Skip to main content
Top
Published in: Journal of Cancer Research and Clinical Oncology 3/2020

Open Access 01-03-2020 | Human Papillomavirus | Original Article – Cancer Research

PD-L1 expression and survival in p16-negative and -positive squamous cell carcinomas of the vulva

Authors: Bastian Czogalla, Deborah Pham, Fabian Trillsch, Miriam Rottmann, Julia Gallwas, Alexander Burges, Sven Mahner, Thomas Kirchner, Udo Jeschke, Doris Mayr, Elisa Schmoeckel

Published in: Journal of Cancer Research and Clinical Oncology | Issue 3/2020

Login to get access

Abstract

Aim

Programmed death-ligand 1 (PD-L1) has become a widely used predictive biomarker for therapy with checkpoint inhibitors in a variety of cancers. Here, we studied the expression of PD-L1 in squamous cell carcinomas of the vulva (SCCV) with regard to HPV status via its surrogate marker p16. Additionally, the status of PD-L1 and p16 were analyzed for prognostic information and potential correlation to tumor-infiltrating lymphocytes (TILs).

Methods

PD-L1 was analyzed in 128 cases of SCCV using the tumor proportion score (TPS), the immune cell score (ICS) and the combined positive score (CPS). Cases were immunostained for p16 and analyzed for stromal TILs. PD-L1, p16, and TILs were compared to clinico-pathological parameters and patient’s survival.

Results

TPS ≥ 50% and CPS ≥ 50 were correlated to a worse grading (p = 0.028 and p = 0.031), but not to FIGO-stage. CPS ≥ 50 was associated to a worse prognosis with overall survival (p = 0.021) but was not correlated to the progression-free survival. P16-positivity was correlated to a longer progression-free survival (p = 0.006) and overall survival (p = 0.023). PD-L1 expression was independent from p16 status. TILs ≥ 50% were present in 24% of the cases and were strongly correlated to PD-L1 (TPS p = 0.02, ICS p < 0.001, CPS p = 0.001).

