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Article

Immunohistochemical Expression of Programmed Death-Ligand 1 Associated with Human Papillomavirus-Driven High-Grade Cervical Intraepithelial Neoplasia in South African Women

by
Jessica McIntyre
1,
Rahaba Marima
2,
Babatunde Alabi
2,
Gopika Ramkilawon
1 and
Benny Mosoane
1,*
1
Department of Anatomical Pathology, National Health Laboratory Services, Tshwane Academic Division, University of Pretoria, Prinshof Campus, Pretoria 0084, South Africa
2
Pan African Cancer Research Institute, University of Pretoria, Prinshof Campus, Pretoria 0084, South Africa
*
Author to whom correspondence should be addressed.
Onco 2026, 6(1), 14; https://doi.org/10.3390/onco6010014
Submission received: 9 December 2025 / Revised: 22 January 2026 / Accepted: 22 January 2026 / Published: 24 February 2026
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Simple Summary

High-grade cervical intraepithelial neoplasia is a precursor to cervical cancer and is caused by persistent infection with high-risk human papillomavirus (HPV). Immune checkpoint proteins such as programmed death-ligand 1 (PD-L1) play a role in tumour immune evasion, but their significance in pre-invasive cervical lesions is unclear. In this laboratory-based study from a South African public-sector pathology service, we assessed PD-L1 expression in HPV-driven high-grade cervical intraepithelial neoplasia using routine tissue samples. PD-L1 expression was uncommon and showed no association with lesion grade, suggesting a limited role for PD-L1 in the early stages of HPV-related cervical disease.

Abstract

Background: Cervical cancer is the second most prevalent malignancy among South African women, with high-risk human papillomavirus (HPV) infection as a critical risk factor. HPV plays a central role in cervical carcinogenesis, particularly in high-grade squamous intraepithelial lesions (HSIL). Increased programmed death ligand 1 (PD-L1) expression has been implicated in cervical carcinoma tumorigenesis. Using immunohistochemistry, this study investigated the correlation between high-risk HPV-driven cervical intraepithelial neoplasia (CIN) and PD-L1 expression. Methods: An analytical cross-sectional study was conducted on archival tissue from the Department of Anatomical Pathology, University of Pretoria (2018–2021). Formalin-fixed paraffin-embedded tissues from loop electrosurgical excisions, cone biopsies, punch biopsies, and polypectomies were analysed. PD-L1 expression was assessed using the combined proportion score (CPS). Three pathologists independently evaluated histological grade, p16 immunohistochemistry, and PD-L1 expression. Results: Among 108 cases (mean age: 37.36 years), 89.8% were CIN 3, 9.3% CIN 2, and 0.9% CIN 2–3. p16 was positive in 97.2% of cases. PD-L1 expression (CPS ≥ 1) was observed in 9.3% of cases, with a mean CPS of 1.57%. No significant association was found between PD-L1 expression and CIN grade (p = 0.6433, Cramer’s V = 0.1191) or between PD-L1 and p16 positivity (p = 1, Cramer’s V = 0.05976). Conclusions: This study demonstrates no correlation between PD-L1 expression and high-risk HPV-driven high-grade CIN. These findings suggest that immune checkpoint inhibition targeting PD-L1 may have limited therapeutic relevance in HSIL among South African women.

