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Vaginal Cancer

Cancer of the vagina is relatively rare, accounting for about 2% of gynaecological malignancies. There are two main types of vaginal cancer; squamous cell cancer and adenocarcinoma. Over four fifths of all vaginal cancers are squamous carcinoma, this is more common in women between the ages of 60 and 80. The other type of vaginal cancer; adenocarcinoma is usually found in young women under 30 years old.

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  • PubMed search for publications about Vaginal Cancer - Limit search to: [Reviews]

    PubMed Central search for free-access publications about Vaginal Cancer
    MeSH term: Vaginal Neoplasms
    International US National Library of Medicine
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Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Agarwal P, Kaushal M
Cytology of primary vaginal melanoma: An unusual report on fine needle aspiration.
Diagn Cytopathol. 2017; 45(3):252-256 [PubMed] Related Publications
Primary malignant melanoma of the vagina is an extremely uncommon malignancy comprising of less than 10% malignancies of the female genital tract and 0.3% of all melanomas. Melanoblasts are neural crest derivatives and are notorious for causing primary cutaneous neoplasms. However, they involve virtually every organ of the body including eye, intestines and ocular mucosa, probably due to aberrancies in cell migration. Vagina is a rare site and primary melanoma of the vagina occurs in postmenopausal women with vaginal discharge, bleeding, or mass as common presenting complaints. Only a handful of case reports are available describing this entity on biopsy and PAP smear samples; however, fine needle aspiration has seldom been discussed. In the present report we discuss a case of an elderly female who complained of mass protruding through the vaginal opening, FNAC was done from the mass as well as from the right inguinal lymph node. An extensive clinicoradiological workup, and immunohistochemical confirmation is essential to rule out metastatic lesions and confirm primary. Diagn. Cytopathol. 2017;45:252-256. © 2016 Wiley Periodicals, Inc.

Chandrasekaran N, Scharifker D, Varsegi G, Almeida Z
Breast metastasis from vaginal cancer.
BMJ Case Rep. 2016; 2016 [PubMed] Related Publications
Vaginal cancer is a rare malignancy accounting for 1-2% of all pelvic neoplasms. Dissemination usually occurs through local invasion and rarely metastasises to distal locations. Metastasis of vaginal cancer to the breast is extremely infrequent and unique. A 66-year-old Asian woman presented with vaginal bleeding and was found to have a vaginal mass and a left breast mass. Pathological assessment of the biopsies revealed identical squamous cell characteristics of both masses. We describe a very rare and novel case of a distally located vaginal carcinoma with metastasis to the breast Federation of Gynecology and Obstetrics (FIGO) stage IV (FIGO IVB). Robot-assisted extrafascial total hysterectomy with local vaginal mass excision and partial mastectomy of the left breast were performed. After surgery, the patient underwent adjuvant chemotherapy followed by breast and pelvic radiotherapy, with maintained complete remission after 3 years of follow-up. This combination of findings and treatment is very distinct with a unique and favourable response.

Siegler E, Segev Y, Mackuli L, et al.
Vulvar and Vaginal Cancer, Vulvar Intraepithelial Neoplasia 3 and Vaginal Intraepithelial Neoplasia 3: Experience of a Referral Institute.
Isr Med Assoc J. 2016; 18(5):286-9 [PubMed] Related Publications
BACKGROUND: Vulvar and vaginal malignant and premalignant lesions are uncommon and are clinically heterogeneous diseases with two pathways of carcinogenesis: human papillomavirus (HPV) induced or non-HPV induced.
OBJECTIVES: To evaluate the demographic and clinical characteristics associated with vulvar or vaginal cancer and vulvar and vaginal intraepithelial neoplasia 3 (VIN3, VAIN3).
METHODS: We conducted a retrospective chart review of 148 women with vulvar and vaginal malignancy and pre-malignancy for the period October 2004 to October 2012, and identified 59 and 19 patients with vulvar and vaginal cancer respectively, and 57 and 13 patients with VIN3 and VAIN3 respectively
RESULTS: The median age of vulvar cancer patients was 30 years older than that of VIN3 patients. HPV was found in 60% and 66.6% of vulvar and vaginal cancer patients respectively, and in 82.3% and 84.6% of patients with VIN3 and VAIN3 respectively. A history of cervical intraepithelial neoplasia (CIN) or warts was observed in 10% and 10.5% of vulvar and vaginal cancer patients respectively, and in 57.9% and 46% of patients with VIN3 and VAIN3 respectively. In 52.6% of patients the vaginal cancer was metastases from other organs.
CONCLUSIONS: Most women with vulvar carcinoma are older than 70 years. VIN3 and VAIN3 are associated with HPV infection and the most prevalent type is HPV16. Almost half the vaginal cancers are associated with metastases from other organs and almost half of VAIN3 is associated with past cervical dysplasia or carcinoma.