Conclusion

Our data demonstrate that PD-L1 expression is frequent in SCCV and independent from p16 status. High PD-L1 expression was associated with an unfavorable outcome whereas p16-positivity turned out to be an independent positive prognostic factor.
Appendix
Available only for authorised users
Literature
go back to reference Abiko K, Matsumura N, Hamanishi J, Horikawa N, Murakami R, Yamaguchi K, Yoshioka Y, Baba T, Konishi I, Mandai M (2015) IFN-gamma from lymphocytes induces PD-L1 expression and promotes progression of ovarian cancer. Br J Cancer 112:1501–1509CrossRef Abiko K, Matsumura N, Hamanishi J, Horikawa N, Murakami R, Yamaguchi K, Yoshioka Y, Baba T, Konishi I, Mandai M (2015) IFN-gamma from lymphocytes induces PD-L1 expression and promotes progression of ovarian cancer. Br J Cancer 112:1501–1509CrossRef
go back to reference Badalamenti G, Fanale D, Incorvaia L, Barraco N, Listi A, Maragliano R, Vincenzi B, Calo V, Iovanna JL, Bazan V, Russo A (2018) Role of tumor-infiltrating lymphocytes in patients with solid tumors: can a drop dig a stone? Cell Immunol 343:103753CrossRef Badalamenti G, Fanale D, Incorvaia L, Barraco N, Listi A, Maragliano R, Vincenzi B, Calo V, Iovanna JL, Bazan V, Russo A (2018) Role of tumor-infiltrating lymphocytes in patients with solid tumors: can a drop dig a stone? Cell Immunol 343:103753CrossRef
go back to reference Badoual C, Hans S, Merillon N, Van Ryswick C, Ravel P, Benhamouda N, Levionnois E, Nizard M, Si-Mohamed A, Besnier N, Gey A, Rotem-Yehudar R, Pere H, Tran T, Guerin CL, Chauvat A, Dransart E, Alanio C, Albert S, Barry B, Sandoval F, Quintin-Colonna F, Bruneval P, Fridman WH, Lemoine FM, Oudard S, Johannes L, Olive D, Brasnu D, Tartour E (2013) PD-1-expressing tumor-infiltrating T cells are a favorable prognostic biomarker in HPV-associated head and neck cancer. Cancer Res 73:128–138CrossRef Badoual C, Hans S, Merillon N, Van Ryswick C, Ravel P, Benhamouda N, Levionnois E, Nizard M, Si-Mohamed A, Besnier N, Gey A, Rotem-Yehudar R, Pere H, Tran T, Guerin CL, Chauvat A, Dransart E, Alanio C, Albert S, Barry B, Sandoval F, Quintin-Colonna F, Bruneval P, Fridman WH, Lemoine FM, Oudard S, Johannes L, Olive D, Brasnu D, Tartour E (2013) PD-1-expressing tumor-infiltrating T cells are a favorable prognostic biomarker in HPV-associated head and neck cancer. Cancer Res 73:128–138CrossRef
go back to reference Choschzick M, Gut A, Fink D (2018) PD-L1 receptor expression in vulvar carcinomas is HPV-independent. Virchows Arch 473:513–516CrossRef Choschzick M, Gut A, Fink D (2018) PD-L1 receptor expression in vulvar carcinomas is HPV-independent. Virchows Arch 473:513–516CrossRef
go back to reference Del Pino M, Rodriguez-Carunchio L, Ordi J (2013) Pathways of vulvar intraepithelial neoplasia and squamous cell carcinoma. Histopathology 62:161–175CrossRef Del Pino M, Rodriguez-Carunchio L, Ordi J (2013) Pathways of vulvar intraepithelial neoplasia and squamous cell carcinoma. Histopathology 62:161–175CrossRef
go back to reference Gargano JW, Wilkinson EJ, Unger ER, Steinau M, Watson M, Huang Y, Copeland G, Cozen W, Goodman MT, Hopenhayn C, Lynch CF, Hernandez BY, Peters ES, Saber MS, Lyu CW, Sands LA, Saraiya M (2012) Prevalence of human papillomavirus types in invasive vulvar cancers and vulvar intraepithelial neoplasia 3 in the United States before vaccine introduction. J Low Genit Tract Dis 16:471–479CrossRef Gargano JW, Wilkinson EJ, Unger ER, Steinau M, Watson M, Huang Y, Copeland G, Cozen W, Goodman MT, Hopenhayn C, Lynch CF, Hernandez BY, Peters ES, Saber MS, Lyu CW, Sands LA, Saraiya M (2012) Prevalence of human papillomavirus types in invasive vulvar cancers and vulvar intraepithelial neoplasia 3 in the United States before vaccine introduction. J Low Genit Tract Dis 16:471–479CrossRef
