{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T21:37:11Z","timestamp":1793655431256,"version":"4.5.1"},"reference-count":115,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2025,6,25]],"date-time":"2025-06-25T00:00:00Z","timestamp":1750809600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: Vaginal adenocarcinoma is a rare malignancy, accounting for less than 10% of all primary vaginal cancers. It predominantly affects older women but can also occur in younger populations, particularly in association with in utero diethylstilbestrol (DES) exposure. Given its rarity, evidence regarding the optimal management of vaginal adenocarcinoma remains limited. This review aimed to summarize the current understanding of vaginal adenocarcinoma, covering the epidemiology, etiology, diagnostic approaches, treatment modalities, prognosis, and areas requiring further investigation thereof. Methods: We conducted a search for the term \u201cvaginal adenocarcinoma\u201d in the PubMed, Scopus, and Web of Science databases from January 2016 to 28 April 2025. Results: Overall, 83 articles were included in the final review. Among them, 21 cases of vaginal adenocarcinoma were reported. Vaginal adenocarcinoma demonstrates a bimodal age distribution, with clear cell histology commonly linked to DES exposure and endometrioid or mucinous types seen in older patients. Risk factors include DES exposure, chronic inflammation, and human papillomavirus (HPV) infection. The diagnosis relies on a pelvic examination, imaging, and biopsy. Treatment typically involves surgery, radiotherapy, or a combination thereof, tailored to the stage and location, with chemotherapy reserved for advanced cases. The prognosis depends on the histologic subtype, tumor size, stage, and treatment response, with early-stage disease generally associated with better outcomes. Conclusions: Improved awareness of risk factors and early diagnostic strategies is critical to optimize patient outcomes. Research is needed to refine treatment protocols, explore targeted therapies and immunotherapy, and investigate the molecular underpinnings of vaginal adenocarcinoma, particularly non-DES-associated types.<\/jats:p>","DOI":"10.3390\/cancers17132130","type":"journal-article","created":{"date-parts":[[2025,6,25]],"date-time":"2025-06-25T08:23:22Z","timestamp":1750839802000},"page":"2130","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Vaginal Adenocarcinoma: A Review of a Rare Gynecologic Cancer"],"prefix":"10.3390","volume":"17","author":[{"given":"Mun-Kun","family":"Hong","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Tzu Chi University, Hualien 970, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5105-068X","authenticated-orcid":false,"given":"Dah-Ching","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Tzu Chi University, Hualien 970, Taiwan"},{"name":"Institute of Medical Sciences, Tzu Chi University, Hualien 970, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1016\/j.bpobgyn.2015.01.006","article-title":"Staging for Vaginal Cancer","volume":"29","author":"Rajaram","year":"2015","journal-title":"Best Pract. Res. Clin. Obstet. Gynaecol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"101309","DOI":"10.1016\/j.gore.2023.101309","article-title":"Malignant Neoplasms of the Vagina: A 30-Year Review from the Republic of Belarus","volume":"50","author":"Matylevich","year":"2023","journal-title":"Gynecol. Oncol. Rep."},{"key":"ref_3","first-page":"S84","article-title":"Cancer of the Vagina","volume":"131","author":"Hacker","year":"2015","journal-title":"Int. J. Gynaecol. Obstet."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Lee, H., Kim, H., and Kim, H.-S. (2022). Mesonephric Adenocarcinoma of the Vagina Harboring TP53 Mutation. Diagnostics, 12.","DOI":"10.3390\/diagnostics12010119"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Pang, L., Li, L., Zhu, L., Lang, J., and Bi, Y. (2019). Malignant Transformation of Vaginal Adenosis to Clear Cell Carcinoma Without Prenatal Diethylstilbestrol Exposure: A Case Report and Literature Review. BMC Cancer, 19.","DOI":"10.1186\/s12885-019-6026-1"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Baral, S.K., Biswas, P., Kaium, M.A., Islam, M.A., Dey, D., Saber, M.A., Rahaman, T.I., Emran, T.B., Hasan, M.N., and Jeong, M.K. (2022). A Comprehensive Discussion in Vaginal Cancer Based on Mechanisms, Treatments, Risk Factors and Prevention. