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CDK-272/ vol. 46 no. 1 th. 2019Alamat Korespondensi email: [email protected]
Human Papillomavirus Infection as the Risk Factor to Retinoblastoma
Albert Tito, Sri Yuliani Elida*
Medical Education Program, Faculty of Medicine, Tanjungpura University, *Department of Ophthalmology, Sultan Syarif Mohamad Alkadrie General Hospital, Pontianak, West Kalimantan, Indonesia
ABSTRACT
etinoblastoma b is the most common mali nant tumor o the retina in children. wo main t pes o retinoblastoma are heritable and non- heritable retinoblastoma. etinoblastoma can emer e because o loss or inactivation o b protein p b 1 ene product in chromosome 13.
in ection ma pla a role as risk actor to non-heritable retinoblastoma.
Keywords: Cancer uman apillomavirus retinoblastoma
ABSTRAK
etinoblastoma b merupakan tumor anas retina an palin umum ter adi pada anak-anak. Dua tipe retinoblastoma adalah an diturunkan dan an tidak diturunkan. etinoblastoma dapat ter adi akibat inaktivasi protein b p b an merupakan produk en 1 pada kromosom 13. In eksi mun kin berperan seba ai salah satu aktor risiko retinoblastoma. Albert Tito, Sri Yuliani lida. Infeksi Human Papillomavirus sebagai Faktor Risiko Retinoblastoma
Kata kunci: Human Papillomavirus kanker retinoblastoma
INTRODUCTION
etinoblastoma is the most common mali nant tumor o the retina in children.
he incidence is 1 in 1 000-30 000 live birth re ardless o sex race or eo raph .1 2 wo main t pes o retinoblastoma re ardin the enetic actors are heritable and non-heritable retinoblastoma. eritable retinoblastoma occurs in 40 cases.3 In heritable retinoblastoma one pair o alleles o 1 is mutated in all bod cells and urther muta enic event a ects the second allele tri errin mali nant trans ormation.
ecause o mutation in all cells a ma orit o heritable retinoblastoma develop bilateral and multi ocal tumours. In non-heritable retinoblastoma the tumour is unilateral non- transmissible and does not predispose to second non-ocular cancers.3-5 etinoblastoma can emer e because o loss or inactivation o b protein p b - 1 ene product in chromosome 13. he p b has an important role in controllin cell activation and block the potential processes to develop cancers in human includin retinoblastoma. p b binds and inactivates transcription actors such as
2 roup that re ulates cell c cle pro ression.
utation in retinoblastoma ene 1 causes loss o p b unction and leads to the increase o 2 protein release. ost retinoblastoma cases showed a mutation on its 1 17 0 non-heritable retinoblastoma cases have an intact 1 ene.3 4
Some human cancers have a viral etiolo . iral proteins such as the anti en o S 40 the 1 o adenovirus and 7 o the human papillomavirus are competent to inactivate the unction o tumor suppressor proteins.6 7 is the cause o cervical cancer and also known to be correlated to ocular lesion is seen as a papilloma d splasia and con unctival carcinoma and also can be ound in normal mucosa.5 Some research have shown the association between and retinoblastoma4 but the results are still contradictor . Studies in exican and South merican populations have reported hi h- risk t pes in 2 and 2 patients with non-heritable retinoblastoma respectivel .4 9 In contrast none o the 40 cases o non- heritable retinoblastoma showed
positive in a North merican population.10 wo studies on Indian population show 0 and 4 o associated retinoblastoma11 and a stud in Indonesia showed 16 had no role in retinoblastoma.5 nother stud in Korea showed that in ection ma have no causal relationship with retinoblastoma.12 role in retinoblastoma is still controversial.
MATERNAL TRANSMISSION OF HPV IN RETINOBLASTOMA
in ection is the main etiolo ic a ent or the development o the most cases o cervical cancer.13 in ections mi ht be spread b sexual contact.13 14 aternal transmission o mother to etus is known mi ht be occurred.13 In up to 0 o neonates born rom mother with enital have DN detectable in nasophar n eal aspirate or oral mucosa and ma persist or months or ears.13 14 stud in Korea15 showed that DN was detected at birth in 5.2 o neonates and was associated with the detection o in mothers durin an o three trimesters o pre nanc .
aternal transmissions are presumed to occur
REFERENSI:
1.PEPTIMUNE [package insert]. Jakarta, Indonesia: PT Kalbe Farma Tbk;2017.
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CDK-272/ vol. 46 no. 1 th. 2019durin the passa e o the etus throu h the in ected birth canal.13-15 DN have been detected in peripheral blood mononuclear cells o pre nant women cord blood specimens o neonates orophar n eal secretions o neonates amniotic luid etal membrane placental trophoblastic cells in ants born b elective caesarian section deliver and in s ncitiotrophoblastic cells.15-1
ased on those indin s transmission rom mother to child mi ht be a possible route o in ection to the child s e es and mi ht lead to non-heritable retinoblastoma.16-22 stud in India showed that DN were detected in neonates retinoblastoma samples and correlated to the maternal in ection b cervical brushin samples.22 aternal trans er o in retinoblastoma could be a possible route o transmission. nother stud on the association o maternal health includin sexual behavior to retinoblastoma showed a ne ative association o unilateral retinoblastoma with the use o condoms in the ear prior to pre nanc althou h this stud did not directl assess the role in retinoblastoma.23
DETECTION OF HPV TYPE ASSOCIATED WITH RETINOBLASTOMA
ased on the tissue tropism there are approximatel 200 t pes which can be divided into mucosal and cutaneous t pes. ucosal s are classi ied into low- risk and hi h-risk re ardin the mali nant pro ression o the lesions that the cause.
pproximatel 5 human cancers includin 99 cervical carcinomas penile vulvar va inal and anal carcinomas and a rowin raction o head and neck s uamous cell carcinomas are caused b hi h-risk .24 i h-risk associated cancers are enerall non-productive in ections viral proteins are produced but no viral pro en is enerated.