1. Background

Cervical cancer is a significant public health concern, ranking as the fourth most common malignancy among women globally and the second most prevalent cancer among South African women [1]. It accounts for 9.3% of cancer-related deaths in South Africa [2]. Persistent infection with high-risk human papillomavirus (HPV), particularly types 16 and 18, is the primary etiological factor in cervical cancer and its precursor lesions, with HPV DNA detected in over 95% of cases [3,4]. The risk of cervical intraepithelial neoplasia (CIN) and its progression to invasive carcinoma is exacerbated in individuals with immunosuppression, such as those infected with human immunodeficiency virus (HIV), who experience both a higher incidence and slower resolution of CIN compared to HIV-negative individuals [5]. South Africa has the largest HIV-positive population, with approximately 7.7 million infected individuals [6].
HPV is a double-stranded DNA virus comprising an 8-kilobase genome that encodes early (E1–E7) and late (L1 and L2) proteins. The oncogenic potential of HPV is largely attributed to the E6 and E7 oncoproteins, which interfere with key tumour suppressor pathways. E6 promotes the degradation of p53, inhibiting apoptosis and allowing uncontrolled cell proliferation, while E7 inactivates the retinoblastoma (Rb) protein, leading to unregulated cell cycle progression [7,8]. In high-grade squamous intraepithelial lesions (HGSIL), HPV integrates into the host genome, resulting in sustained expression of E6 and E7, loss of E2-mediated repression, and subsequent tumorigenesis [9].
The immune response plays a pivotal role in determining whether HPV infection is cleared or progresses to high-grade dysplasia and invasive carcinoma. A competent immune system can effectively eliminate HPV-infected cells, whereas immune evasion mechanisms, including the PD-1/PD-L1 checkpoint pathway, contribute to persistent infection and disease progression [10]. PD-L1 (programmed death-ligand 1), a transmembrane protein expressed on immune and tumour cells, binds to PD-1 on T-cells to suppress immune responses. This mechanism, exploited by various malignancies, enables tumours to evade immune surveillance [11]. In cervical cancer, PD-L1 expression has been linked to tumour immune evasion and may serve as a potential target for immune checkpoint inhibitors [12].
The immunohistochemical detection of PD-L1 in formalin-fixed paraffin-embedded (FFPE) tissue is essential for evaluating tumour immune microenvironments and guiding therapeutic decisions. However, variability in PD-L1 staining protocols, scoring algorithms, and interpretation criteria poses challenges in standardising assessment. Among the available scoring systems, the combined positivity score (CPS), which incorporates PD-L1 expression in both tumour and immune cells, is the preferred method for evaluating cervical carcinoma [13]. While CPS is validated for invasive disease, its relevance in high-grade CIN remains uncertain.
This study aimed to investigate the immunohistochemical expression of PD-L1 in high-risk HPV-driven CIN and assess its potential role in cervical carcinogenesis. Understanding the correlation between PD-L1 expression and HPV-related HSIL may provide insights into the immune microenvironment of precursor lesions and inform future therapeutic strategies.

2. Materials and Methods

2.1. Study Design and Sampling

This analytical cross-sectional study aimed to correlate the presence of HPV infection and PD-L1 expression in high-grade CIN. Data variables recorded included age, HPV (p16) status, and PD-L1 expression. The study was conducted in the Department of Anatomical Pathology at the University of Pretoria. Formalin-fixed paraffin-embedded (FFPE) tissue samples from female patients diagnosed with high-grade CIN were randomly selected. FFPE blocks and slides archived between 2018 and 2021 were included, with each case assigned a unique identification number to ensure patient anonymity.
The inclusion criteria required histopathologically confirmed high-grade CIN (CIN2 and CIN3) with sufficient tissue for further testing. Cases diagnosed as low-grade CIN (CIN1) and specimens with insufficient representation of the transformation zone were excluded.

