Uterine cervical squamous cell carcinoma without p16 (CDKN2A) expression: Heterogeneous causes of an unusual immunophenotype

Rokutan‐Kurata, Mariyo; Minamiguchi, Sachiko; Kataoka, Tatsuki R.; Abiko, Kaoru; Mandai, Masaki; Haga, Hironori

doi:10.1111/pin.12930

Cited by 6 publications

(7 citation statements)

References 43 publications

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“…A few recent publications reported a frequency of HPVI SCCs between 0.23% and 9.09% depending on various factors, including the geographic cohort and HPV detection methods used. 3,7,[21][22][23][24][25][26][27][28][29][30][31][32][33] In the present study, only 2% of cases were HPVI, which is lower than other studies. This discrepancy may be because our cases were not geographically localized, mRNA-based HPV ISH was employed (a sensitive and specific method to detect HR-HPV, especially in combination with p16), patients treated with upfront chemoradiation were not studied (leading to enrichment of low-stage cases), and HPV-ISH-negative/ p16-positive cases were considered equivocal and excluded.…”

Section: Discussioncontrasting

confidence: 91%

“…Much less is known, however, about HPVI SCCs. A few recent publications reported a frequency of HPVI SCCs between 0.23% and 9.09% depending on various factors, including the geographic cohort and HPV detection methods used 3,7,21–33 . In the present study, only 2% of cases were HPVI, which is lower than other studies.…”

Section: Discussioncontrasting

confidence: 82%

“…In cervical SCCs, however, HPVI tumors are rare and consequently difficult to study 20–22 . Estimates of the frequency of HPVI tumors vary widely, ranging from 0.23% to 9.09% of total cases depending on the cohort studied and HPV detection methods used 3,7,21–33 . Attempts at further characterization are hampered by the low number of cases, questionable sensitivity and specificity of HPV detection methods, and frequent contamination of cohorts by ECAs, adenosquamous carcinomas, and other histologic subtypes.…”

mentioning

confidence: 99%

“…[20][21][22] Estimates of the frequency of HPVI tumors vary widely, ranging from 0.23% to 9.09% of total cases depending on the cohort studied and HPV detection methods used. 3,7,[21][22][23][24][25][26][27][28][29][30][31][32][33] Attempts at further characterization are hampered by the low number of cases, questionable sensitivity and specificity of HPV detection methods, and frequent contamination of cohorts by ECAs, adenosquamous carcinomas, and other histologic subtypes. Thus, despite its inclusion as an official entity, data regarding the frequency, clinicopathologic characteristics, and precursors to HPVI cervical SCCs are lacking.…”

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confidence: 99%

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Incidence and Clinicopathologic Characteristics of Human Papillomavirus–independent Invasive Squamous Cell Carcinomas of the Cervix

Stolnicu,

Allison,

Praiss

et al. 2023

American Journal of Surgical Pathology

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We aimed to determine the frequency of human papillomavirus–independent (HPVI) cervical squamous cell carcinoma (SCC) and to describe clinicopathologic characteristics. Among 670 patients with surgically treated SCCs in an established multi-institutional cohort, 447 had available tissue. Tissue microarrays were constructed and studied by in situ hybridization (ISH) for high-risk and low-risk human papillomavirus (HPV) mRNA and immunohistochemistry for p16 and p53. Tumors were HPVI if negative by HPV ISH and they failed to show diffuse p16 positivity by immunohistochemistry, and human papillomavirus–associated (HPVA) if positive by HPV ISH. Ten HPVI SCCs and 435 HPVA SCCs were identified; 2 cases were equivocal and excluded from analysis. The overall rate of HPVI SCC was low (2%) but was higher among older patients (7% in patients above 60 y of age and 17% in patients above 70 y of age). Compared with HPVA, patients with HPVI SCC were significantly older (median age, 72 vs. 49, P<0.001) and diagnosed at a higher stage (40% vs. 18% with stage III/IV disease, P=0.055). p53 expression was varied; 2 cases (20%) had null expression and 8 (80%) had wild-type expression. HPVI SCCs were heterogenous, with keratinizing, nonkeratinizing, and warty morphologies observed. Several cases had a precursor lesion reminiscent of differentiated vulvar intraepithelial neoplasia, with prominent basal atypia and hypereosinophilia or a basaloid-like morphology. Two patients (20%) had distant recurrences within 12 months, and 3 (30%) died of disease during follow-up. HPVI SCCs are rare tumors that are more common among older patients with higher stage disease and have important clinical and histologic differences from HPVA SCCs.