Ladjevic IL, Stefanovic A, Kadija S, et al.
Vagina as a rare location of renal cell carcinoma metastasis.
Eur J Gynaecol Oncol. 2016; 37(3):434-5 [PubMed] Related Publications
INTRODUCTION: Metastatic renal cell carcinoma is often found in distant organs, including lung, bone, brain, and liver. Metastases to the vagina are extremely rare.
CASE REPORT: The authors present a case of renal cell carcinoma metastasis to the anterior vaginal wall four months after nephrectomy in a 56-year-old patient. The vaginal lesions were excised. After two years the patient had no signs of recurrence or the disease progression.
CONCLUSION: Vaginal metastases should be considered in differential diagnosis of female renal cell carcinoma patients presenting with vaginal bleeding of mass.

Gunes BY, Akbayır O, Demirci E, Ozaydin I
Clinical, pathological and (18)F-FDG PET/CT findings in synchronous primary vaginal and endometrial cancers.
Hell J Nucl Med. 2016 May-Aug; 19(2):170-2 [PubMed] Related Publications
Synchronous primary gynecologic malignancies are infrequently seen. In this report, we describe the clinical, pathological and fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) findings of a patient with synchronous primary vaginal and endometrial cancers. To our knowledge, this is the first such case described in the literature.

Lu W, Zhang X, Lu B
Benign intestinal glandular lesions in the vagina: a possible correlation with implantation.
Diagn Pathol. 2016; 11(1):52 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Enteric-type glandular lesions are extremely rare in the vagina. Their histological origin remains a matter of speculation at present.
METHOD: We review two rectal mucosal prolapse-like polyps and one intestinal-type adenosis in the vagina.
RESULTS: Case 1, a 64-year-old woman, presented with a vaginal polypoid lesion with a size of 4 × 3 × 3 cm. Case 2, an 8-year-old girl, had a 1.5 × 1.5 × 0.8-cm pedunculated polyp in the vaginal navicular fossa and a clinically suspected rectovaginal fistula. Case 1 and 3 had an obsolete severe perineal laceration. On histopathological examination, cases 1 and 2 resembled rectal mucosal prolapse or inflammatory cloacogenic polyp (rectal mucosal prolapse-like polyp). Case 3 had an incidental intestinal-type adenosis in the removed vaginal wall. Immunohistochemistry confirmed the intestinal differentiation in all 3 lesions by showing diffuse CDX2-positive, CK20-positive, and scattered chromogranin A-positive neuroendocrinal cells in the lower compartment of the crypt.
CONCLUSIONS: In summary, we report herein three unusual cases of benign intestinal-type glandular lesions in the vagina including two rectal mucosal prolapse-like polyps and one case of intestinal-type adenosis, and discuss possibilities for their histogenetic basis.

Lin DM, Barkan GA, Chatt G, et al.
Vaginal fine-needle aspiration: A useful alternative to biopsy.
Diagn Cytopathol. 2016; 44(8):665-9 [PubMed] Related Publications
BACKGROUND: Vaginal fine-needle aspiration (FNA) is infrequently performed to assess palpable lesions. We perform the first multi-institutional study to evaluate this procedure.
METHODS: We retrospectively reviewed vaginal FNAs performed at two institutions for the past 27 years. Clinical, cytological and histological data were reviewed and tabulated.
RESULTS: We identified 43 specimens from 39 patients (mean age 56 years, range 18-86 years). Twenty four patients (62%) had prior malignancies from the following sites: gynecologic tract (22), bladder (1), and breast (1). Twenty four specimens were malignant, 18 were benign (including eight cases from patients with prior malignancy) and one was unsatisfactory. Of 28 FNA specimens from patients with a malignant history, 18 (64%) were positive for malignancy. The most common malignancies were metastatic ovarian carcinoma (50%), squamous cell carcinoma (25%), and uterine cancer (17%). Mean time to metastasis/recurrence was 16 months and was longest in patients with ovarian metastasis (26 months) compared to other malignancies (P = 0.002). The most common benign diagnoses were cysts (33%) and inflammation (22%). In 27 cases with histological correlation, there were 20 true positives, six true negatives and one false negative (sensitivity =95%, specificity =100%). Seven patients had a recent Pap test with two true positives, two true negatives, and three false negatives (sensitivity = 40%, specificity = 100%).
CONCLUSION: Vaginal FNA is usually performed to rule out a secondary malignancy, often of ovarian origin. Vaginal metastases from extra-gynecologic sites are rare. FNA is both highly sensitive and specific and may be a safe and effective alternative to biopsy. Diagn. Cytopathol. 2016;44:665-669. © 2016 Wiley Periodicals, Inc.