2.2. Technical Procedures

Laboratory procedures were carried out in a dedicated area within the Department of Anatomical Pathology at the University of Pretoria. During specimen handling, standard personal protective equipment, including laboratory coats and gloves, was used.
The FFPE tissue blocks were placed on ice for 30–60 min to allow the wax to harden, optimising sectioning. Before sectioning, the microtome was cleaned and decontaminated using xylene and 70% ethanol. A new blade was placed on the microtome, and the block was trimmed using three sections at 20 µm intervals. For the test samples, five sections with a thickness of 4 µm were cut using a Leica 2245 microtome. Between each case, the microtome and blade were cleaned and decontaminated as necessary. The tissue sections were floated in a floatation bath and picked up on frosted slides, which were labelled with the study case number for identification. Immunohistochemical stains were performed following the sectioning process. To prevent contamination, the surface of the floatation bath was skimmed after each section. The bath was emptied at the end of each day, wiped clean, and refilled with fresh water every morning. The sections were then dried at 37 °C overnight.
P16 expression was evaluated using the CINtec® p16 Histology assay (clone E6H4™, Roche/Ventana, Tucson, AZ, USA). Immunohistochemical staining was performed on formalin-fixed, paraffin-embedded (FFPE) tissue sections using the Ventana BenchMark ULTRA automated staining system (Tucson, AZ, USA) according to the manufacturer’s instructions. The OptiView DAB IHC Detection Kit (Ventana, Tucson, AZ, USA) was used for signal detection. A strong, continuous nuclear and cytoplasmic staining pattern was considered positive, in accordance with established interpretation criteria. Appropriate positive and negative controls were included.
PD-L1 expression was assessed using the Monoclonal Mouse Anti-Human PD-L1 antibody, Clone 22C3 (Agilent/Dako, Santa Clara, CA, USA). Immunohistochemical staining was performed on FFPE tissue sections using the Dako Autostainer Link 48 (Agilent Technologies, Denmark) according to the manufacturer’s protocol. Detection was carried out using the EnVision FLEX+ system (Agilent Technologies, Glostrup, Denmark) with diaminobenzidine (DAB) as the chromogen. Appropriate positive and negative controls were also included in each run.
PD-L1 expression was assessed using the CPS, calculated as the number of PD-L1–positive tumour cells, lymphocytes, and macrophages divided by the total number of viable tumour cells, multiplied by 100. Only lesional areas were evaluated. Tumour cells were considered positive when showing partial or complete membranous staining of any intensity. Immune cells (lymphocytes and macrophages) were scored as positive when exhibiting membranous and/or cytoplasmic staining.
CPS evaluation was performed independently by three pathologists using light microscopy, and discrepant cases were reviewed jointly to reach consensus. A CPS value ≥1 was regarded as positive, in keeping with established criteria for PD-L1 assessment using the 22C3 antibody. This approach is consistent with previously published methodologies in cervical intraepithelial neoplasia and cervical squamous lesions, including the study by Brito et al. [14].
A probabilistic simple random sampling method was applied, identifying all high-grade CIN cases within the National Health Laboratory Service (NHLS) database using Systematised Nomenclature of Medicine (SNOMED) codes. The sampling frame included variables such as age, CIN grade, and HPV status. The required sample size was determined using G*Power (version 3.1.9.2). A Pearson’s chi-square test with a medium effect size (0.30), α = 0.05, power (1 − β) = 0.80, and 2 degrees of freedom indicated that a total of 108 cases were required.
A total of 108 cases diagnosed with HGSIL (CIN 2 or 3) were retrieved from the archives in the Department of Anatomical Pathology, University of Pretoria, covering the period from 1 January 2018 to 31 December 2021. All the cases included in the study had sufficient lesional tissue available for immunohistochemical staining. The sample consisted of cervical specimens, including loop electrosurgical excision procedures (LLETZ), large loop excisions of the transformation zone (LEEP), cone and punch biopsies, with one case being a polypectomy.
Haematoxylin and eosin (H&E)-stained sections from the cases were retrieved from the slide room and examined blindly by three pathologists using the nomenclature and criteria from the 5th edition of the WHO publication Classification of Tumours, Female Genital Tumours [15]. The cases were diagnosed as either CIN 2 or CIN 3, with one case exhibiting morphological features of both CIN 2 and CIN 3.
Ethical clearance for conducting this study was obtained from the University of Pretoria, reference number 2/2022 (appendix). Permission from the head of department of Anatomical Pathology, University of Pretoria/National Health Laboratory Services, to collect relevant samples was obtained. There was no direct patient involvement, with no maleficence occurring as samples were retrieved from archived diagnostic pathology specimens.

