Vulvar Squamous Cell Carcinoma: Comprehensive Genomic Profiling of HPV+ Versus HPV– Forms Reveals Distinct Sets of Potentially Actionable Molecular Targets Article Swipe
Erik A. Williams
,
Adrienne Werth
,
Radwa Sharaf
,
Meagan Montesion
,
Ethan S. Sokol
,
Dean C. Pavlick
,
Molly McLaughlin-Drubin
,
Rachel Erlich
,
Helen Toma
,
Kevin Jon Williams
,
J. Venstrom
,
Brian M. Alexander
,
Nikunj Shah
,
Natalie Danziger
,
Amanda Hemmerich
,
Eric A. Severson
,
Jonathan Keith Killian
,
Douglas I. Lin
,
Jeffrey S. Ross
,
Julie Y. Tse
,
Shakti Ramkissoon
,
Mark C. Mochel
,
Julia A. Elvin
·
YOU?
·
· 2020
· Open Access
·
· DOI: https://doi.org/10.1200/po.19.00406
YOU?
·
· 2020
· Open Access
·
· DOI: https://doi.org/10.1200/po.19.00406
PURPOSE Vulvar squamous cell carcinoma (vSCC) encompasses two predominant variants: one associated with detectable high-risk strains of human papillomavirus (hrHPV) and a second form often occurring in the context of chronic dermatitis in postmenopausal women. Genomic assessment of a large-scale cohort of patients with aggressive vSCC may identify distinct mutational signatures. MATERIALS AND METHODS Tumor samples from a total of 280 patients with vSCC underwent hybridization capture with analysis of up to 406 cancer-related genes. Human papillomavirus (HPV) sequences were detected by de novo assembly of nonhuman sequencing reads and aligned to the RefSeq database. Immunohistochemistry for programmed death-ligand 1 (PD-L1) was assessed. RESULTS One hundred two of 280 vSCCs (36%) contained hrHPV sequences, predominantly HPV 16 (88%). The HPV-positive (HPV+) group was significantly younger (median age, 59 v 64 years; P = .001). Compared with HPV-negative (HPV–) vSCCs, HPV+ tumors showed more frequent pathogenic alterations in PIK3CA (31% v 16%; P = .004), PTEN (14% v 2%; P < .0001), EP300 (14% v 1%; P < .0001), STK11 (14% v 1%; P < .0001), AR (5% v 0%; P = .006), and FBXW7 (10% v 3%; P = .03). In contrast, HPV– vSCCs showed more alterations in TP53 (83% v 6%; P < .0001), TERTp (71% v 9%; P < .0001), CDKN2A (55% v 2%; P < .0001), CCND1 amplification (22% v 2%; P < .0001), FAT1 (25% v 4%; P < .0001), NOTCH1 (19% v 6%; P = .002), and EGFR amplification (11% v 0%; P < .0001), as well as a higher rate of 9p24.1 ( PDL1/PDL2) amplification (5% v 1%) and PD-L1 immunohistochemistry high-positive tumor staining (33% v 9%; P = .04). CONCLUSION Comprehensive molecular profiles of vSCC vary considerably with hrHPV status and may inform patient selection into clinical trials. Sixty-one percent of HPV+ vSCCs had a pathogenic alteration in the PI3K/mTOR pathway, whereas HPV– vSCCs showed alterations in TP53, TERTp, CDKN2A, CCND1, and EGFR, and biomarkers associated with responsiveness to immunotherapy.
Related Topics
Concepts
CDKN2A
PTEN
STK11
Oncology
Internal medicine
Biology
Cancer research
Squamous intraepithelial lesion
Carcinoma
Immunohistochemistry
Medicine
Cancer
Cervical cancer
Genetics
KRAS
Cervical intraepithelial neoplasia
Colorectal cancer
PI3K/AKT/mTOR pathway
Apoptosis
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1200/po.19.00406
- https://ascopubs.org/doi/pdfdirect/10.1200/PO.19.00406
- OA Status
- bronze
- Cited By
- 48
- References
- 55
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W3034363035
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W3034363035Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1200/po.19.00406Digital Object Identifier
- Title
-
Vulvar Squamous Cell Carcinoma: Comprehensive Genomic Profiling of HPV+ Versus HPV– Forms Reveals Distinct Sets of Potentially Actionable Molecular TargetsWork title
- Type
-
articleOpenAlex work type
- Language
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enPrimary language
- Publication year
-
2020Year of publication
- Publication date
-
2020-06-16Full publication date if available
- Authors
-
Erik A. Williams, Adrienne Werth, Radwa Sharaf, Meagan Montesion, Ethan S. Sokol, Dean C. Pavlick, Molly McLaughlin-Drubin, Rachel Erlich, Helen Toma, Kevin Jon Williams, J. Venstrom, Brian M. Alexander, Nikunj Shah, Natalie Danziger, Amanda Hemmerich, Eric A. Severson, Jonathan Keith Killian, Douglas I. Lin, Jeffrey S. Ross, Julie Y. Tse, Shakti Ramkissoon, Mark C. Mochel, Julia A. ElvinList of authors in order
- Landing page
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https://doi.org/10.1200/po.19.00406Publisher landing page
- PDF URL
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https://ascopubs.org/doi/pdfdirect/10.1200/PO.19.00406Direct link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