Méry B, Ndong SM, Guy JB, et al.
Radiotherapy for gynecologic cancer in nonagenarian patients: a framework for new paradigms.
Chin J Cancer. 2016; 35:43 [PubMed] Free Access to Full Article Related Publications
No consensus exists regarding the role of radiotherapy in the management of gynecologic cancer in nonagenarian patients. We retrospectively reviewed the outcomes of 19 consecutive nonagenarian patients with gynecologic cancer (6 endometrial cancers, 6 cervical cancers, 4 vulvar cancers, and 3 vaginal cancers) who were treated with radiotherapy. Radiotherapy was performed mainly in a palliative setting (n = 12; 63.2%), with a median dose of 45 Gy (range, 6-76 Gy). Infrequent major acute or late toxicities were reported. Among 19 patients, 9 (47.4%) experienced tumor progression, 5 (26.3%) experienced complete response, 2 (10.5%) experienced stable disease and/or partial response. At last follow-up, 12 patients (63.2%) had died; most deaths (n = 9) occurred because of the cancer. These results suggest that radiotherapy is feasible in the treatment of nonagenarian patients with gynecologic cancer.

Visvalingam G, Lee WK, Wong CF, Lim YK
Primary malignant mixed Müllerian tumour (MMMT) of the vagina and review of the literature.
BMJ Case Rep. 2016; 2016 [PubMed] Related Publications
Primary malignant mixed Müllerian tumour (MMMT) of the vagina is a rare entity. We report a case of a 62-year-old woman who presented with a fixed and hard anterior vaginal wall mass with contact bleeding. She proceeded to have an anterior infralevator pelvic exenteration with urethrectomy and anterior vaginectomy, creation of an ileal conduit and bilateral lymph node dissection. Histopathological examination and immunohistochemistry confirmed the diagnosis of primary MMMT of the vagina. The patient was stage IVA at diagnosis. Despite chemotherapy and radiotherapy, she had progressive disease and eventually passed away at the age of 65 years.

Laliscia C, Fabrini MG, Delishaj D, et al.
Concomitant External-beam Irradiation and Chemotherapy Followed by High-dose Rate Brachytherapy Boost in the Treatment of Squamous Cell Carcinoma of the Vagina: A Single-Center Retrospective Study.
Anticancer Res. 2016; 36(4):1885-9 [PubMed] Related Publications
AIM: To assess the outcome of 35 patients with vaginal carcinoma treated with different radiotherapy modalities.
MATERIALS AND METHODS: Thirty-one patients received external-beam irradiation (EBRT) to the entire vagina, para-vaginal area and pelvic nodes (total dose=45-50.4 Gy). Concomitant chemotherapy was used in 22 patients. Nineteen patients received additional 15-25 Gy high-dose-rate brachytherapy (BT) boost and eight received additional EBRT boost to the primary tumor site. Four women received exclusive 30-40 Gy high-dose-rate BT.
RESULTS: Median progression-free survival and median overall survival were 22 months and 89 months, respectively. Age <70 years, use of EBRT plus BT, and concomitant chemotherapy were associated with better progression-free (p=0.002, p=0.007, and p=0.02) and overall (p=0.01, p=0.009, p=0.009) survival.
CONCLUSION: Concomitant EBRT and chemotherapy followed by BT is the best treatment for vaginal carcinoma.