3. Results

3.1. Patient Characteristics and Histomorphology

In this study, 89.8% of HGSIL were diagnosed as CIN 3 (n = 97), characterised by full-thickness dysplasia, Figure 1A. Additionally, 9.3% (n = 10) of cases were classified as CIN 2, Figure 1B, while 0.9% (n = 1) exhibited features of both CIN 2 and CIN 3. The patient age at diagnosis ranged from 22 to 71 years, with a mean of 37.36 years (SD = ±7.93), Table 1. Age information was unavailable for one patient. HIV status was obtained from the NHLS Labtrak system, revealing that 24.8% (n = 26) of patients were HIV-positive, while the remaining 75.2% had no documented HIV results or had no status mentioned in the clinical history (Table 2). Notably, crypt involvement was observed in 90.7% (n = 98) of cases, Figure 1C, Table 2. Among these, 47.2% (n = 51) showed evidence of cervicitis, with 29.6% (n = 32) diagnosed with chronic cervicitis and 17.6% (n = 19) with follicular cervicitis, Figure 1C,D, Table 2.

3.2. P16 Immunohistochemistry

P16 immunohistochemistry performed on all 108 cases demonstrated positivity in 97.2% (n = 105), characterised by strong nuclear and cytoplasmic staining (block positivity, Figure 2A), while 2.8% (n = 3) were negative.

3.3. PD-L1 Immunohistochemistry

PD-L1 Immunohistochemistry analysis on all the cases revealed 11.1% (n = 12) positive staining for PD-L1 of varying intensity, Figure 2B–D, while 88.9% (n = 96) were negative. Among the PD-L1-positive cases, 83.3% (n = 10) had a CPS ≥ 1, while 16.7% (n = 2) scored below this threshold. Overall, PD-L1 expression was observed in 9.3% (n = 10) of cases, with the remaining 90.7% (n = 98) showing no expression. CPSs ranged from 0.02% to 4.08%, with a mean of 1.57% (SD = ±1.12%), reflecting variable expression levels among HGSIL cases, Figure 3A.

3.4. Association of PD-L1 Expression with CIN Grades and p16 Immunohistochemistry

The relationship between PD-L1 expression and CIN grade was evaluated, with all PD-L1-positive cases classified as CIN 3, as shown in Figure 3B. Fisher’s exact test yielded a p-value of 0.6433, exceeding the 10% significance threshold, indicating no statistically significant association. The Cramer’s V value of 0.1191 further supports the independence of these variables.
Similarly, the comparison between PD-L1 and p16 immunohistochemical expression showed that all PD-L1-positive cases were also positive for p16 (Figure 3C). Fisher’s exact test produced a p-value of 1, confirming no significant association. The Cramer’s V value of 0.05976 further reinforces the lack of correlation between PD-L1 and p16 expression.

