UNIVERSA MEDICINA
pISSN: 1907-3062 / eISSN: 2407-2230 Univ Med 2025.
44:328-334
DOI: https://doi.
org/10.
18051/UnivMed.
ORIGINAL ARTICLE
Retinoblastoma tumor suppressor protein is not a risk factor for the location of condyloma acuminatum among adults Pratiwi Prasetya Primisawitri1* .
Nurrachmat Mulianto1 .
Endra Yustin Ellistasari1 Eti Poncorini2 .
Harijono Kariosentono1 .
Suci Widhiati1 .
Brian Wasita3.
Novan Adi Setyawan3 , and Muhammad Yurizar Yudhistira4 Department of Dermatology and Venereology.
Faculty of Medicine.
Universitas Sebelas Maret.
Surakarta.
Indonesia Department of Public Health.
Faculty of Medicine.
Universitas Sebelas Maret.
Surakarta.
Indonesia Department of Anatomy Pathology.
Faculty of Medicine.
Universitas Sebelas Maret.
Surakarta.
Indonesia Faculty of Medicine.
Universitas Sebelas Maret.
Surakarta.
Indonesia * Correspondence Author:
prasetya@gmail.
Date of first submission.
August 8, 2025 Date of acceptance.
December 1, 2025 Date of publised.
December 3, 2025 Cite this article as: Primisawitri PP.
Mulianto N.
Ellistasari EY.
Poncorini E.
Kariosentono H.
Widhiati S, et al.
Retinoblastoma tumor suppressor protein is not a risk factor for the location of condyloma acuminatum among adults.
Univ Med 2025.
44:328334
ABSTRACT
BACKGROUND
Condylomata acuminata (CA) are sexually transmitted infections primarily caused by low-risk HPV types 6 Retinoblastoma protein .
interacts with HPV oncoproteins, leading to destabilization, genomic instability, and carcinogenesis.
This study aimed to determine whether variations in pRb expression and sexual orientation are risk factors of the anatomical location of CA lesions and to compare differences in pRb expression by sexual orientation.
METHODS
A cross-sectional study was conducted among 33 patients aged >18 years with clinically and histopathologically confirmed CA.
Demographic data, pRb expression assessed via excision biopsy and immunohistochemistry, and relevant risk factors were collected.
Statistical analyses including Simple and multiple binary logistic regression were used to analyze the data, with model fit assessed using the HosmerAeLemeshow test.
RESULTS
Weak pRb expression predominated in anal lesions .
p=0.
and among homosexual/bisexual individuals .
p=0.
, while moderate expression was more common in genital lesions .
p=0.
and heterosexual individuals .
p=0.
Simple logistic regression analysis showed that HIV status (OR=11.
p=0.
, sexual orientation (OR=13.
p=0.
, and moderate-to-strong pRb expression (OR=24.
p=0.
OR=12.
p=0.
were associated with lesion location.
In the multivariate model, pRb expression was excluded due to multicollinearity.
Sexual orientation remained the only independent predictor of lesion location (Adj OR=8.
p=0.
, with heterosexual individuals more likely to present with genital CONCLUSION The expression of pRb was not a risk factor of the anatomical location of CA, and differed between genital and anal CA.
However, sexual orientation emerged as the dominant independent factor associated with lesion Copyright@Author.
- https://univmed.
org/ejurnal/index.
php/medicina/article/view/1753 Condyloma acuminatum among adults Keywords: Condylomata acuminata.
HPV infection.
retinoblastoma protein.
sexual orientation INTRODUCTION Condylomata acuminata (CA), also known as genital warts, anal warts, or anal condylomas, are sexually transmitted infections caused by strains of the human papillomavirus (HPV), manifesting as skin-colored fleshy papules in the vulval, genital, and anal areas.
The global prevalence of CA is estimated at 10-20%.
In Bali (Indonesi.
between 2015 and 2017, the prevalence was CA affects genders differently, with genital warts affecting 72.
3% of females and 2% of males, and anal warts affecting 2.
1% and 95%, respectively.
Risk factors for HPV infection include alcohol consumption, smoking, immunodeficiency.
HIV/AIDS, uncircumcised sexual partners, a history of CA, and same-sex relationships with infrequent condom use.