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.883805"},{"key":"ref_7","first-page":"e25298","article-title":"Primary Vaginal Adenocarcinoma of Intestinal-Type: A Case Report of a Rare Tumor with Review of Histology, Differential Diagnosis, and Literature","volume":"14","author":"Sabri","year":"2022","journal-title":"Cureus"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1002\/pbc.20113","article-title":"Adenocarcinoma of the Cervix and Vagina in Pediatric Patients","volume":"43","author":"McNall","year":"2004","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e13852","DOI":"10.1097\/MD.0000000000013852","article-title":"Adenoid Cystic Carcinoma of the Vagina: A Case Report","volume":"98","author":"Zhang","year":"2019","journal-title":"Medicine"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Shen, Y., Meng, X., Wang, L., Wang, X., and Chang, H. (2022). Advanced Primary Vaginal Squamous Cell Carcinoma: A Case Report and Literature Review. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.1007462"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"101160","DOI":"10.1016\/j.gore.2023.101160","article-title":"A Complete Durable Response of Vaginal Clear Cell Carcinoma with Pembrolizumab: A Case Report","volume":"49","author":"Guntupalli","year":"2023","journal-title":"Gynecol. Oncol. Rep."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Ferrari, F., Omodei, A.S., Ferrari, F.A., Soleymani Majd, H., Ardighieri, L., Vitale, S.G., Lagan\u00e0, A.S., Angioni, S., Ciravolo, G., and Odicino, F. (2023). Diagnosis, Treatment and Prognosis of Mesonephric Adenocarcinoma of the Vagina: A Literature Review and a Case Report. J. Clin. Med., 12.","DOI":"10.3390\/jcm12144846"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1186\/s12957-019-1743-0","article-title":"Endometrioid Adenocarcinoma of the Rectovaginal Septum with Invasion of the Rectum: A Case Report and Review of Literature","volume":"17","author":"Yang","year":"2019","journal-title":"World J. Surg. Oncol."},{"key":"ref_14","first-page":"941","article-title":"Endometrioid Adenocarcinoma of the Rectovaginal Septum: A Case Report","volume":"48","author":"Mu","year":"2023","journal-title":"Zhong Nan Da Xue Xue Bao Yi Xue Ban"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.5306\/wjco.v15.i8.1102","article-title":"Individualized Vaginal Applicator for Stage IIb Primary Vaginal Adenocarcinoma: A Case Report","volume":"15","author":"Saijilafu","year":"2024","journal-title":"World J. Clin. Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"NP67","DOI":"10.1177\/03008916211007930","article-title":"Is a Tailored Strategy Using Proton Beam Radiotherapy for Reirradiation Advantageous for Elderly Women? A Case Report","volume":"107","author":"Barcellini","year":"2021","journal-title":"Tumori"},{"key":"ref_17","first-page":"157","article-title":"Non-Diethylstilbestrol Exposed Vaginal Adenocarcinoma in Young Patients Associated with Unilateral Renal Agenesis: Two Case Reports and Literature Review","volume":"38","author":"Jankovic","year":"2017","journal-title":"Eur. J. Gynaecol. Oncol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"277","DOI":"10.4103\/jcrt.JCRT_168_19","article-title":"Post Hysterectomy Mesonephric Carcinoma: A Case Report and Literature Review","volume":"18","author":"Kumar","year":"2022","journal-title":"J. Cancer Res. Ther."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e33285","DOI":"10.1097\/MD.0000000000033285","article-title":"Primary Clear Cell Adenocarcinoma of the Rectovaginal Septum: A Rare Case Report","volume":"102","author":"Li","year":"2023","journal-title":"Medicine"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"107460","DOI":"10.1016\/j.ijscr.2022.107460","article-title":"Primary Clear Cell Adenocarcinoma of the Vagina Not Associated with Diethylstilbestrol: A Case Report","volume":"98","author":"Haddout","year":"2022","journal-title":"Int. J. Surg. Case Rep."