4. Discussion

This study analysed 108 cases of HGSIL, encompassing CIN grades 2 and 3. The mean age at diagnosis was 37.36 years, consistent with previous South African studies [16,17,18]. The majority of cases (89.8%) were diagnosed as CIN 3, which is characterised by full-thickness epithelial dysplasia with nuclear abnormalities, loss of polarity, and frequent mitotic figures [19]. CIN 2, which accounted for 9.3% of cases, poses a diagnostic challenge due to its intermediate histological features and significant inter-observer variability. CIN 2 lesions, particularly those caused by high-risk HPV (notably HPV 16), are less likely to regress and are managed similarly to CIN 3 [20].
P16 immunohistochemistry was positive in 97.2% of cases, consistent with the literature indicating that CIN lesions typically express p16. Stoler et al. reported a 98.6% positivity rate in CIN 3 lesions, reinforcing the role of p16 as a surrogate marker for high-risk HPV infection [21,22]. This study did not include molecular HPV testing or genotyping, as it was a retrospective analysis of archived diagnostic specimens collected between 2018 and 2021, a period during which HPV DNA–based screening was not uniformly implemented in the South African public healthcare sector. Consequently, information on HPV genotypes and screening modality was not available for this cohort. These findings should therefore be interpreted within the context of routine diagnostic pathology practice in a resource-limited setting.
PD-L1 immunohistochemistry was positive in 11.1% (n = 12) of cases. Statistical analysis demonstrated no significant correlation between PD-L1 expression and CIN grade. These findings align with studies by Chinn et al. (2019) and Chang et al. (2018), both of which reported an absence of PD-L1 expression in CIN 3 [23,24]. However, other studies have found an association between PD-L1 and CIN. Mezache et al. (2015) detected PD-L1 expression in 95% of CIN 1–2 lesions [25]. Similarly, Zhang et al. (2015) reported PD-L1 positivity in 57.8% of CIN 2–3 cases, suggesting a potential role in lesion persistence or recurrence [26]. Wang et al. (2017) observed increased PD-L1 expression in CIN 2–3 compared to CIN1 and normal cervical epithelium [27]. Raghav et al. (2020) further supported this, demonstrating PD-L1 expression across 36 CIN cases [28]. The discrepancies in PD-L1 expression across studies highlight the need for a systematic review and meta-analysis to determine the strength of this association.
Both the CPS and Tumour Proportion Score (TPS) are used to assess PD-L1 expression for immunotherapy eligibility. In the KEYNOTE-158 trial, the CPS system identified more responders and is preferred for PD-L1 IHC 22C3 [29]. In this study, 83.3% (n = 10) of PD-L1-positive cases had a CPS ≥ 1, with a mean CPS of 1.57% (SD ± 1.12%).
The TPS system assesses PD-L1 expression exclusively in tumour cells and is primarily used in non-small cell lung carcinoma, with positivity defined as ≥1% and high expression as ≥50% [30]. In contrast, the CPS system evaluates PD-L1 expression in both tumour and immune cells in cervical carcinoma, head and neck squamous cell carcinoma, urothelial carcinoma, and gastro-oesophageal junction tumours, with a positivity cut-off of 1%, except for urothelial carcinoma (10%) [13,31]. The lack of a standardised PD-L1 scoring system across tumour types poses challenges for accurate interpretation [32].
All PD-L1-positive cases (n = 12) also showed p16 positivity. However, statistical analysis found no significant association between p16 and PD-L1 expression, suggesting these are independent variables. This contrasts with findings by Yang-Chun et al. (2017), who reported a correlation between PD-L1 expression and HPV infection in CIN lesions [33]. In this study, the small proportion of PD-L1-positive cases presents a challenge for drawing definitive conclusions about the relationship between PD-L1 expression and clinical features such as CIN grade, HPV type, and p16 positivity. The small sample size of PD-L1-positive cases limits the statistical power of the analysis, reducing the ability to detect significant correlations or differences. Future studies with larger sample sizes, improved statistical power, and additional analyses are needed to better understand the role of PD-L1 expression in CIN and its potential as a biomarker for prognosis or treatment response (see Supplementary Materials).
