WHO-Klassifikation 2020 für Tumoren des unteren weiblichen Genitales

Zusammenfassung

In der WHO-Klassifikation 2020 steht die Unterscheidung von HPV-assoziierten und HPV-unabhängigen Plattenepithelkarzinomen des unteren weiblichen Genitales im Vordergrund. Die Unterscheidung der HPV-Assoziation ersetzt das Grading nicht, für welches jedoch kein Gradingsystem empfohlen wird. Auch bei der VIN erfolgt die Trennung nach HPV-(p16-)Assoziation. HPV-unabhängige Adenokarzinome (AC) der Cervix uteri sind prognostisch ungünstiger. Als Surrogatmarker für eine HPV-Assoziation gilt der immunhistochemische Nachweis von p16. Beim HPV-assoziierten AC der Cervix uteri erfolgt die prognostisch relevante Angabe des sog. Silva-Patterns.

Schlüsselwörter

p16-Immunhistochemie - HPV - Silva Pattern

• References/Literatur

• 1 Lokuhetty D, White VA, Watanabe R. Female genital Tumours. 5th ed. Lyon: Internal Agency for Research on Cancer (IARC); 2020
• 2 Singh N, Gilks CB. Vulval squamous cell carcinoma and its precursors. Histopathology 2020; 76: 128-138
• 3 Watkins JC. Human Papillomavirus-Independent Squamous Lesions of the Vulva. Surg Pathol Clin 2019; 12: 249-261
• 4 Heller DS, Day T, Allbritton JI. et al. Diagnostic Criteria for Differentiated Vulvar Intraepithelial Neoplasia and Vulvar Aberrant Maturation. J Low Genit Tract Dis 2021; 25: 57-70
• 5 Barlow EL, Lambie N, Donoghoe MW. et al. The Clinical Relevance of p16 and p53 Status in Patients with Squamous Cell Carcinoma of the Vulva. J Oncol 2020; 2020: 3739075
• 6 Sand FL, Nielsen DMB, Frederiksen MH. et al. The prognostic value of p16 and p53 expression for survival after vulvar cancer: A systematic review and meta-analysis. Gynecol Oncol 2019; 152: 208-217
• 7 Tessier-Cloutier B, Pors J, Thompson E. et al. Molecular characterization of invasive and in situ squamous neoplasia of the vulva and implications for morphologic diagnosis and outcome. Mod Pathol 2021; 34: 508-518
• 8 Cheng AS, Karnezis AN, Jordan S. et al. p16 Immunostaining Allows for Accurate Subclassification of Vulvar Squamous Cell Carcinoma Into HPV-Associated and HPV-Independent Cases. Int J Gynecol Pathol 2016; 35: 385-393
• 9 Santos M, Landolfi S, Olivella A. et al. p16 overexpression identifies HPV-positive vulvar squamous cell carcinomas. Am J Surg Pathol 2006; 30: 1347-1356
• 10 Nooij LS, Ter Haar NT, Ruano D. et al. Genomic Characterization of Vulvar (Pre)cancers Identifies Distinct Molecular Subtypes with Prognostic Significance. Clin Cancer Res 2017; 23: 6781-6789
• 11 Woelber L, Prieske K, Eulenburg C. et al. p53 and p16 expression profiles in vulvar cancer: a translational analysis by the Arbeitsgemeinschaft Gynäkologische Onkologie Chemo and Radiotherapy in Epithelial Vulvar Cancer study group. Am J Obstet Gynecol 2021; 224: 595.e1-595.e11
• 12 Darragh TM, Colgan TJ, Thomas Cox J. et al. The Lower Anogenital Squamous Terminology Standardization project for HPV-associated lesions: background and consensus recommendations from the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology. Int J Gynecol Pathol 2013; 32: 76-115
• 13 Dasgupta S, Ewing-Graham PC, Swagemakers SMA. et al. Precursor lesions of vulvar squamous cell carcinoma – histology and biomarkers: A systematic review. Crit Rev Oncol Hematol 2020; 147: 102866