bronzeOpen access status per OpenAlex
- OA URL
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https://ascopubs.org/doi/pdfdirect/10.1200/PO.19.00406Direct OA link when available
- Concepts
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CDKN2A, PTEN, STK11, Oncology, Internal medicine, Biology, Cancer research, Squamous intraepithelial lesion, Carcinoma, Immunohistochemistry, Medicine, Cancer, Cervical cancer, Genetics, KRAS, Cervical intraepithelial neoplasia, Colorectal cancer, PI3K/AKT/mTOR pathway, ApoptosisTop concepts (fields/topics) attached by OpenAlex
- Cited by
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48Total citation count in OpenAlex
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2025: 13, 2024: 8, 2023: 12, 2022: 5, 2021: 9Per-year citation counts (last 5 years)
- References (count)
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55Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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| counts_by_year[4].year | 2021 |
| counts_by_year[4].cited_by_count | 9 |
| counts_by_year[5].year | 2020 |
| counts_by_year[5].cited_by_count | 1 |
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| primary_location.source.host_organization | https://openalex.org/P4310315671 |
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| publication_date | 2020-06-16 |
| publication_year | 2020 |
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| abstract_inverted_index.= | 132, 152, 180, 188, 239, 274 |
| abstract_inverted_index.P | 131, 151, 158, 165, 172, 179, 187, 202, 209, 216, 224, 231, 238, 247, 273 |
| abstract_inverted_index.a | 21, 38, 57, 253, 301 |
| abstract_inverted_index.v | 128, 149, 156, 163, 170, 177, 185, 200, 207, 214, 222, 229, 236, 245, 262, 271 |
| abstract_inverted_index.16 | 116 |
| abstract_inverted_index.59 | 127 |
| abstract_inverted_index.64 | 129 |
| abstract_inverted_index.AR | 175 |
| abstract_inverted_index.In | 190 |
| abstract_inverted_index.as | 250, 252 |
| abstract_inverted_index.by | 81 |
| abstract_inverted_index.de | 82 |
| abstract_inverted_index.in | 26, 32, 146, 197, 304, 313 |
| abstract_inverted_index.of | 16, 29, 37, 41, 59, 69, 85, 107, 256, 280, 297 |
| abstract_inverted_index.to | 71, 91, 325 |
| abstract_inverted_index.up | 70 |
| abstract_inverted_index.(5% | 176, 261 |
| abstract_inverted_index.0%; | 178, 246 |
| abstract_inverted_index.1%) | 263 |
| abstract_inverted_index.1%; | 164, 171 |
| abstract_inverted_index.2%; | 157, 215, 223 |
| abstract_inverted_index.280 | 60, 108 |
| abstract_inverted_index.3%; | 186 |
| abstract_inverted_index.4%; | 230 |
| abstract_inverted_index.406 | 72 |
| abstract_inverted_index.6%; | 201, 237 |
| abstract_inverted_index.9%; | 208, 272 |
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| abstract_inverted_index.HPV | 115 |
| abstract_inverted_index.One | 104 |
| abstract_inverted_index.The | 118 |
| abstract_inverted_index.and | 20, 89, 182, 241, 264, 287, 318, 320 |
| abstract_inverted_index.for | 96 |
| abstract_inverted_index.had | 300 |
| abstract_inverted_index.may | 46, 288 |
| abstract_inverted_index.one | 10 |
| abstract_inverted_index.the | 27, 92, 305 |
| abstract_inverted_index.two | 7, 106 |
| abstract_inverted_index.was | 101, 122 |
| abstract_inverted_index.< | 159, 166, 173, 203, 210, 217, 225, 232, 248 |
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| abstract_inverted_index.(11% | 244 |
| abstract_inverted_index.(14% | 155, 162, 169 |
| abstract_inverted_index.(19% | 235 |
| abstract_inverted_index.(22% | 221 |
| abstract_inverted_index.(25% | 228 |
| abstract_inverted_index.(31% | 148 |
| abstract_inverted_index.(33% | 270 |
| abstract_inverted_index.(55% | 213 |
| abstract_inverted_index.(71% | 206 |
| abstract_inverted_index.(83% | 199 |
| abstract_inverted_index.16%; | 150 |
| abstract_inverted_index.EGFR | 242 |
| abstract_inverted_index.FAT1 | 227 |
| abstract_inverted_index.HPV+ | 139, 298 |
| abstract_inverted_index.PTEN | 154 |
| abstract_inverted_index.TP53 | 198 |
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| abstract_inverted_index.cell | 3 |
| abstract_inverted_index.form | 23 |
| abstract_inverted_index.from | 56 |
| abstract_inverted_index.into | 292 |
| abstract_inverted_index.more | 142, 195 |
| abstract_inverted_index.novo | 83 |
| abstract_inverted_index.rate | 255 |
| abstract_inverted_index.vSCC | 45, 63, 281 |
| abstract_inverted_index.vary | 282 |
| abstract_inverted_index.well | 251 |