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Section: Discussioncontrasting

confidence: 91%

Section: Discussioncontrasting

confidence: 82%

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confidence: 99%

mentioning

confidence: 99%

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Incidence and Clinicopathologic Characteristics of Human Papillomavirus–independent Invasive Squamous Cell Carcinomas of the Cervix

Stolnicu,

Allison,

Praiss

et al. 2023

American Journal of Surgical Pathology

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“…Those findings are important for further studies and clinic services since P16 cytology helps avoid the atrophic changes of the cervical cells from aged women being misinterpreted as ≥HSIL by LBC. P16-immuno-stain also contributes to the indication of the invisible HSIL+ under colposcopy ( 23 ). In our study, all the LBC-≥HSIL cases that were also positive for P16 were pathologically diagnosed as ≥HSIL.…”

Section: Discussionmentioning

confidence: 99%

Performance of P16INK4a immunocytochemical stain in facilitating cytology interpretation of HSIL for HPV-positive women aged 50 and above

Hou,

Du,

Wang

et al. 2024

Front. Oncol.

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BackgroundFew articles have focused on the cytological misinterpretation of high-grade squamous intraepithelial lesion (HSIL). Due to estrogen deficiency, cervical epithelial cells in postmenopausal women tend to show atrophic change that looks like HSIL on Papanicolaou-stained cytology slides, resulting in a higher rate of cytological misinterpretation. P16INK4a immunocytochemical staining (P16 cytology) can effectively differentiate diseased cells from normal atrophic ones with less dependence on cell morphology.ObjectiveTo evaluate the role of P16 cytology in differentiating cytology HSIL from benign atrophy in women aged 50 years and above.MethodsIncluded in this analysis were women in a cervical cancer screening project conducted in central China who tested positive for high-risk human papillomavirus (hr-HPV) and returned back for triage with complete data of primary HPV testing, liquid-based cytology (LBC) analysis, P16 immuno-stained cytology interpretation, and pathology diagnosis. The included patients were grouped by age: ≥50 (1,127 cases) and <50 years (1,430 cases). The accuracy of LBC and P16 cytology in the detection of pathology ≥HSIL was compared between the two groups, and the role of P16 immuno-stain in differentiating benign cervical lesions from cytology ≥HSIL was further analyzed.ResultsOne hundred sixty-seven women (14.8%; 167/1,127) in the ≥50 group and 255 (17.8%, 255/1,430) in the <50 group were pathologically diagnosed as HSIL (Path-HSIL). LBC [≥Atypical Squamous Cell Of Undetermined Significance (ASCUS)] and P16 cytology (positive) respectively detected 63.9% (163/255) and 90.2% (230/255) of the Path-≥HSIL cases in the <50 group and 74.3% (124/167) and 93.4% (124/167) of the Path-≥HSIL cases in the ≥50 group. LBC matched with pathology in 105 (41.2%) of the 255 Path-≥HSIL cases in the <50 group and 93 (55.7%) of the 167 Path-≥HSIL cases in the ≥50 group. There were five in the <50 group and 14 in the ≥50 group that were Path-≤LSIL cases, which were interpreted by LBC as HSIL, but negative in P16 cytology.ConclusionP16 cytology facilitates differentiation of Path-≤LSIL from LBC-≥HSIL for women 50 years of age and above. It can be used in the lower-resource areas, where qualified cytologists are insufficient, as the secondary screening test for women aged ≥50 to avoid unnecessary biopsies and misinterpretation of LBC primary or secondary screening.

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Uncommon and Challenging Phenotypes of High-Risk Human Papillomavirus-Associated Head and Neck Carcinomas Revealed by High-Throughput Studies

Tannenbaum,

Lozar,

et al. 2024

Head and Neck Pathol

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Uterine cervical squamous cell carcinoma without p16 (CDKN2A) expression: Heterogeneous causes of an unusual immunophenotype

Abstract: Uterine cervical squamous cell carcinoma without p16 (CDKN2A) expression: Heterogeneous causes of an unusual immunophenotype Short running title: p16-negative uterine cervical SCC

Cited by 6 publications

References 43 publications

Incidence and Clinicopathologic Characteristics of Human Papillomavirus–independent Invasive Squamous Cell Carcinomas of the Cervix

Incidence and Clinicopathologic Characteristics of Human Papillomavirus–independent Invasive Squamous Cell Carcinomas of the Cervix

Performance of P16INK4a immunocytochemical stain in facilitating cytology interpretation of HSIL for HPV-positive women aged 50 and above

Uncommon and Challenging Phenotypes of High-Risk Human Papillomavirus-Associated Head and Neck Carcinomas Revealed by High-Throughput Studies

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