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1177\/10668969221150529","article-title":"Primary HPV-Associated Enteric-Type Adenocarcinoma of Vagina: A Case Report","volume":"31","author":"Felicelli","year":"2023","journal-title":"Int. J. Surg. Pathol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"omz088","DOI":"10.1093\/omcr\/omz088","article-title":"Primary Vaginal Adenocarcinoma of Intestinal-Type: Case Report of a Rare Gynaecological Tumour","volume":"2019","author":"Ugwu","year":"2019","journal-title":"Oxf. Med. Case Rep."},{"key":"ref_23","first-page":"2784","article-title":"Primary Vaginal Clear Cell Adenocarcinoma Accompanied by Herlyn-Werner-Wunderlich Syndrome Without Prenatal Diethylstilbestrol Exposure: A Case Report","volume":"13","author":"Mei","year":"2020","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Warembourg, S., Cayrac, M., Rathat, G., and Rafii, A. (2016). Recto-Vaginal Septum Cystadenocarcinoma: A Case Report and Review of the Literature. BMC Women\u2019s. Health, 16.","DOI":"10.1186\/s12905-016-0300-z"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1002\/ijgo.14603","article-title":"Small-Cell Neuroendocrine Carcinoma of the Vagina: A Case Report","volume":"161","author":"Kalampokas","year":"2023","journal-title":"Int. J. Gynaecol. Obstet."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"101768","DOI":"10.1016\/j.jogoh.2020.101768","article-title":"Use of Fluorescence to Guide Surgical Resection in Vulvo-Vaginal Neoplasia: Two Case Reports","volume":"50","author":"Koual","year":"2021","journal-title":"J. Gynecol. Obstet. Hum. Reprod."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.5306\/wjco.v15.i10.1359","article-title":"Vaginal Clear Cell Adenocarcinoma in Herlyn-Werner-Wunderlich Syndrome: A Case Report","volume":"15","author":"Lei","year":"2024","journal-title":"World J. Clin. Oncol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.pathol.2017.11.084","article-title":"Mesonephric Proliferations of the Female Genital Tract","volume":"50","author":"Howitt","year":"2018","journal-title":"Pathology"},{"key":"ref_29","first-page":"268","article-title":"Gynecological Cancer Age Groups at the \u201cDr. Salvator Vuia\u201d Clinical Obstetrics and Gynecology Hospital During the 2000-2009 Period","volume":"6","author":"Furau","year":"2011","journal-title":"Maedica"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2873","DOI":"10.1002\/cncr.23757","article-title":"Descriptive Epidemiology of Vaginal Cancer Incidence and Survival by Race, Ethnicity, and Age in the United States","volume":"113","author":"Wu","year":"2008","journal-title":"Cancer"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1002\/ijgo.12610","article-title":"Cancer of the Vagina","volume":"143","author":"Adams","year":"2018","journal-title":"Int. J. Gynaecol. Obstet."},{"key":"ref_32","unstructured":"Devita, V.T., Lawrence, T.S., and Rosenberg, S.A. (2019). Cancer of the Cervix, Vagina, and Vulva. Devita, Hellman, and Rosenberg\u2019s Cancer: Principles and Practice of Oncology, Lippincott Williams & Wilkins."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1660","DOI":"10.1111\/1471-0528.17887","article-title":"Incidence Distributions, Risk Factors and Trends of Vaginal Cancer: A Global Population-Based Study","volume":"131","author":"Huang","year":"2024","journal-title":"BJOG"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1016\/0002-9378(74)90138-0","article-title":"Clear-Cell Adenocarcinoma of the Vagina and Cervix in Girls: Analysis of 170 Registry Cases","volume":"119","author":"Herbst","year":"1974","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1056\/NEJM197104222841604","article-title":"Adenocarcinoma of the Vagina. Association of Maternal Stilbestrol Therapy with Tumor Appearance in Young Women","volume":"284","author":"Herbst","year":"1971","journal-title":"N. Engl. J. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1002\/1097-0142(197004)25:4<745::AID-CNCR2820250402>3.0.CO;2-2","article-title":"Adenocarcinoma of the Vagina in Adolescence. A Report of 7 Cases Including 6 Clear-Cell Carcinomas (so-Called Mesonephromas)","volume":"25","author":"Herbst","year":"1970","journal-title":"Cancer"},{"key":"ref_37","first-page":"309","article-title":"Pathologic Findings in Young Women Enrolled in the National Cooperative Diethylstilbestrol Adenosis (DESAD) Project","volume":"53","author":"Robboy","year":"1979","journal-title":"Obstet. Gynecol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1016\/S0002-9378(16)38617-3","article-title":"Does the Administration of Diethylstilbestrol During Pregnancy Have Therapeutic Value?","volume":"66","author":"Dieckmann","year":"1953","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/S0002-9378(16)40020-7","article-title":"Increased Excretion of Pregnanediol in Pregnancy from Diethylstilbestrol with Special Reference to the Prevention of Late Pregnancy Accidents","volume":"51","author":"Smith","year":"1946","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1016\/0002-9378(48)90440-2","article-title":"Diethylstilbestrol in the Prevention and Treatment of Complications of Pregnancy","volume":"56","author":"Smith","year":"1948","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1016\/0002-9378(79)90814-7","article-title":"Epidemiologic Aspects and Factors Related to Survival in 384 Registry Cases of Clear Cell Adenocarcinoma of the Vagina and Cervix","volume":"135","author":"Herbst","year":"1979","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1055\/a-1545-4279","article-title":"2020 WHO Classification of Female Genital Tumors","volume":"81","author":"Brambs","year":"2021","journal-title":"Geburtshilfe Frauenheilkd."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1038\/s41379-021-00942-3","article-title":"Molecular Landscape of Vulvovaginal Squamous Cell Carcinoma: New Insights into Molecular Mechanisms of HPV-Associated and HPV-Independent Squamous Cell Carcinoma","volume":"35","author":"Salama","year":"2022","journal-title":"Mod. Pathol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1038\/s41379-019-0437-z","article-title":"A Novel Group of HPV-Related Adenocarcinomas of the Lower Anogenital Tract (Vagina, Vulva, and Anorectum) in Women and Men Resembling HPV-Related Endocervical Adenocarcinomas","volume":"33","author":"Voltaggio","year":"2020","journal-title":"Mod. Pathol."},{"key":"ref_45","unstructured":"Kaltenecker, B., Dunton, C.J., and Tikaria, R. (2025). Vaginal Cancer. StatPearls, StatPearls Publishing."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1002\/ijgo.13867","article-title":"Cancer of the Vagina: 2021 Update","volume":"155","author":"Adams","year":"2021","journal-title":"Int. J. Gynaecol. Obstet."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Paspulati, R.M. (2011). Carcinoma of the Vagina and Vulva. Gynecologic Imaging, Elsevier.","DOI":"10.1016\/B978-1-4377-1575-0.10035-0"},{"key":"ref_48","unstructured":"Barakat, R.R., Markman, M., and Randall, M.E. (2009). Chapter 20: Vagina. Principles and Practice of Gynecologic Oncology, Lippincott Williams and Wilkins."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Betova, T., Trifonov, R., Popovska, S., Yordanov, A., Karakadieva, K., Dancheva, Z., and Kostov, S. (2024). Primary Vaginal Mucinous Adenocarcinoma of Intestinal Type-Clinical, Radiological and Morphological Aspects. Medicina, 60.","DOI":"10.3390\/medicina60040525"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e22405","DOI":"10.1016\/j.heliyon.2023.e22405","article-title":"Diagnostic Efficacy of Intraoperative Histopathological Examination of Lesions with Unknown Diagnosis Suspicious for Malignancy","volume":"9","author":"Tekneci","year":"2023","journal-title":"Heliyon"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1136\/ijgc-2023-004695","article-title":"ESTRO\/ESGO\/SIOPe Guidelines for the Management of Patients with Vaginal Cancer","volume":"33","author":"Nout","year":"2023","journal-title":"Int. J. Gynecol. Cancer"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"20150033","DOI":"10.1259\/bjr.20150033","article-title":"Primary Vaginal Cancer: Role of MRI in Diagnosis, Staging and Treatment","volume":"88","author":"Gardner","year":"2015","journal-title":"Br. J. Radiol."