South Africa has the highest prevalence of HIV, which is known to impair immune cell function and delay CIN resolution, facilitating progression [16]. Recent studies highlight molecular interactions between HIV and HPV that amplify HPV’s oncogenic potential. HIV Tat upregulates E6 and E7 expression by increasing promoter activity, driving oncogenic transformation. HIV Vpr disrupts the G2/M checkpoint, promoting mutations in HPV-infected cells and facilitating malignant progression, underscoring the impact of HIV co-infection on HPV-driven oncogenesis [34,35]. PD-L1 overexpression plays a key role in immune evasion, an important mechanism in oncogenesis [36]. Investigating PD-L1 expression in CIN within the context of HPV and HIV co-infection may provide valuable insights into tumour immune evasion mechanisms. However, due to limited clinical data, HIV status was not assessed in this study.
HIV infection exacerbates immune dysfunction by weakening immune cell function, impairing HPV clearance, and increasing the risk of HPV-related cancers. The immunosuppressive effects of HIV, coupled with chronic HPV infection, create a tumour-promoting environment by facilitating the upregulation of immune checkpoints like PD-1/PD-L1, which suppress cytotoxic T cell activity [37,38]. HIV co-infection has been linked to impaired immune responses and worse outcomes in HPV-driven cancers, underscoring the importance of understanding immune evasion mechanisms in this context [37,39].
The PD-1/PD-L1 pathway plays a central role in immune regulation by inhibiting T cell activation. While this mechanism maintains immune homeostasis, tumour cells hijack this pathway to evade immune detection and promote tumour progression [40]. PD-1 is highly expressed on regulatory T cells (Tregs), and its signalling modulates T cell migration and metabolism through the PI3K/Akt pathway [41,42]. Tumour cells exploit the PD-1/PD-L1 axis to inhibit T cell activation, facilitating immune evasion and tumour growth [43].
In chronic viral infections like HPV, the PD-1/PD-L1 pathway also contributes to T cell exhaustion (Tex cells) [44]. These cells display impaired function, reduced cytokine production, and diminished survival, with an increased expression of inhibitory receptors like PD-1 [45,46]. HPV-related cancers, such as cervical cancer, utilise PD-L1 to activate signalling pathways (e.g., ITGB4/SNAI1/SIRT3), promoting epithelial–mesenchymal transition (EMT) and supporting tumour progression [47,48]. High PD-L1 expression in tumours can make them more susceptible to immune checkpoint inhibitors, enhancing immune responses and improving survival [48].
Furthermore, HPV infection modulates immune signalling by disrupting pathways such as NF-κB, which is involved in inflammation and immune cell recruitment [49]. HPV oncoproteins, including E6 and E7, suppress the immune response and enhance tumour progression by promoting the expression of immune checkpoints like PD-1/PD-L1. This creates an immunosuppressive microenvironment that aids in immune evasion and facilitates cancer progression [50,51].
South Africa has the highest global prevalence of HIV infection, which is known to impair immune function, delay clearance of high-risk HPV infection, and increase the risk of progression to high-grade CIN [52]. In the present study, HIV status was documented in a subset of patients (n = 26); however, due to incomplete clinical data and the limited number of HIV-positive cases, a stratified analysis of PD-L1 and p16 expression according to HIV status was not performed. Although p16 immunohistochemistry was assessed in all cases, the study was not designed or powered to evaluate potential interactions between HIV infection, PD-L1 expression, and HPV-driven CIN, highlighting the need for future studies with comprehensive clinical data and adequately powered cohorts. This study had several limitations. Clinical information was not always available, and no follow-up data were recorded, limiting further analysis. Additionally, PD-L1 expression was assessed in CIN lesions only, without comparison to invasive carcinoma. HPV status was inferred using p16 immunostaining rather than molecular confirmation. Pre-analytical variables, such as tissue fixation, sectioning, and staining, may have influenced antigen retrieval and PD-L1 immunoreactivity, potentially impacting the results.
This study was limited by its retrospective, laboratory-based design using archived FFPE tissue, which precluded access to long-term clinical follow-up and assessment of disease progression or recurrence. Consequently, the prognostic significance of p16 and PD-L1 expression could not be evaluated. Future prospective studies incorporating longitudinal clinical monitoring, HIV disease parameters, and additional immune-related biomarkers are required to better define the prognostic and biological relevance of immune checkpoint pathways in HPV-driven high-grade CIN lesions.