go back to reference Hampl M, Deckers-Figiel S, Hampl JA, Rein D, Bender HG (2008) New aspects of vulvar cancer: changes in localization and age of onset. Gynecol Oncol 109:340–345CrossRef Hampl M, Deckers-Figiel S, Hampl JA, Rein D, Bender HG (2008) New aspects of vulvar cancer: changes in localization and age of onset. Gynecol Oncol 109:340–345CrossRef
go back to reference Hecking T, Thiesler T, Schiller C, Lunkenheimer JM, Ayub TH, Rohr A, Condic M, Keyver-Paik MD, Fimmers R, Kirfel J, Kuhn W, Kristiansen G, Kubler K (2017) Tumoral PD-L1 expression defines a subgroup of poor-prognosis vulvar carcinomas with non-viral etiology. Oncotarget 8:92890–92903CrossRef Hecking T, Thiesler T, Schiller C, Lunkenheimer JM, Ayub TH, Rohr A, Condic M, Keyver-Paik MD, Fimmers R, Kirfel J, Kuhn W, Kristiansen G, Kubler K (2017) Tumoral PD-L1 expression defines a subgroup of poor-prognosis vulvar carcinomas with non-viral etiology. Oncotarget 8:92890–92903CrossRef
go back to reference Hong AM, Ferguson P, Dodds T, Jones D, Li M, Yang J, Scolyer RA (2019) Significant association of PD-L1 expression with human papillomavirus positivity and its prognostic impact in oropharyngeal cancer. Oral Oncol 92:33–39CrossRef Hong AM, Ferguson P, Dodds T, Jones D, Li M, Yang J, Scolyer RA (2019) Significant association of PD-L1 expression with human papillomavirus positivity and its prognostic impact in oropharyngeal cancer. Oral Oncol 92:33–39CrossRef
go back to reference Horne ZD, Dohopolski MJ, Pradhan D, Bhargava R, Edwards RP, Kelley JL, Comerci JT, Olawaiye AB, Courtney-Brooks MB, Bockmeier MM, Berger JL, Taylor SE, Sukumvanich P, Beriwal S (2018) Human papillomavirus infection mediates response and outcome of vulvar squamous cell carcinomas treated with radiation therapy. Gynecol Oncol 151:96–101CrossRef Horne ZD, Dohopolski MJ, Pradhan D, Bhargava R, Edwards RP, Kelley JL, Comerci JT, Olawaiye AB, Courtney-Brooks MB, Bockmeier MM, Berger JL, Taylor SE, Sukumvanich P, Beriwal S (2018) Human papillomavirus infection mediates response and outcome of vulvar squamous cell carcinomas treated with radiation therapy. Gynecol Oncol 151:96–101CrossRef
go back to reference Kim HS, Lee JY, Lim SH, Park K, Sun JM, Ko YH, Baek CH, Son YI, Jeong HS, Ahn YC, Lee MY, Hong M, Ahn MJ (2016) Association between PD-L1 and HPV status and the prognostic value of PD-L1 in oropharyngeal squamous cell carcinoma. Cancer Res Treat 48:527–536CrossRef Kim HS, Lee JY, Lim SH, Park K, Sun JM, Ko YH, Baek CH, Son YI, Jeong HS, Ahn YC, Lee MY, Hong M, Ahn MJ (2016) Association between PD-L1 and HPV status and the prognostic value of PD-L1 in oropharyngeal squamous cell carcinoma. Cancer Res Treat 48:527–536CrossRef
go back to reference Lai J, Elleray R, Nordin A, Hirschowitz L, Rous B, Gildea C, Poole J (2014) Vulval cancer incidence, mortality and survival in England: age-related trends. BJOG 121:728–738CrossRef Lai J, Elleray R, Nordin A, Hirschowitz L, Rous B, Gildea C, Poole J (2014) Vulval cancer incidence, mortality and survival in England: age-related trends. BJOG 121:728–738CrossRef