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Ebrahimi, S., Lundstr\u00f6m, E., Batasin, S.J., Hedlund, E., St\u00e5lberg, K., Ehman, E.C., Sheth, V.R., Iranpour, N., Loubrie, S., and Schlein, A. (2024). Application of PET\/MRI in Gynecologic Malignancies. Cancers, 16.","DOI":"10.3390\/cancers16081478"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1097\/PGP.0b013e3182a54afa","article-title":"PAX8 Expression in Uterine Adenocarcinomas and Mesonephric Proliferations","volume":"33","author":"Yemelyanova","year":"2014","journal-title":"Int. J. Gynecol. Pathol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"100614","DOI":"10.1016\/j.gore.2020.100614","article-title":"Novel Immunohistochemical Markers in the Differential Diagnosis of Endocervical and Endometrial Adenocarcinoma: The Added Benefit of CAIX and PAX8","volume":"33","author":"Vierkoetter","year":"2020","journal-title":"Gynecol. Oncol. Rep."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"449","DOI":"10.5468\/ogs.24120","article-title":"The Evolving Landscape of Immunohistochemistry in Cervical and Uterine Carcinoma in Gynecologic Oncology: Current Status and Future Directions","volume":"67","author":"Gupta","year":"2024","journal-title":"Obstet. Gynecol. Sci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1097\/00004347-199707000-00017","article-title":"Primary Serous Papillary Adenocarcinoma of the Vagina: A Case Report","volume":"16","author":"Riva","year":"1997","journal-title":"Int. J. Gynecol. Pathol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1006\/gyno.2001.6171","article-title":"The Role of Surgery in Invasive Squamous Carcinoma of the Vagina","volume":"81","author":"Tjalma","year":"2001","journal-title":"Gynecol. Oncol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1006\/gyno.1995.1008","article-title":"A 30-Year Experience in the Management of Primary Carcinoma of the Vagina: Analysis of Prognostic Factors and Treatment Modalities","volume":"56","author":"Stock","year":"1995","journal-title":"Gynecol. Oncol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1016\/0090-8258(85)90216-1","article-title":"Squamous Carcinoma of the Vagina: Treatment, Complications, and Long-Term Follow-Up","volume":"20","author":"Rubin","year":"1985","journal-title":"Gynecol. Oncol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.critrevonc.2014.09.002","article-title":"Squamous Cell Carcinoma of the Vagina: Natural History, Treatment Modalities and Prognostic Factors","volume":"93","author":"Gadducci","year":"2015","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1016\/j.ygyno.2020.08.036","article-title":"Management and Outcomes of Primary Vaginal Cancer","volume":"159","author":"Yang","year":"2020","journal-title":"Gynecol. Oncol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1634\/theoncologist.2017-0546","article-title":"Definitive Radiotherapy in Invasive Vaginal Carcinoma: A Systematic Review","volume":"24","author":"Guerri","year":"2019","journal-title":"Oncologist"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.ijrobp.2004.09.032","article-title":"Definitive Radiation Therapy for Squamous Cell Carcinoma of the Vagina","volume":"62","author":"Frank","year":"2005","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1016\/j.ygyno.2008.07.007","article-title":"Twenty-Year Review of Radiotherapy for Vaginal Cancer: An Institutional Experience","volume":"111","author":"Lian","year":"2008","journal-title":"Gynecol. Oncol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.radonc.2019.11.005","article-title":"Recommendations from Gynaecological (GYN) GEC-ESTRO Working Group\u2014ACROP: Target Concept for Image Guided Adaptive Brachytherapy in Primary Vaginal Cancer","volume":"145","author":"Schmid","year":"2020","journal-title":"Radiother. Oncol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1136\/ijgc-00009577-200201000-00005","article-title":"High-Dose-Rate Brachytherapy for Vaginal Cancer: Learning from Treatment Complications","volume":"12","author":"Tyree","year":"2002","journal-title":"Int. J. Gynecol. Cancer"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/j.ygyno.2014.09.018","article-title":"Adoption and Impact of Concurrent Chemoradiation Therapy for Vaginal Cancer: A National Cancer Data Base (NCDB) Study","volume":"135","author":"Rajagopalan","year":"2014","journal-title":"Gynecol. Oncol."