Condylomata acuminata increase the risk of anogenital cancer, especially anal CA with dysplasia as a precursor to anal squamous cell The most common risk for malignancy is associated with high-risk (HR) HPV types .
, 18, 31, 33, and .
However, 90% of anogenital CA are caused by low-risk (LR) HPV types .
The retinoblastoma gene (RB.
is the first identified tumor suppressor gene, while the retinoblastoma protein .
plays a crucial role in cell cycle development.
The function of RB in cell cycle control is mediated through its interaction with the E2F family of transcription .
The human papillomavirus is associated with the destabilization of pRb-related proteins p107 and p130 by the E7 oncoprotein.
This contributes to the development of malignancy by inducing genomic instability.
Mutations in HR-HPV 16 and E7-mediated pRb immunohistochemical staining on CA.
preliminary study showed that pRb mutations could be a specific marker for HPV infection and could correlate with HPV types on CA.
Human papillomavirus infections are associated with the suppression of pRb.
It can be hypothesized that pRb expression may serve as a prognostic indicator and could correlate with HR-HPV or LR-HPV types, which are relevant for both genital and anal CA.
Detecting pRb expression in CA is considered an indicator of active HPV infection and a marker for a favorable prognosis.
Mastutik et al.
demonstrated that pRb mutation mediated by p16INK4A may serve as a specific marker for HPV infection and could correlate with HPV type.
Wei et al.
reported that the viral oncoproteins E6 and E7 inactivate several host tumor suppressor proteins, including p53, p21, and pRb, the latter often being referred to as the Auguardian of the genomeAy.
Another study observed that there was no statistically significant difference in pRb expression between cases of condylomata acuminata and cases of condylomata plana .
=0.
In contrast to previous studies that primarily immunohistochemistry without distinguishing lesion sites, the present study uniquely investigated pRb expression in condylomata acuminata across two anatomical locationsAianal and genital.
This approach provided a novel perspective on how anatomical location may influence biomarker expression patterns in HPVrelated lesions as the primary outcome.
The secondary outcome observed was the variation in pRb expression according to sexual orientation.
METHODS
Research design This study was of an analytical crosectional observational design and was conducted at the Dermatology and Venereology Clinic of Dr.
Moewardi Hospital between June and August Study subjects A total of 31 patients clinically and histopathologically diagnosed with CA were included into the study.
Inclusion criteria comprised patients aged >18 years with a diagnosis of CA, lesions located in the genital or anal region, lesion size <10 cm, and willingness to participate in the study by signing informed Exclusion criteria included patients with malignancy and autoimmune disorders.
Measurements Subjects who met the inclusion criteria were classified based on lesion location .
enital or Primisawitri PP.
Mulianto N.
Ellistasari EY, et al All participants underwent excisional biopsy under local anesthesia using 2% lidocaine HCl.
The specimens were processed for retinoblastoma protein .
expression using anti-phospho Rb (S.
antibodies, following standard deparaffinization, antigen retrieval, blocking, and staining procedures.
pRb expression was assessed using the semi-quantitative Allred scoring system, in which the final score is obtained by multiplying the staining intensity and the proportion of positively stained cells.
Staining intensity was categorized as 0 .
o stainin.
, 1 .
eak/light brow.
, 2 .
oderate/brow.
, and 3 .
trong/dark brow.
The percentage of stained cells was scored as 0 (<5%), 1 .
Ae25%), 2 .
Ae 50%), 3 .
Ae75%), and 4 (>75%).
The combined score was then grouped as follows: 0Ae1 .
, 2Ae4 .
, 5Ae8 .
, and 9Ae12 .
The measurement scale was ordinal.
Risk factor variables included gender, age, occupation, educational level, marital status, number of sexual partners, disease duration.
HIV status, and sexual orientation.
The secondary outcome was the variation in pRb expression in relation to sexual orientation.
Statistical analysis The analysis was performed using SPSS version 22 software.
A binary multiple regression analysis was used to analyze the data, with the pvalue threshold of p<0.
25 being used as a screening criterion in a simple logistic regression to select candidate variables for inclusion in the final multivariable model.
Ethical clearance The research received approval from the Ethics Committee Dr.
Moewardi Hospital/Faculty of Medicine.
Sebelas Maret University (Ethical No.
525/Vi/HREC/2.