| abstract_inverted_index.were | 79 |
| abstract_inverted_index.with | 12, 43, 62, 67, 135, 284, 323 |
| abstract_inverted_index.(36%) | 110 |
| abstract_inverted_index.(HPV) | 77 |
| abstract_inverted_index..03). | 189 |
| abstract_inverted_index..04). | 275 |
| abstract_inverted_index.CCND1 | 219 |
| abstract_inverted_index.EGFR, | 319 |
| abstract_inverted_index.EP300 | 161 |
| abstract_inverted_index.FBXW7 | 183 |
| abstract_inverted_index.Human | 75 |
| abstract_inverted_index.PD-L1 | 265 |
| abstract_inverted_index.STK11 | 168 |
| abstract_inverted_index.TERTp | 205 |
| abstract_inverted_index.TP53, | 314 |
| abstract_inverted_index.Tumor | 54 |
| abstract_inverted_index.group | 121 |
| abstract_inverted_index.hrHPV | 112, 285 |
| abstract_inverted_index.human | 17 |
| abstract_inverted_index.often | 24 |
| abstract_inverted_index.reads | 88 |
| abstract_inverted_index.total | 58 |
| abstract_inverted_index.tumor | 268 |
| abstract_inverted_index.vSCCs | 109, 193, 299, 310 |
| abstract_inverted_index.(88%). | 117 |
| abstract_inverted_index.(HPV+) | 120 |
| abstract_inverted_index.(vSCC) | 5 |
| abstract_inverted_index..001). | 133 |
| abstract_inverted_index..002), | 240 |
| abstract_inverted_index..004), | 153 |
| abstract_inverted_index..006), | 181 |
| abstract_inverted_index.9p24.1 | 257 |
| abstract_inverted_index.CCND1, | 317 |
| abstract_inverted_index.CDKN2A | 212 |
| abstract_inverted_index.HPV– | 192, 309 |
| abstract_inverted_index.NOTCH1 | 234 |
| abstract_inverted_index.PIK3CA | 147 |
| abstract_inverted_index.RefSeq | 93 |
| abstract_inverted_index.TERTp, | 315 |
| abstract_inverted_index.Vulvar | 1 |
| abstract_inverted_index.cohort | 40 |
| abstract_inverted_index.genes. | 74 |
| abstract_inverted_index.higher | 254 |
| abstract_inverted_index.inform | 289 |
| abstract_inverted_index.second | 22 |
| abstract_inverted_index.showed | 141, 194, 311 |
| abstract_inverted_index.status | 286 |
| abstract_inverted_index.tumors | 140 |
| abstract_inverted_index.vSCCs, | 138 |
| abstract_inverted_index.women. | 34 |
| abstract_inverted_index.years; | 130 |
| abstract_inverted_index.(PD-L1) | 100 |
| abstract_inverted_index.(hrHPV) | 19 |
| abstract_inverted_index.(median | 125 |
| abstract_inverted_index..0001), | 160, 167, 174, 204, 211, 218, 226, 233, 249 |
| abstract_inverted_index.CDKN2A, | 316 |
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| abstract_inverted_index.METHODS | 53 |
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| abstract_inverted_index.chronic | 30 |
| abstract_inverted_index.context | 28 |
| abstract_inverted_index.hundred | 105 |
| abstract_inverted_index.patient | 290 |
| abstract_inverted_index.percent | 296 |
| abstract_inverted_index.samples | 55 |
| abstract_inverted_index.strains | 15 |
| abstract_inverted_index.trials. | 294 |
| abstract_inverted_index.whereas | 308 |
| abstract_inverted_index.younger | 124 |
| abstract_inverted_index.(HPV–) | 137 |
| abstract_inverted_index.Compared | 134 |
| abstract_inverted_index.analysis | 68 |
| abstract_inverted_index.assembly | 84 |
| abstract_inverted_index.clinical | 293 |
| abstract_inverted_index.detected | 80 |
| abstract_inverted_index.distinct | 48 |
| abstract_inverted_index.frequent | 143 |
| abstract_inverted_index.identify | 47 |
| abstract_inverted_index.nonhuman | 86 |
| abstract_inverted_index.pathway, | 307 |
| abstract_inverted_index.patients | 42, 61 |
| abstract_inverted_index.profiles | 279 |
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| abstract_inverted_index.staining | 269 |
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| abstract_inverted_index.PI3K/mTOR | 306 |
| abstract_inverted_index.Sixty-one | 295 |
| abstract_inverted_index.assessed. | 102 |
| abstract_inverted_index.carcinoma | 4 |
| abstract_inverted_index.contained | 111 |
| abstract_inverted_index.contrast, | 191 |
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| abstract_inverted_index.high-risk | 14 |
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| abstract_inverted_index.sequences | 78 |
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| abstract_inverted_index.variants: | 9 |
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| abstract_inverted_index.alteration | 303 |
| abstract_inverted_index.assessment | 36 |
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| cited_by_percentile_year.max | 100 |
| cited_by_percentile_year.min | 89 |
| countries_distinct_count | 1 |
| institutions_distinct_count | 23 |
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