go back to reference Lee LJ, Howitt B, Catalano P, Tanaka C, Murphy R, Cimbak N, DeMaria R, Bu P, Crum C, Horowitz N, Matulonis U, Viswanathan AN (2016) Prognostic importance of human papillomavirus (HPV) and p16 positivity in squamous cell carcinoma of the vulva treated with radiotherapy. Gynecol Oncol 142:293–298CrossRef Lee LJ, Howitt B, Catalano P, Tanaka C, Murphy R, Cimbak N, DeMaria R, Bu P, Crum C, Horowitz N, Matulonis U, Viswanathan AN (2016) Prognostic importance of human papillomavirus (HPV) and p16 positivity in squamous cell carcinoma of the vulva treated with radiotherapy. Gynecol Oncol 142:293–298CrossRef
go back to reference Lyford-Pike S, Peng S, Young GD, Taube JM, Westra WH, Akpeng B, Bruno TC, Richmon JD, Wang H, Bishop JA, Chen L, Drake CG, Topalian SL, Pardoll DM, Pai SI (2013) Evidence for a role of the PD-1:PD-L1 pathway in immune resistance of HPV-associated head and neck squamous cell carcinoma. Cancer Res 73:1733–1741CrossRef Lyford-Pike S, Peng S, Young GD, Taube JM, Westra WH, Akpeng B, Bruno TC, Richmon JD, Wang H, Bishop JA, Chen L, Drake CG, Topalian SL, Pardoll DM, Pai SI (2013) Evidence for a role of the PD-1:PD-L1 pathway in immune resistance of HPV-associated head and neck squamous cell carcinoma. Cancer Res 73:1733–1741CrossRef
go back to reference Ma C, Lewis J Jr (2012) Small biopsy specimens reliably indicate p16 expression status of oropharyngeal squamous cell carcinoma. Head Neck Pathol 6:208–215CrossRef Ma C, Lewis J Jr (2012) Small biopsy specimens reliably indicate p16 expression status of oropharyngeal squamous cell carcinoma. Head Neck Pathol 6:208–215CrossRef
go back to reference Meng Y, Liang H, Hu J, Liu S, Hao X, Wong MSK, Li X, Hu L (2018) PD-L1 expression correlates with tumor infiltrating lymphocytes and response to neoadjuvant chemotherapy in cervical cancer. J Cancer 9:2938–2945CrossRef Meng Y, Liang H, Hu J, Liu S, Hao X, Wong MSK, Li X, Hu L (2018) PD-L1 expression correlates with tumor infiltrating lymphocytes and response to neoadjuvant chemotherapy in cervical cancer. J Cancer 9:2938–2945CrossRef
go back to reference Mezache L, Paniccia B, Nyinawabera A, Nuovo GJ (2015) Enhanced expression of PD L1 in cervical intraepithelial neoplasia and cervical cancers. Mod Pathol 28:1594–1602CrossRef Mezache L, Paniccia B, Nyinawabera A, Nuovo GJ (2015) Enhanced expression of PD L1 in cervical intraepithelial neoplasia and cervical cancers. Mod Pathol 28:1594–1602CrossRef
go back to reference Mezache L, Magro C, Hofmeister C, Pichiorri F, Sborov D, Nuovo GJ (2017) Modulation of PD-L1 and CD8 activity in idiopathic and infectious chronic inflammatory conditions. Appl Immunohistochem Mol Morphol 25:100–109CrossRef Mezache L, Magro C, Hofmeister C, Pichiorri F, Sborov D, Nuovo GJ (2017) Modulation of PD-L1 and CD8 activity in idiopathic and infectious chronic inflammatory conditions. Appl Immunohistochem Mol Morphol 25:100–109CrossRef
go back to reference Ott PA, Bang YJ, Piha-Paul SA, Razak ARA, Bennouna J, Soria JC, Rugo HS, Cohen RB, O'Neil BH, Mehnert JM, Lopez J, Doi T, van Brummelen EMJ, Cristescu R, Yang P, Emancipator K, Stein K, Ayers M, Joe AK, Lunceford JK (2019) T-cell-inflamed gene-expression profile, programmed death ligand 1 expression, and tumor mutational burden predict efficacy in patients treated with pembrolizumab across 20 cancers: KEYNOTE-028. J Clin Oncol 37:318–327CrossRef Ott PA, Bang YJ, Piha-Paul SA, Razak ARA, Bennouna J, Soria JC, Rugo HS, Cohen RB, O'Neil BH, Mehnert JM, Lopez J, Doi T, van Brummelen EMJ, Cristescu R, Yang P, Emancipator K, Stein K, Ayers M, Joe AK, Lunceford JK (2019) T-cell-inflamed gene-expression profile, programmed death ligand 1 expression, and tumor mutational burden predict efficacy in patients treated with pembrolizumab across 20 cancers: KEYNOTE-028. J Clin Oncol 37:318–327CrossRef