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Miyamoto, D.T., and Viswanathan, A.N. (2013). Concurrent Chemoradiation for Vaginal Cancer. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0065048"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"416","DOI":"10.5468\/ogs.2013.56.6.416","article-title":"Vaginal Cancer with Multiple Liver and Pulmonary Metastases That Achieved Long-Term Survival","volume":"56","author":"Kim","year":"2013","journal-title":"Obstet. Gynecol. Sci."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1856","DOI":"10.1056\/NEJMoa2112435","article-title":"Pembrolizumab for Persistent, Recurrent, or Metastatic Cervical Cancer","volume":"385","author":"Colombo","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"7091","DOI":"10.21037\/tcr-20-1825","article-title":"Survival and Prognostic Factors in Primary Vaginal Cancer: An Analysis of 2004-2014 SEER Data","volume":"9","author":"Huang","year":"2020","journal-title":"Transl. Cancer Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2144","DOI":"10.1111\/aogs.14260","article-title":"The Prognostic Significance of HPV, p16, and p53 Protein Expression in Vaginal Cancer: A Systematic Review","volume":"100","author":"Rasmussen","year":"2021","journal-title":"Acta Obstet. Gynecol. Scand."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Zafar, M., Sweis, N., Kapoor, H., and Gantt, G. (2025). Advances and Challenges in the Treatment of HPV-Associated Lower Genital Tract Cancers by Immune Checkpoint Blockers: Insights from Basic and Clinical Science. Cancers, 17.","DOI":"10.3390\/cancers17081260"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1136\/ijgc-2021-002517","article-title":"Updates in the Treatment of Vaginal Cancer","volume":"32","author":"Jhingran","year":"2022","journal-title":"Int. J. Gynecol. Cancer"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1097\/IGC.0000000000000012","article-title":"Pattern of Cancer Recurrence in 320 Patients after Radical Vaginal Trachelectomy","volume":"24","author":"Mangler","year":"2014","journal-title":"Int. J. Gynecol. Cancer"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Micc\u00f2, M., Lupinelli, M., Mangialardi, M., Gui, B., and Manfredi, R. (2022). Patterns of Recurrent Disease in Cervical Cancer. J. Pers. Med., 12.","DOI":"10.3390\/jpm12050755"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1002\/(SICI)1097-0142(19980901)83:5<1033::AID-CNCR30>3.0.CO;2-6","article-title":"The National Cancer Data Base Report on Cancer of the Vagina","volume":"83","author":"Creasman","year":"1998","journal-title":"Cancer"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.3332\/ecancer.2021.1267","article-title":"Twenty Years\u2019 Experience of Primary Vaginal Cancer Treatment at One Cancer Centre: Does Residence Status Matter?","volume":"15","author":"Matylevich","year":"2021","journal-title":"Ecancermedicalscience"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1746","DOI":"10.1056\/NEJMc1800097","article-title":"Follow-up of Patients with Clear-Cell Adenocarcinoma of the Vagina and Cervix","volume":"378","author":"Huo","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1016\/j.ygyno.2017.06.028","article-title":"Incidence Rates and Risks of Diethylstilbestrol-Related Clear-Cell Adenocarcinoma of the Vagina and Cervix: Update after 40-Year Follow-Up","volume":"146","author":"Huo","year":"2017","journal-title":"Gynecol. Oncol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1971","DOI":"10.1002\/1097-0142(19910401)67:7<1971::AID-CNCR2820670725>3.0.CO;2-X","article-title":"Clear Cell Adenocarcinoma of the Vagina and Cervix. A Report of the Central Netherlands Registry with Emphasis on Early Detection and Prognosis","volume":"67","author":"Hanselaar","year":"1991","journal-title":"Cancer"},{"key":"ref_83","first-page":"235","article-title":"Laparoscopic Ovarian Transposition and Ovariopexy for Fertility Preservation in Patients Treated with Pelvic Radiotherapy with or Without Chemotherapy","volume":"11","author":"Turkgeldi","year":"2019","journal-title":"Facts Views Vis. ObGyn"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1016\/j.ygyno.2007.01.049","article-title":"Fertility-Sparing Radical Abdominal Trachelectomy for Clear Cell Adenocarcinoma of the Upper Vagina: A Case Report","volume":"105","author":"Matthews","year":"2007","journal-title":"Gynecol. Oncol."