The study adheres to the Helsinki Declaration, and all research subjects provided informed consent for medical RESULTS The study included 33 patients with CA comprising 13 with genital warts and 20 with anal Most patients were male .
7%) and the remainder female .
3%).
The majority were aged 21Ae30 years .
5%), with an age range of 17Ae63 years.
Nearly half were employed in the private sector .
5%), had completed senior high school education .
6%) and were single .
5%).
Regarding sexual orientation , the majority reported homosexual/bisexual 57.
6% and 4 % (Table .
Table 1 shows that most participants reported having less than 5 sexual partners .
2%), while 24.
2% had 6Ae10 Table 1.
Clinicopathological characteristics of the subjects .
Variables Gender Male Female Age .
21 Ae 30
31 Ae 40
Occupation Laborer Housewife Self-employed Student
Private sector
None
Educational level Elementary school
Junior high school
Senior high school
Diploma
Bachelor
Marital status
Single Married Widower Number of sexual partners 1Ae5
6 Ae 10
>10
Location of the lesion Genital only Anal only Anogenital Duration of the disease < 6 months > 6 months HIV status Non-reactive Reactive Sexual orientation Heterosexual Homosexual/Bisexual pRb expression Weak Moderate Strong Condyloma acuminatum among adults Table 2.
Comparison between pRb expression and lesion location Location of the Lesion Genital Anal Weak Moderate Strong Independent difference test: MannAeWhitney test .
rdinal dat.
*significant at p<0.
pRb expression The weak retinoblastoma protein .
expression category was predominantly found in patients with anal lesions .
3%).
Moderate pRb expression was more common among patients with genital lesions .
7%), while strong pRb expression showed an equal distribution between genital .
0%) and anal .
0%) lesion locations.
Statistical analysis revealed a significant difference in pRb expression between anal and genital lesions .
=0.
, indicating that anal lesions tended to exhibit weak pRb expression, whereas genital lesions were more likely to show moderate expression (Table .
Based on Table 3, duration (OR=1.
p=0.
was not associated with lesion location .
>0.
However.
HIV status (OR=11.
p=0.
, type of sexual relationship (OR=13.
p=0.
, moderate pRb expression (OR=24.
p=0.
, and strong pRb expression (OR=12.
p=0.
showed significant associations with lesion location.
HIV-reactive patients tended to have anal lesions, with an 11.
88-fold higher risk.
p-value Heterosexual relationships were more likely homosexual/bisexual relationships were more likely associated with anal lesions, with a 13.
33fold higher risk.
Moderate and strong pRb expressions tended to be associated with genital lesions, with 24-fold and 12-fold higher risks, respectively (Table .
Variables with p<0.
250 in the bivariate analysis were included in the multivariate analysis as follows.
In the model of Table 4, known HIV status, type of sexual relationship, and pRb expression were not significantly associated with lesion location .
>0.
This was likely due to multicollinearity among the independent variables, leading to unstable coefficient Therefore, logistic regression model 1 could not be used to predict lesion location.
In this study, the retinoblastoma protein .
expression multicollinearity, resulting in model 2 as an Table 3.
Simple logistic regression analysis of the relationship between duration.
HIV status, sexual orientation, and retinoblastoma protein .
expression with lesion location Variables Duration <6 months >6 months HIV status
Non-reactive Reactive Sexual orientation Heterosexual Homosexual/Bisexual pRb expression Weak
Moderate Strong
Site of Lesion
Genital Anal
95%CI
Lower Upper p-value Ref.
Ref.
Ref.
Ref.
Note: Chi Square/Fisher Exact test.
OR= Odd ratio.
CI= Confidence interval.
* significant p<0.
Primisawitri PP.
Mulianto N.
Ellistasari EY, et al Table 4.
Multiple logistic regression analysis of the relationship of HIV status, sexual orientation, and retinoblastoma protein .
expression with lesion location Variables Model 1
HIV
Sexual orientation pRb Expression pRb Expression.
pRb Expression.
Model 2 HIV.
Sexual Orientation .
AOR 95% C.
Lower
Upper
7E 08
1E 09
p value Note : OR= Odds Ratio.
AOR= Adjusted Odd Ratio.
CI= Confidence interval.
* significant at p<0.
The analysis showed that sexual orientation (Adj OR=8.
p=0.
was the dominant variable significantly associated with lesion location .