go back to reference Prigge ES, Arbyn M, von Knebel Doeberitz M, Reuschenbach M (2017) Diagnostic accuracy of p16(INK4a) immunohistochemistry in oropharyngeal squamous cell carcinomas: a systematic review and meta-analysis. Int J Cancer 140:1186–1198CrossRef Prigge ES, Arbyn M, von Knebel Doeberitz M, Reuschenbach M (2017) Diagnostic accuracy of p16(INK4a) immunohistochemistry in oropharyngeal squamous cell carcinomas: a systematic review and meta-analysis. Int J Cancer 140:1186–1198CrossRef
go back to reference Riethdorf S, Neffen EF, Cviko A, Loning T, Crum CP, Riethdorf L (2004) p16INK4A expression as biomarker for HPV 16-related vulvar neoplasias. Hum Pathol 35:1477–1483CrossRef Riethdorf S, Neffen EF, Cviko A, Loning T, Crum CP, Riethdorf L (2004) p16INK4A expression as biomarker for HPV 16-related vulvar neoplasias. Hum Pathol 35:1477–1483CrossRef
go back to reference Rosenberg JE, Hoffman-Censits J, Powles T, van der Heijden MS, Balar AV, Necchi A, Dawson N, O'Donnell PH, Balmanoukian A, Loriot Y, Srinivas S, Retz MM, Grivas P, Joseph RW, Galsky MD, Fleming MT, Petrylak DP, Perez-Gracia JL, Burris HA, Castellano D, Canil C, Bellmunt J, Bajorin D, Nickles D, Bourgon R, Frampton GM, Cui N, Mariathasan S, Abidoye O, Fine GD, Dreicer R (2016) Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. Lancet 387:1909–1920CrossRef Rosenberg JE, Hoffman-Censits J, Powles T, van der Heijden MS, Balar AV, Necchi A, Dawson N, O'Donnell PH, Balmanoukian A, Loriot Y, Srinivas S, Retz MM, Grivas P, Joseph RW, Galsky MD, Fleming MT, Petrylak DP, Perez-Gracia JL, Burris HA, Castellano D, Canil C, Bellmunt J, Bajorin D, Nickles D, Bourgon R, Frampton GM, Cui N, Mariathasan S, Abidoye O, Fine GD, Dreicer R (2016) Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. Lancet 387:1909–1920CrossRef
go back to reference Ruffini E, Asioli S, Filosso PL, Lyberis P, Bruna MC, Macri L, Daniele L, Oliaro A (2009) Clinical significance of tumor-infiltrating lymphocytes in lung neoplasms. Ann Thorac Surg 87:365–371CrossRef Ruffini E, Asioli S, Filosso PL, Lyberis P, Bruna MC, Macri L, Daniele L, Oliaro A (2009) Clinical significance of tumor-infiltrating lymphocytes in lung neoplasms. Ann Thorac Surg 87:365–371CrossRef
go back to reference Salgado R, Denkert C, Demaria S, Sirtaine N, Klauschen F, Pruneri G, Wienert S, Van den Eynden G, Baehner FL, Penault-Llorca F, Perez EA, Thompson EA, Symmans WF, Richardson AL, Brock J, Criscitiello C, Bailey H, Ignatiadis M, Floris G, Sparano J, Kos Z, Nielsen T, Rimm DL, Allison KH, Reis-Filho JS, Loibl S, Sotiriou C, Viale G, Badve S, Adams S, Willard-Gallo K, Loi S, TILs Working Group International (2015) The evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer: recommendations by an International TILs Working Group 2014. Ann Oncol 26:259–271CrossRef Salgado R, Denkert C, Demaria S, Sirtaine N, Klauschen F, Pruneri G, Wienert S, Van den Eynden G, Baehner FL, Penault-Llorca F, Perez EA, Thompson EA, Symmans WF, Richardson AL, Brock J, Criscitiello C, Bailey H, Ignatiadis M, Floris G, Sparano J, Kos Z, Nielsen T, Rimm DL, Allison KH, Reis-Filho JS, Loibl S, Sotiriou C, Viale G, Badve S, Adams S, Willard-Gallo K, Loi S, TILs Working Group International (2015) The evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer: recommendations by an International TILs Working Group 2014. Ann Oncol 26:259–271CrossRef