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"K\u00e1llay, \u00c9., M\u00fcller-Fabian, A., and D\u00e9gi, C.L. (2024). Fear of Cancer Progression and the Quality of Sexual Life of Female Cancer Patients in Romania. Front. Public Health, 12.","DOI":"10.3389\/fpubh.2024.1417681"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1294","DOI":"10.5498\/wjp.v14.i9.1294","article-title":"Impact of Gynecological Cancers on Women\u2019s Mental Health","volume":"14","author":"Marano","year":"2024","journal-title":"World J. Psychiatry"},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Mohamad Muhit, A.M., Sy-Cherng Woon, L., Nik Mhd Nor, N.S., Sidi, H., Mohd Kalok, A.H., Kampan, N.C., and Shafiee, M.N. (2022). Sexual Dysfunction Among Gynaecological Cancer Survivors: A Descriptive Cross-Sectional Study in Malaysia. Int. J. Environ. Res. Public Health, 19.","DOI":"10.3390\/ijerph192315545"},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Malandrone, F., Bevilacqua, F., Merola, M., Gallio, N., Ostacoli, L., Carletto, S., and Benedetto, C. (2021). The Impact of Vulvar Cancer on Psychosocial and Sexual Functioning: A Literature Review. Cancers, 14.","DOI":"10.3390\/cancers14010063"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"3128","DOI":"10.1111\/j.1365-2702.2011.03728.x","article-title":"A Literature Review of the Impact of a Diagnosis of Cancer of the Vulva and Surgical Treatment","volume":"20","author":"Jefferies","year":"2011","journal-title":"J. Clin. Nurs."},{"key":"ref_90","first-page":"112","article-title":"Consequences of Gynecological Cancer in Patients and Their Partners from the Sexual and Psychological Perspective","volume":"15","year":"2016","journal-title":"Prz. Menopauzalny"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1037\/fam0000168","article-title":"Effects of Economic Hardship: Testing the Family Stress Model over Time","volume":"30","author":"Neppl","year":"2016","journal-title":"J. Fam. Psychol."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Zhao, J., Kong, Y., Xiang, Y., and Yang, J. (2023). The Research Landscape of the Quality of Life or Psychological Impact on Gynecological Cancer Patients: A Bibliometric Analysis. Front. Oncol., 13.","DOI":"10.3389\/fonc.2023.1115852"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1016\/j.ccell.2017.04.013","article-title":"A Pan-Cancer Proteogenomic Atlas of PI3K\/AKT\/mTOR Pathway Alterations","volume":"31","author":"Zhang","year":"2017","journal-title":"Cancer Cell"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"4809751","DOI":"10.1155\/2017\/4809751","article-title":"A Review of mTOR Pathway Inhibitors in Gynecologic Cancer","volume":"2017","author":"Paulino","year":"2017","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.semcancer.2019.05.012","article-title":"Role of the PI3K\/AKT\/mTOR Signaling Pathway in Ovarian Cancer: Biological and Therapeutic Significance","volume":"59","author":"Ediriweera","year":"2019","journal-title":"Semin. Cancer Biol."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Peng, Y., Wang, Y., Zhou, C., Mei, W., and Zeng, C. (2022). PI3K\/Akt\/mTOR Pathway and Its Role in Cancer Therapeutics: Are We Making Headway?. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.819128"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1200\/JCO.19.02105","article-title":"Efficacy of Pembrolizumab in Patients with Noncolorectal High Microsatellite Instability\/mismatch Repair-Deficient Cancer: Results from the Phase II KEYNOTE-158 Study","volume":"38","author":"Marabelle","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1038\/bjc.1995.288","article-title":"TP53 Gene Mutations and Protein Accumulation in Primary Vaginal Carcinomas","volume":"72","author":"Skomedal","year":"1995","journal-title":"Br. J. Cancer"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1097\/PGP.0b013e31822c8036","article-title":"Primary Vaginal Mucinous Adenocarcinoma of Gastric Type Arising in Adenosis: A Report of 2 Cases, 1 Associated with Uterus Didelphys","volume":"31","author":"Talia","year":"2012","journal-title":"Int. J. Gynecol. Pathol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1006\/gyno.1996.0052","article-title":"P53 Protein Expression and Gene Analysis in Clear Cell Adenocarcinoma of the Vagina and Cervix","volume":"60","author":"Waggoner","year":"1996","journal-title":"Gynecol. Oncol."