5. Conclusions

Finally, this study found no significant correlation between PD-L1 expression and HPV-associated high-grade cervical intraepithelial neoplasia diagnosed in South African women at our institution. P16 was widely expressed in CIN lesions, with all PD-L1-positive cases also showing p16 positivity. However, statistical analysis revealed no significant association between these markers. Findings from previous studies on PD-L1 expression in CIN remain conflicting, with some reporting minimal expression and others linking it to increasing CIN grade. This inconsistency highlights the need for further research, including systematic reviews and meta-analyses.
PD-L1 is an emerging biomarker for immunotherapy in various cancers. While this study did not establish a correlation between PD-L1 and CIN lesions, pre-analytical factors may have influenced these results. Future studies with larger cohorts, molecular HPV confirmation, and inclusion of invasive carcinoma are needed to establish PD-L1’s role in cervical neoplasia.

Supplementary Materials

The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/onco6010014/s1.

Author Contributions

Conceptualization, J.M. and B.M.; Methodology, J.M. and B.M.; Software, G.R.; Validation, B.A.; Formal analysis, G.R.; Investigation, B.M.; Data curation, J.M. and G.R.; Writing—original draft, B.M.; Writing—review & editing, R.M. and B.A.; Visualization, J.M.; Supervision, R.M.; Project administration, B.M. All authors have read and agreed to the published version of the manuscript.

Funding

This research was funded by University of Pretoria A08805, grant number AMRC SIR A1H347, NRF N1G655.

Institutional Review Board Statement

This study was approved by the Research Ethics Committee of the Faculty of Health Sciences, University of Pretoria (Ethics reference number: 2/2022, approval date: 19 January 2022).

Informed Consent Statement

Not applicable. The samples used in our study were obtained from the National Health Laboratory Services (NHLS) histology la-boratory under the University of Pretoria’s ethics approval. These samples were submitted for diagnostic purposes and carry implied consent for research use, as per institutional and NHLS policy. The research utilised archived histology material and did not involve direct interaction with patients, individual signed consent forms were not required.

Data Availability Statement

The data supporting this study’s findings are available from the corresponding author, B.M., upon reasonable request.

Conflicts of Interest

The authors declare no conflicts of interest.