go back to reference Sand FL, Nielsen DMB, Frederiksen MH, Rasmussen CL, Kjaer SK (2019) The prognostic value of p16 and p53 expression for survival after vulvar cancer: a systematic review and meta-analysis. Gynecol Oncol 152:208–217CrossRef Sand FL, Nielsen DMB, Frederiksen MH, Rasmussen CL, Kjaer SK (2019) The prognostic value of p16 and p53 expression for survival after vulvar cancer: a systematic review and meta-analysis. Gynecol Oncol 152:208–217CrossRef
go back to reference Scheel AH, Dietel M, Heukamp LC, Johrens K, Kirchner T, Reu S, Ruschoff J, Schildhaus HU, Schirmacher P, Tiemann M, Warth A, Weichert W, Fischer RN, Wolf J, Buettner R (2016) Harmonized PD-L1 immunohistochemistry for pulmonary squamous-cell and adenocarcinomas. Mod Pathol 29:1165–1172CrossRef Scheel AH, Dietel M, Heukamp LC, Johrens K, Kirchner T, Reu S, Ruschoff J, Schildhaus HU, Schirmacher P, Tiemann M, Warth A, Weichert W, Fischer RN, Wolf J, Buettner R (2016) Harmonized PD-L1 immunohistochemistry for pulmonary squamous-cell and adenocarcinomas. Mod Pathol 29:1165–1172CrossRef
go back to reference Schuurman MS, van den Einden LC, Massuger LF, Kiemeney LA, van der Aa MA, de Hullu JA (2013) Trends in incidence and survival of Dutch women with vulvar squamous cell carcinoma. Eur J Cancer 49:3872–3880CrossRef Schuurman MS, van den Einden LC, Massuger LF, Kiemeney LA, van der Aa MA, de Hullu JA (2013) Trends in incidence and survival of Dutch women with vulvar squamous cell carcinoma. Eur J Cancer 49:3872–3880CrossRef
go back to reference Shah W, Yan X, Jing L, Zhou Y, Chen H, Wang Y (2011) A reversed CD4/CD8 ratio of tumor-infiltrating lymphocytes and a high percentage of CD4(+)FOXP3(+) regulatory T cells are significantly associated with clinical outcome in squamous cell carcinoma of the cervix. Cell Mol Immunol 8:59–66CrossRef Shah W, Yan X, Jing L, Zhou Y, Chen H, Wang Y (2011) A reversed CD4/CD8 ratio of tumor-infiltrating lymphocytes and a high percentage of CD4(+)FOXP3(+) regulatory T cells are significantly associated with clinical outcome in squamous cell carcinoma of the cervix. Cell Mol Immunol 8:59–66CrossRef
go back to reference Shields LBE, Gordinier ME (2019) Pembrolizumab in recurrent squamous cell carcinoma of the vulva: case report and review of the literature. Gynecol Obstet Investig 84:94–98CrossRef Shields LBE, Gordinier ME (2019) Pembrolizumab in recurrent squamous cell carcinoma of the vulva: case report and review of the literature. Gynecol Obstet Investig 84:94–98CrossRef
go back to reference Siegel RL, Miller KD, Jemal A (2016) Cancer statistics, 2016. CA Cancer J Clin 66:7–30CrossRef Siegel RL, Miller KD, Jemal A (2016) Cancer statistics, 2016. CA Cancer J Clin 66:7–30CrossRef
go back to reference Sznurkowski JJ, Zawrocki A, Biernat W (2016) The overexpression of p16 is not a surrogate marker for high-risk human papilloma virus genotypes and predicts clinical outcomes for vulvar cancer. BMC Cancer 16:465CrossRef Sznurkowski JJ, Zawrocki A, Biernat W (2016) The overexpression of p16 is not a surrogate marker for high-risk human papilloma virus genotypes and predicts clinical outcomes for vulvar cancer. BMC Cancer 16:465CrossRef
go back to reference Sznurkowski JJ, Zawrocki A, Sznurkowska K, Peksa R, Biernat W (2017) PD-L1 expression on immune cells is a favorable prognostic factor for vulvar squamous cell carcinoma patients. Oncotarget 8:89903–89912PubMedPubMedCentral Sznurkowski JJ, Zawrocki A, Sznurkowska K, Peksa R, Biernat W (2017) PD-L1 expression on immune cells is a favorable prognostic factor for vulvar squamous cell carcinoma patients. Oncotarget 8:89903–89912PubMedPubMedCentral