• 14 Tessier-Cloutier B, Kortekaas KE, Thompson E. et al. Major p53 immunohistochemical patterns in in situ and invasive squamous cell carcinomas of the vulva and correlation with TP53 mutation status. Mod Pathol 2020; 33: 1595-1605
• 15 Yap ML, Allo G, Cuartero J. et al. Prognostic Significance of Human Papilloma Virus and p16 Expression in Patients with Vulvar Squamous Cell Carcinoma who Received Radiotherapy. Clin Oncol (R Coll Radiol) 2018; 30: 254-261
• 16 Lee LJ, Howitt B, Catalano P. et al. Prognostic importance of human papillomavirus (HPV) and p16 positivity in squamous cell carcinoma of the vulva treated with radiotherapy. Gynecol Oncol 2016; 142: 293-298
• 17 Proctor L, Hoang L, Moore J. et al. Association of human papilloma virus status and response to radiotherapy in vulvar squamous cell carcinoma. Int J Gynecol Cancer 2020; 30: 100-106
• 18 Allo G, Yap ML, Cuartero J. et al. HPV-independent Vulvar Squamous Cell Carcinoma is Associated With Significantly Worse Prognosis Compared With HPV-associated Tumors. Int J Gynecol Pathol 2020; 39: 391-399
• 19 Rasmussen CL, Sand FL, Hoffmann Frederiksen M. et al. Does HPV status influence survival after vulvar cancer?. Int J Cancer 2018; 142: 1158-1165
• 20 McAlpine JN, Leung SCY, Cheng A. et al. Human papillomavirus (HPV)-independent vulvar squamous cell carcinoma has a worse prognosis than HPV-associated disease: a retrospective cohort study. Histopathology 2017; 71: 238-246
• 21 Angelico G, Santoro A, Inzani F. et al. Hormonal Environment and HER2 Status in Extra-Mammary Pagetʼs Disease (eMPD): A Systematic Literature Review and Meta-Analysis with Clinical Considerations. Diagnostics (Basel) 2020; 10: 1040
• 22 Hellman K, Lindquist D, Ranhem C. et al. Human papillomavirus, p16(INK4A), and Ki-67 in relation to clinicopathological variables and survival in primary carcinoma of the vagina. Br J Cancer 2014; 110: 1561-1570
• 23 Höckel M, Horn L-C, Illig R. et al. Ontogenetic anatomy of the distal vagina: relevance for local tumor spread and implications for cancer surgery. Gynecol Oncol 2011; 122: 313-318
• 24 Horn L-C, Höhn AK, Hampl M. et al. S2k-Leitlinie Diagnostik und Therapie des Vaginalkarzinoms und seiner Vorstufen – Anforderungen an die Pathologie. Der Pathologe 2021; 42: 116-124
• 25 de Sanjosé S, Serrano B, Tous S. et al. RIS HPV TT, VVAP and Head and Neck study groups. Burden of Human Papillomavirus (HPV)-Related Cancers Attributable to HPVs 6/11/16/18/31/33/45/52 and 58. JNCI Cancer Spectr 2019; 2: pky045
• 26 Li N, Franceschi S, Howell-Jones R. et al. Human papillomavirus type distribution in 30,848 invasive cervical cancers worldwide: Variation by geographical region, histological type and year of publication. Int J Cancer 2011; 128: 927-935
• 27 Casey S, Harley I, Jamison J. et al. A rare case of HPV-negative cervical squamous cell carcinoma. Int J Gynecol Pathol 2015; 34: 208-212
• 28 Hodgson A, Olkhov-Mitsel E, Howitt BE. et al. International Endocervical Adenocarcinoma Criteria and Classification (IECC): correlation with adverse clinicopathological features and patient outcome. J Clin Pathol 2019; 72: 347-353