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Onco 06 00014 g001
Figure 1. (A) CIN 3 showing full-thickness dysplasia of the squamous epithelium with associated endocervical crypt involvement (H&E, ×100). (B) CIN 2 showing dysplasia involving the lower two-thirds of the squamous epithelium (H&E, ×200). (C) High-grade cervical intraepithelial neoplasia with endocervical crypt involvement and background chronic cervicitis, characterised by a dense lymphoplasmacytic inflammatory infiltrate (H&E, ×200). (D) Follicular cervicitis showing a dense inflammatory infiltrate composed predominantly of lymphocytes with plasma cells, with associated lymphoid follicle formation with and without germinal centres (H&E, ×100).
Figure 1. (A) CIN 3 showing full-thickness dysplasia of the squamous epithelium with associated endocervical crypt involvement (H&E, ×100). (B) CIN 2 showing dysplasia involving the lower two-thirds of the squamous epithelium (H&E, ×200). (C) High-grade cervical intraepithelial neoplasia with endocervical crypt involvement and background chronic cervicitis, characterised by a dense lymphoplasmacytic inflammatory infiltrate (H&E, ×200). (D) Follicular cervicitis showing a dense inflammatory infiltrate composed predominantly of lymphocytes with plasma cells, with associated lymphoid follicle formation with and without germinal centres (H&E, ×100).
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Figure 2. (A) p16 immunohistochemistry showing strong, diffuse nuclear and cytoplasmic staining consistent with block-type positivity (×200). (B) PD-L1 immunohistochemistry in squamous epithelial cells showing weak staining intensity (×400). (C) PD-L1 immunohistochemistry in inflammatory cells showing cytoplasmic and membranous positivity in lymphocytes and macrophages (×400). (D) PD-L1 immunohistochemistry showing membranous positivity in squamous epithelial cells (×400).
Figure 2. (A) p16 immunohistochemistry showing strong, diffuse nuclear and cytoplasmic staining consistent with block-type positivity (×200). (B) PD-L1 immunohistochemistry in squamous epithelial cells showing weak staining intensity (×400). (C) PD-L1 immunohistochemistry in inflammatory cells showing cytoplasmic and membranous positivity in lymphocytes and macrophages (×400). (D) PD-L1 immunohistochemistry showing membranous positivity in squamous epithelial cells (×400).
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Figure 3. (A) Histogram showing the distribution of combined positive score (CPS) values in the study cohort. The x-axis represents CPS values and the y-axis represents the frequency of cases. (B) Correlation plot of PD-L1 immunohistochemistry expression according to histological diagnosis. PD-L1-positive cases were identified in CIN 3 lesions. (C) Correlation plot of PD-L1 immunohistochemistry and p16 immunohistochemical expression, showing concordant positivity in PD-L1-positive cases.
Figure 3. (A) Histogram showing the distribution of combined positive score (CPS) values in the study cohort. The x-axis represents CPS values and the y-axis represents the frequency of cases. (B) Correlation plot of PD-L1 immunohistochemistry expression according to histological diagnosis. PD-L1-positive cases were identified in CIN 3 lesions. (C) Correlation plot of PD-L1 immunohistochemistry and p16 immunohistochemical expression, showing concordant positivity in PD-L1-positive cases.
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Table 1. Age distribution of the patients.
Table 1. Age distribution of the patients.
Age in Years (n = 108)
Valid107
Missing1
Mean37.36
Median36 (33.0; 39.0)
Standard Deviation7.93
Confidence Interval (95%)37.36 (35.86; 38.87)
Minimum22
Maximum71
Table 2. Additional diagnostic information on prevalence.
Table 2. Additional diagnostic information on prevalence.
Additional Pathological and/or Clinical Information
None3 (2.8%)
Crypt involvement 98 (90.7%)
Chronic cervicitis 32 (29.6%)
Follicular cervicitis 19 (17.6%)
Endocervical polyp 1 (0.9%)
HIV26 (24.8%)
Crypt involvement with chronic cervicitis20 (18.5%)
Crypt involvement with follicular cervicitis14 (13.0%)
Crypt involvement with chronic cervicitis and HIV7 (6.5%)
Crypt involvement with follicular cervicitis and HIV3 (2.8%)
Endocervical polyp with crypt involvement with chronic cervicitis1 (0.9%)
HIV: human immunodeficiency virus.
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McIntyre, J.; Marima, R.; Alabi, B.; Ramkilawon, G.; Mosoane, B. Immunohistochemical Expression of Programmed Death-Ligand 1 Associated with Human Papillomavirus-Driven High-Grade Cervical Intraepithelial Neoplasia in South African Women. Onco 2026, 6, 14. https://doi.org/10.3390/onco6010014

AMA Style

McIntyre J, Marima R, Alabi B, Ramkilawon G, Mosoane B. Immunohistochemical Expression of Programmed Death-Ligand 1 Associated with Human Papillomavirus-Driven High-Grade Cervical Intraepithelial Neoplasia in South African Women. Onco. 2026; 6(1):14. https://doi.org/10.3390/onco6010014

Chicago/Turabian Style

McIntyre, Jessica, Rahaba Marima, Babatunde Alabi, Gopika Ramkilawon, and Benny Mosoane. 2026. "Immunohistochemical Expression of Programmed Death-Ligand 1 Associated with Human Papillomavirus-Driven High-Grade Cervical Intraepithelial Neoplasia in South African Women" Onco 6, no. 1: 14. https://doi.org/10.3390/onco6010014

APA Style

McIntyre, J., Marima, R., Alabi, B., Ramkilawon, G., & Mosoane, B. (2026). Immunohistochemical Expression of Programmed Death-Ligand 1 Associated with Human Papillomavirus-Driven High-Grade Cervical Intraepithelial Neoplasia in South African Women. Onco, 6(1), 14. https://doi.org/10.3390/onco6010014

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