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Chung, T.K.H., Doran, G., Cheung, T.-H., Yim, S.-F., Yu, M.-Y., Worley, M.J., Elias, K.M., Thorner, A.R., Pedamallu, C.S., and Ojesina, A.I. (2021). Dissection of PIK3CA Aberration for Cervical Adenocarcinoma Outcomes. Cancers, 13.","DOI":"10.3390\/cancers13133218"},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Voutsadakis, I.A. (2021). PI3KCA Mutations in Uterine Cervix Carcinoma. J. Clin. Med., 10.","DOI":"10.3390\/jcm10020220"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.ygyno.2024.02.029","article-title":"Alpelisib for PIK3CA-Mutated Advanced Gynecological Cancers: First Clues of Clinical Activity","volume":"183","author":"Passarelli","year":"2024","journal-title":"Gynecol. Oncol."},{"key":"ref_104","first-page":"19","article-title":"PTEN Gene and AKT\/mTOR Pathway in Gynecological Cancers and Cancer Immune Escape","volume":"43","author":"Zeng","year":"2022","journal-title":"Eur. J. Gynaecol. Oncol."},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Bossler, F., Hoppe-Seyler, K., and Hoppe-Seyler, F. (2019). PI3K\/AKT\/mTOR Signaling Regulates the Virus\/host Cell Crosstalk in HPV-Positive Cervical Cancer Cells. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20092188"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"4163","DOI":"10.1002\/jcb.26118","article-title":"The Potential Value of the PI3K\/Akt\/mTOR Signaling Pathway for Assessing Prognosis in Cervical Cancer and as a Target for Therapy","volume":"118","author":"Bahrami","year":"2017","journal-title":"J. Cell. Biochem."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1053\/j.semdp.2020.09.010","article-title":"Molecular Events in the Pathogenesis of Vulvar Squamous Cell Carcinoma","volume":"38","author":"Xing","year":"2021","journal-title":"Semin. Diagn. Pathol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1016\/j.ygyno.2018.06.026","article-title":"Somatic Mutation Profiling of Vulvar Cancer: Exploring Therapeutic Targets","volume":"150","author":"Kowalik","year":"2018","journal-title":"Gynecol. Oncol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"eaay0152","DOI":"10.1126\/scitranslmed.aay0152","article-title":"PTEN Status Determines Chemosensitivity to Proteasome Inhibition in Cholangiocarcinoma","volume":"12","author":"Jiang","year":"2020","journal-title":"Sci. Transl. Med."},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Cho, Y.S., Kim, H.R., Park, S.J., Chung, S.W., Ko, Y.G., Yeo, J.H., Lee, J., Kim, S.K., Choi, J.U., and Kim, S.Y. (2022). Sustained Potentiation of Bystander Killing via PTEN-Loss Driven Macropinocytosis Targeted Peptide-Drug Conjugate Therapy in Metastatic Triple-Negative Breast Cancer. Biomaterials, 289.","DOI":"10.1016\/j.biomaterials.2022.121783"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"969","DOI":"10.18632\/oncotarget.27503","article-title":"Targeting PI3K\u03b2 Alone and in Combination with Chemotherapy or Immunotherapy in Tumors with PTEN Loss","volume":"11","author":"Zhao","year":"2020","journal-title":"Oncotarget"},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Gonz\u00e1lez-Garc\u00eda, A., Garrido, A., and Carrera, A.C. (2022). Targeting PTEN Regulation by Post Translational Modifications. Cancers, 14.","DOI":"10.3390\/cancers14225613"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1097\/PGP.0000000000001050","article-title":"Targetable ERBB2\/HER2 Mutations in Gynecologic Malignancies: Clinicopathological, Immunohistochemical, and Molecular Correlations","volume":"44","author":"Manrai","year":"2025","journal-title":"Int. J. Gynecol. 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