• 29 Stolnicu S, Hoang L, Chiu D. et al. Clinical Outcomes of HPV-associated and Unassociated Endocervical Adenocarcinomas Categorized by the International Endocervical Adenocarcinoma Criteria and Classification (IECC). Am J Surg Pathol 2019; 43: 466-474
• 30 Nicolás I, Saco A, Barnadas E. et al. Prognostic implications of genotyping and p16 immunostaining in HPV-positive tumors of the uterine cervix. Mod Pathol 2020; 33: 128-137
• 31 Stolnicu S, Barsan I, Hoang L. et al. International Endocervical Adenocarcinoma Criteria and Classification (IECC): A New Pathogenetic Classification for Invasive Adenocarcinomas of the Endocervix. Am J Surg Pathol 2018; 42: 214-226
• 32 AWMF. S3-Leitlinie zur Diagnostik, Therapie und Nachsorge der Patientin mit Zervixkarzinom, 2021. Accessed January 26, 2021 at: https://www.awmf.org/leitlinien/detail/ll/032-033OL.html
• 33 Nuovo GJ, Plaia TW, Belinsky SA. et al. In situ detection of the hypermethylation-induced inactivation of the p16 gene as an early event in oncogenesis. Proc Natl Acad Sci U S A 1999; 96: 12754-12759
• 34 Shain AF, Kwok S, Folkins AK. et al. Utility of p16 Immunohistochemistry in Evaluating Negative Cervical Biopsies Following High-risk Pap Test Results. Am J Surg Pathol 2018; 42: 69-75
• 35 Shain AF, Wilbur DC, Stoler MH. et al. Test Characteristics of Specific p16 Clones in the Detection of High-grade Squamous Intraepithelial Lesions (HSIL). Int J Gynecol Pathol 2018; 37: 82-87
• 36 Nuovo AJ, Garofalo M, Mikhail A. et al. The effect of aging of formalin-fixed paraffin-embedded tissues on the in situ hybridization and immunohistochemistry signals in cervical lesions. Diagn Mol Pathol 2013; 22: 164-173
• 37 Carleton C, Hoang L, Sah S. et al. A Detailed Immunohistochemical Analysis of a Large Series of Cervical and Vaginal Gastric-type Adenocarcinomas. Am J Surg Pathol 2016; 40: 636-644
• 38 Parra-Herran C, Taljaard M, Djordjevic B. et al. Pattern-based classification of invasive endocervical adenocarcinoma, depth of invasion measurement and distinction from adenocarcinoma in situ: interobserver variation among gynecologic pathologists. Mod Pathol 2016; 29: 879-892
• 39 Ip PP. Benign endometrial proliferations mimicking malignancies: a review of problematic entities in small biopsy specimens. Virchows Arch 2018; 472: 907-917
• 40 Howitt BE, Quade BJ, Nucci MR. Uterine polyps with features overlapping with those of Müllerian adenosarcoma: a clinicopathologic analysis of 29 cases emphasizing their likely benign nature. Am J Surg Pathol 2015; 39: 116-126
• 41 McCluggage WG. A practical approach to the diagnosis of mixed epithelial and mesenchymal tumours of the uterus. Mod Pathol 2016; 29 (Suppl. 01) S78-S91
• 42 Knopp S, Bjørge T, Nesland JM. et al. p16INK4a and p21Waf1/Cip1 expression correlates with clinical outcome in vulvar carcinomas. Gynecol Oncol 2004; 95: 37-45
• 43 Roma AA, Mistretta T-A, Diaz De Vivar A. et al. New pattern-based personalized risk stratification system for endocervical adenocarcinoma with important clinical implications and surgical outcome. Gynecol Oncol 2016; 141: 36-42
• 44 Höckel M, Trott S, Dornhöfer N. et al. Vulvar field resection based on ontogenetic cancer field theory for surgical treatment of vulvar carcinoma: a single-centre, single-group, prospective trial. Lancet Oncol 2018; 19: 537-548