Yan WX, Jia XJ, Chen YB, et al.
Primary small cell carcinoma of the vagina with pulmonary metastasis: a case report.
Eur J Gynaecol Oncol. 2016; 37(1):129-32 [PubMed] Related Publications
Primary small cell carcinoma of the vagina is extremely rare; no standard treatment has been established despite it being highly aggressive. Here, the authors report on a 43-year-old patient who had a mass on the clitoris and no uterine or bilateral adnexal involvement. Vaginal wall biopsy revealed malignant small cell carcinoma. The carcinoma was composed of epithelial cells with round, hyperchromatic nuclei containing few distinct nucleoli, and scanty cytoplasm. Chest computerized axial tomography and pathological bronchoscopy revealed bilateral pulmonary metastases. She received radiotherapy combined with six cycles of chemotherapy (paclitaxel plus cisplatin), and achieved complete response, with complete suppression of the mass and lung metastases. There was no sign of tumor recurrence or distant metastases after 21 months of follow-up.

Ngamkham J, Boonmark K, Phansri T
Detection and Type-Distribution of Human Papillomavirus in Vulva and Vaginal Abnormal Cytology Lesions and Cancer Tissues from Thai Women.
Asian Pac J Cancer Prev. 2016; 17(3):1129-34 [PubMed] Related Publications
Vulva and Vaginal cancers are rare among all gynecological cancers worldwide, including Thailand, and typically affect women in later life. Persistent high risk human papillomavirus (HR-HPV) infection is one of several important causes of cancer development. In this study, we focused on HPV investigation and specific type distribution from Thai women with abnormality lesions and cancers of the vulva and Vaginal. A total of ninety paraffin-embedded samples of vulva and Vaginal abnormalities and cancer cells with histologically confirmed were collected from Thai women, who were diagnosed in 2003-2012 at the National Cancer Institute, Thailand. HPV DNA was detected and genotyped using polymerase chain reaction and enzyme immunoassay with GP5+/ bio 6+ consensus specific primers and digoxigenin-labeled specific oligoprobes, respectively. The human β-globin gene was used as an internal control. Overall results represented that HPV frequency was 16/34 (47.1%) and 8/20 (40.0%) samples of vulva with cancer and abnormal cytology lesions, respectively, while, 3/5 (60%) and 16/33 (51.61%) samples of Vaginal cancer and abnormal cytology lesions, respectively, were HPV DNA positive. Single HPV type and multiple HPV type infection could be observed in both type of cancers and abnormal lesion samples in the different histological categorizes. HPV16 was the most frequent type in all cancers and abnormal cytology lesions, whereas HPV 18 was less frequent and could be detected as co-infection with other high risk HPV types. In addition, low risk types such as HPV 6, 11 and 70 could be detected in Vulva cancer and abnormal cytology lesion samples, whereas, all Vaginal cancer samples exhibited only high risk HPV types; HPV 16 and 31. In conclusion, from our results in this study we suggest that women with persistent high risk HPV type infection are at risk of developing vulva and Vaginal cancers and HPV 16 was observed at the highest frequent both of these, similar to the cervical cancer cases. Although the number of samples in this study was limited and might not represent the overall incidence and prevalence in Thai women, but the baseline data are of interest and suggest further study for primary cancer screening and/or developing the efficiency of prophylactic HPV vaccines in Thailand.

Sopracordevole F, Barbero M, Clemente N, et al.
High-grade vaginal intraepithelial neoplasia and risk of progression to vaginal cancer: a multicentre study of the Italian Society of Colposcopy and Cervico-Vaginal Pathology (SICPCV).
Eur Rev Med Pharmacol Sci. 2016; 20(5):818-24 [PubMed] Related Publications
OBJECTIVE: The aim of this study was to analyse the women with high grade vaginal intraepithelial neoplasia (HG-VaIN), in order to identify a subset of women at higher risk of progression to invasive vaginal cancer.
MATERIALS AND METHODS: The medical records of all the women diagnosed with HG-VaIN, and subsequently treated, from January 1995 to December 2013 were analyzed in a multicentre retrospective case series. The rate of progression to invasive vaginal cancer and the potential risk factors were evaluated.
RESULTS: 205 women with biopsy diagnosis of HG-VaIN were considered, with a mean follow up of 57 months (range 4-254 months). 12 cases of progression to vaginal squamocellular cancer were observed (5.8%), with a mean time interval from treatment to progression of 54.6 months (range 4-146 months). The rate of progression was significantly higher in women diagnosed with VaIN3 compared with VaIN2 (15.4% vs. 1.4%, p < 0.0001). Women with HG-VaIN and with previous hysterectomy showed a significantly higher rate of progression to invasive vaginal cancer compared to non-hysterectomised women (16.7% vs. 1.4%, p < 0.0001). A higher risk of progression for women with VaIN3 and for women with previous hysterectomy for cervical HPV-related disease was confirmed by multivariable logistic regression analysis.
CONCLUSIONS: A higher rate of progression to vaginal cancer was reported in women diagnosed with VaIN3 on biopsy and in women with previous hysterectomy for HPV-related cervical disease. These patients should be considered at higher risk, thus a long lasting and accurate follow up is recommended.