<0.
, where heterosexual individuals had an 8.
89-fold higher risk of genital lesions compared to homosexual/bisexual individuals.
Based on these findings, it can be concluded that sexual orientation is the dominant variable significantly associated with lesion location.
DISCUSSION
The majority of patients was aged 21Ae30 years .
5%), of male gender .
7%), and worked in the private sector .
4%).
Most had completed high school education .
6%).
Lesions were predominantly located in the anal region .
6%) compared to the genital region .
4%).
A high proportion of patients was HIV reactive .
8%), and more than half had disease durations exceeding 6 months .
5%).
Immunohistochemical analysis of pRb expression showed weak expression predominating in anal CA .
3%), whereas moderate expression was more common in genital CA .
7%).
Overall, pRb expression was undetectable in 67% of cases.
A statistically significant association was found between lesion location and pRb expression.
This study found that condylomata acuminata (CA) patients were predominantly aged 21Ae30 years, aligning with previous epidemiological reports showing peak incidence in young adults aged 18Ae30 years.
Male patients represented 31% of cases, higher than the 50% distribution reported by Puspawati et al.
This discrepancy may be attributed to differences in health-seeking behavior, anatomical factors, and spontaneous regression of lesions in females.
Lesions were most commonly located in the anal region .
6%), consistent with Rohanda et al.
who found 64% of CA cases in the anal region, particularly in men who have sex with men.
Regarding comorbidities, 81.
8% of CA patients had reactive HIV, which is substantially higher than the 2.
4Ae14% prevalence reported in high-risk .
This reflects the strong association between HIV-related immunosuppression and CA In terms of molecular findings, this study showed that weak pRb expression was dominant in anal CA .
3%) while moderate pRb expression was dominant in genital CA .
7%).
These findings are comparable to those of Soltani et al.
who reported absence of pRb expression 1% of CA cases, supporting its role as a biomarker of HPV-driven oncogenic changes.
The study highlights the association between lesion location and pRb expression status.
HPV
oncoprotein E7 binds and degrades pRb, impairing its function as a tumor suppressor.
Weak pRb expression in anal CA suggests higher oncogenic potential compared to genital CA.
Since HPV-driven carcinogenesis involves evasion of growth suppression and deregulated cell cycle progression, lesion site may be an important predictor of malignant transformation These findings provide evidence that anal CA, particularly in immunocompromised individuals, may represent a precursor state with higher malignant potential.
This study has several limitations, such as assessing pRb expression using a semiquantitative method.
More accurate quantitative methods, such as enzyme-linked immunosorbent assay (ELISA) or western blotting, are needed.
Secondly, the study did not assess low- or highrisk HPV genotypes that could affect pRb Condyloma acuminatum among adults Thirdly, the study only evaluated one type of tumor suppressor gene expression .
Assessment of other protein expressions such as p16 or p53 can be conducted to support the role of pRb as a predictor of CA turning malignant.
Fourthly, the study did not categorize HPV genotypes into HPV-HR and HPV-LR, so further research could classify HPV to identify genotypes that could predict CA turning malignant.
Immunohistochemical assessment of pRb expression may serve as a cost-effective adjunct to histopathology for identifying CA lesions with higher malignant potential, especially in the anal This could aid clinicians in stratifying patients for closer surveillance and earlier Furthermore, given the high prevalence of HIV co-infection, routine HIV screening in CA patients is crucial for integrated care and prevention of HPV-related cancers.
Further research is warranted to employ more quantitative methods for measuring pRb expression, assess the expression of additional tumor suppressor proteins .
, p16, p.
, and classify HPV genotypes to evaluate their correlation with malignant progression in condylomata acuminata (CA).
EYE.
EP.
HK, and SW.
All authors have read and approved the final manuscript.
CONCLUSION
Sexual orientation emerged as the dominant factor associated with lesion location.
The pRb expression was not a risk factor of the anatomical lesions of CA.
Overall, sexual orientation was the strongest predictor of whether lesions occurred in the genital or anal region.
Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
Data Availability Statement The data supporting the findings of this study are available from the corresponding author upon reasonable request.
Declaration of Use of AI in Scientific Writing No AI tools were used in the writing or editing of this manuscript.
REFERENCES
Conflict of Interest
No conflict of interest
Acknowledgments