6 and 7 are the onl viral enes that are consistentl expressed in the cancers.6 25 Some studies showed the eo raphical distribution o DN in cervical cancer cases. he DN o 16 and 1 in nited States o merica 16 and 35 in ra il4 and 16 in India.11 In cervical cancer 16 o ten to be ound in urope while 1 is more common in sia.24 26 ut there were no enou h in ormation o t pe distribution related to retinoblastoma.27
ohan et al11 studied the detection o
DN in retinoblastoma samples in India b histopatholo indin s and pol merase chain reaction C showed that 16 was detected in 57 tumors and 1 was ne ative at all retinoblastoma samples and the p b expression was absent in 71 o retinoblastoma which had DN . alla i et al,4 also studied the presence o DN with C and dot-blot h bridi ation in samples o para in-embedded tumor tissue rom 43 children with unilateral retinoblastoma and the results showed a prevalence o DN in 27.9 o the specimens mainl 16 and 35 t pes. lida et al5 have emplo ed C in 34 retinoblastoma samples and none with 16 DN positive. oo et al12 stud did not detect in an retinoblastoma samples usin both hi h-risk or low-risk probes.
hose indin s showed the inconsistent results o DN in retinoblastoma over various studies.
PATHOGENESIS OF HPV ASSOCIATED RETINOBLASTOMA
he role o in retinoblastoma is still unknown re ardin the various contradictor results in studies around the world. ut some h potheses are proposed to describe the patho enesis o to cause retinoblastoma.25 i h-risk is important but not su icient or pro ression to cancer. he mutations in cellular enes and chromosomal rearran ements induced b enomic instabilities are the more important actors.25 27 2 6 and 7 are the primar trans ormin viral proteins and 5 enhances proli eration and ma contribute to cancer pro ression. 7 tar ets the retinoblastoma b amil o proteins that control the activit o 2 transcription actors which are re ulate in S phase enes.27 2 Inactivation o b can cause the di erentiation-dependent productive viral li ec cle and or tumor pro ression.
he disruption o b unction b 7 leads to increased levels o p53 and conse uentl the 6 proteins tar et p53 or de radation.
6 also induces telomerase expression and modulates the activities o D domain- containin proteins and tumor necrosis
actor receptors.27-30 7 proteins alter cell c cle throu h the interactions with histone deacet lases c clins and c clin-dependent kinase inhibitors. 6 and 7 cause enomic instabilit throu h multiple mechanisms includin aberrant centrosome duplication.
6 and 7 also tar et c tokine expression to
modulate cell proli eration and inter eron responses contributin to immune evasion.
5 binds to cell receptor-associated protein 31 in the endoplasmic reticulum to control tra ickin o proteins and to the vacuolar ase in endosomes to modulate epidermal rowth actor receptor turnover and maintain constitutive si nallin .27-31
ecent studies su est that p16INK4 expression in response to hi h-risk 7 expressionis the main carcino enic actor and de radation o 1 b hi h-risk 7 proteins has evolved to ne ate the p16INK4 c tostatic responses.32 ow-risk 7 proteins do not tri er p16INK4.32 33 i h-risk 7 induces p16INK4 independent o 1 inactivation throu h an epi enetic mechanism involvin the KD 6 histone demeth lase. KD 6 catal es removal o trimeth l marks on l sine 27 o histone 3 3K27me3 which are important or ene silencin b ol comb repressive complexes Cs . his is reminiscent o S onco ene-induced senescence IS a cellular de ense response involvin p16INK4 - mediated inhibition o CDK4/6 and resultin in 1 mediated cell c cle arrest and senescence.33 1 bindin and 2 activation b 7 is not su icient to thwart 1 senescence si nalin hi h-risk 7 evolved to de rade 1. i h-risk 7 proteins also activate the expression o p14 which is normall silenced b Cs. 16 7 expression causes decreased 3K27me3 marks on the p14 promoter.6 32 33 ole o in retinoblastoma could be caused b in ectious a ent exposure or other environmental actors that lead to in utero mutation. itsel is actuall not a carcino enic a ent accordin to the epidemiolo and clinical data.5 25 31 he mali nant trans ormation in an in ected cell is caused b enetic chan es.5 31 he abilit o 6 and 7 protein to do trans ormation depend on the tumor suppressor ene tumor suppressor ene protein: p53 and p b that binds to those proteins. 7 binds several cellular proteins includin p b p107 p130 and c clin . 7 and p b bindin complex causes the release o 2 1 and p b transcription actors. hese processes explain how is able to orm retinoblastoma.5 CONCLUSION
he role o in retinoblastoma is still
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CDK-272/ vol. 46 no. 1 th. 2019controversial. ased on some studies and h potheses there mi ht be a role o in ection as one o the risk actors to non-
heritable retinoblastoma althou h alone is actuall not enou h to cause carcinoma there were enetic chan es in an in ected cell
induced b in ection. Studies with lar er samples are needed.
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