go back to reference Tan LS, Fredrik P, Ker L, Yu FG, Wang Y, Goh BC, Loh KS, Lim CM (2016) High-risk HPV genotypes and P16INK4a expression in a cohort of head and neck squamous cell carcinoma patients in Singapore. Oncotarget 7:86730–86739PubMedPubMedCentral Tan LS, Fredrik P, Ker L, Yu FG, Wang Y, Goh BC, Loh KS, Lim CM (2016) High-risk HPV genotypes and P16INK4a expression in a cohort of head and neck squamous cell carcinoma patients in Singapore. Oncotarget 7:86730–86739PubMedPubMedCentral
go back to reference Thangarajah F, Morgenstern B, Pahmeyer C, Schiffmann LM, Puppe J, Mallmann P, Hamacher S, Buettner R, Alidousty C, Holz B, Scheel AH, Schultheis AM (2019) Clinical impact of PD-L1 and PD-1 expression in squamous cell cancer of the vulva. J Cancer Res Clin Oncol 145:1651–1660CrossRef Thangarajah F, Morgenstern B, Pahmeyer C, Schiffmann LM, Puppe J, Mallmann P, Hamacher S, Buettner R, Alidousty C, Holz B, Scheel AH, Schultheis AM (2019) Clinical impact of PD-L1 and PD-1 expression in squamous cell cancer of the vulva. J Cancer Res Clin Oncol 145:1651–1660CrossRef
go back to reference Troiano G, Caponio VCA, Zhurakivska K, Arena C, Pannone G, Mascitti M, Santarelli A, Lo Muzio L (2019) High PD-L1 expression in the tumour cells did not correlate with poor prognosis of patients suffering for oral squamous cells carcinoma: a meta-analysis of the literature. Cell Prolif 52:e12537CrossRef Troiano G, Caponio VCA, Zhurakivska K, Arena C, Pannone G, Mascitti M, Santarelli A, Lo Muzio L (2019) High PD-L1 expression in the tumour cells did not correlate with poor prognosis of patients suffering for oral squamous cells carcinoma: a meta-analysis of the literature. Cell Prolif 52:e12537CrossRef
go back to reference Wang L (2019) Prognostic effect of programmed death-ligand 1 (PD-L1) in ovarian cancer: a systematic review, meta-analysis and bioinformatics study. J Ovarian Res 12:37CrossRef Wang L (2019) Prognostic effect of programmed death-ligand 1 (PD-L1) in ovarian cancer: a systematic review, meta-analysis and bioinformatics study. J Ovarian Res 12:37CrossRef
go back to reference Wang Q, Liu F, Liu L (2017) Prognostic significance of PD-L1 in solid tumor: an updated meta-analysis. Medicine (Baltimore) 96:e6369CrossRef Wang Q, Liu F, Liu L (2017) Prognostic significance of PD-L1 in solid tumor: an updated meta-analysis. Medicine (Baltimore) 96:e6369CrossRef
go back to reference Xu X, Tan Y, Qian Y, Xue W, Wang Y, Du J, Jin L, Ding W (2019) Clinicopathologic and prognostic significance of tumor-infiltrating CD8+ T cells in patients with hepatocellular carcinoma: a meta-analysis. Medicine (Baltimore) 98:e13923CrossRef Xu X, Tan Y, Qian Y, Xue W, Wang Y, Du J, Jin L, Ding W (2019) Clinicopathologic and prognostic significance of tumor-infiltrating CD8+ T cells in patients with hepatocellular carcinoma: a meta-analysis. Medicine (Baltimore) 98:e13923CrossRef
Metadata
Title
PD-L1 expression and survival in p16-negative and -positive squamous cell carcinomas of the vulva
Authors
Bastian Czogalla
Deborah Pham
Fabian Trillsch
Miriam Rottmann
Julia Gallwas
Alexander Burges
Sven Mahner
Thomas Kirchner
Udo Jeschke
Doris Mayr
Elisa Schmoeckel
Publication date
01-03-2020
Publisher
Springer Berlin Heidelberg
Published in
Journal of Cancer Research and Clinical Oncology / Issue 3/2020
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-020-03126-9

Other articles of this Issue 3/2020

Journal of Cancer Research and Clinical Oncology 3/2020 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.