we conducted a series of studies to assess the correlation between HPV and carcinomas arising in the mucosa of the ocular adnexal tissue and characterize the clinical, histopathological, and genomic features of the tumors in the context of HPV status in a Danish nationwide cohort.We collected clinical and histopathological data and tumor specimens from patients with carcinomas of the conjunctiva and the lacrimal drainage system, and their potential precursors, identified in Danish nationwide registries. The HPV status of the tumors was determined by the combined use of HPV DNA polymerase chain reaction (PCR), HPV E6/E7 mRNA in‐situ hybridization, and p16 immunohistochemistry. The genomic profile was investigated by high‐throughput DNA sequencing targeting 523 cancer‐relevant genes. The literature to date on carcinomas of the lacrimal drainage system and the conjunctiva was summarized.In the Danish cohort, 67% of all carcinomas of the lacrimal drainage system and 21% of all conjunctival carcinomas were HPV‐positive. HPV16 was the most frequently implicated genotype. A full‐thickness expression of the viral oncogenes E6 and E7 was evident in almost all HPV DNA‐positive cases. The HPV‐positive carcinomas of the conjunctiva and the lacrimal drainage system shared histopathological and genomic features distinct from their HPV‐negative counterparts. The HPV‐positive carcinomas were characterized by a non‐keratinizing morphology, p16 overexpression, high transcriptional activity of HPV E6/E7, and frequent pathogenic variants in the PI3K‐AKT signaling cascade. In contrast, the HPV‐negative carcinomas were characterized by a keratinizing morphology, lack of p16 and E6/E7 expression, and frequent somatic pathogenic variants in TP53, CDKN2A, and RB1. Among the patients with conjunctival tumors, HPV positivity was associated with a younger age at diagnosis and a higher risk of recurrence.In conclusion, the results support an etiological role of HPV in a subset of conjunctival and LDS carcinomas and their precursor lesions. Our investigations have shown that the HPV‐positive carcinomas of the ocular adnexa share genomic and phenotypic characteristics with HPV‐positive carcinomas of other anatomical locations. Therefore, these patients may be eligible for inclusion in future basket trials and future treatment regimens tailored to the more frequently occurring HPV‐positive carcinomas of other locations. Future research will further elucidate the diagnostic, prognostic, and predictive role of HPV in these carcinomas.

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Lack of Association of High-Risk Human Papillomavirus in Ocular Surface Squamous Neoplasia in India

Cited by 32 publications

References 37 publications

Human papillomavirus infection plays a role in conjunctival squamous cell carcinoma: a systematic review and meta‐analysis of observational studies

Human papillomavirus infection plays a role in conjunctival squamous cell carcinoma: a systematic review and meta‐analysis of observational studies

Human papilloma virus identification in ocular surface squamous neoplasia by p16 immunohistochemistry and DNA chip test

Human papillomavirus‐related neoplasia of the ocular adnexa

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