Forde GK, Tewari D
Targeted Treatment of a Rare Vaginal Sarcoma With an Anaplastic Lymphoma Kinase Inhibitor.
Obstet Gynecol. 2016; 127(2):222-5 [PubMed] Related Publications
BACKGROUND: Anaplastic lymphoma kinase is a tyrosine kinase receptor that can become oncogenic. Crizotinib is a tyrosine kinase inhibitor that shows activity in patients with anaplastic lymphoma kinase rearrangements that have failed conventional therapies.
CASE: A 34-year-old woman presented with a painful 3-cm left vulvar-vaginal mass, which was excised and determined to be a sarcoma with positive surgical margins. Fluorescence in situ hybridization testing of her tumor was conducted and demonstrated anaplastic lymphoma kinase gene rearrangements. A 3-cm mass recurred 1 month later. Treatment with 250 mg crizotinib orally twice daily resulted in complete regression of all visible or palpable tumor within 3 weeks.
CONCLUSION: Molecular evaluation techniques can be used to direct targeted therapy for select malignancies. Future technologic advances will expand the number of malignancies for which these treatment approaches can be used.

Han K, Viswanathan AN
Brachytherapy in Gynecologic Cancers: Why Is It Underused?
Curr Oncol Rep. 2016; 18(4):26 [PubMed] Related Publications
Despite its established efficacy, brachytherapy is underused in the management of cervical and vaginal cancers in some parts of the world. Possible reasons for the underutilization of brachytherapy include the adoption of less invasive techniques, such as intensity-modulated radiotherapy; reimbursement policies favoring these techniques over brachytherapy; poor physician or patient access to brachytherapy; inadequate maintenance of brachytherapy skills among practicing radiation oncologists; transitioning to high-dose-rate (HDR) brachytherapy with increased time requirements; and insufficient training of radiation oncology residents.

Khan MJ, Massad LS, Kinney W, et al.
A Common Clinical Dilemma: Management of Abnormal Vaginal Cytology and Human Papillomavirus Test Results.
J Low Genit Tract Dis. 2016; 20(2):119-25 [PubMed] Related Publications
OBJECTIVE: Vaginal cancer is an uncommon cancer of the lower genital tract, and standardized screening is not recommended. Risk factors for vaginal cancer include a history of other lower genital tract neoplasia or cancer, smoking, immunosuppression, and exposure to diethylstilbestrol in utero. Although cervical cancer screening after total hysterectomy for benign disease is not recommended, many women inappropriately undergo vaginal cytology and/or human papillomavirus (HPV) tests, and clinicians are faced with managing their abnormal results. Our objectives were to review the literature on vaginal cytology and high-risk HPV (hrHPV) testing and to develop guidance for the management of abnormal vaginal screening tests.
MATERIALS AND METHODS: An electronic search of the PubMed database through 2015 was performed. Articles describing vaginal cytology or vaginal hrHPV testing were reviewed, and diagnostic accuracy of these tests when available was noted.
RESULTS: The available literature was too limited to develop evidence-based recommendations for managing abnormal vaginal cytology and hrHPV screening tests. However, the data did show that (1) the risk of vaginal cancer in women after hysterectomy is extremely low, justifying the recommendation against routine screening, and (2) in women for whom surveillance is recommended, e.g., women posttreatment for cervical precancer or cancer, hrHPV testing may be useful in identification of vaginal cancer precursors.
CONCLUSIONS: Vaginal cancer is rare, and asymptomatic low-risk women should not be screened. An algorithm based on expert opinion is proposed for managing women with abnormal vaginal test results.

Ozgul N, Basaran D, Boyraz G, et al.
Radical Hysterectomy and Total Abdominal Vaginectomy for Primary Vaginal Cancer.
Int J Gynecol Cancer. 2016; 26(3):580-1 [PubMed] Related Publications
The aim of this surgical video is to demonstrate en bloc radical removal of uterus and vagina in a patient with clinical early-stage vaginal cancer. Surgical treatment was offered to our patient for clinical early-stage primary vaginal cancer. An en bloc radical hysterectomy, systematic pelvic lymphadenectomy, and total abdominal vaginectomy were performed. Postoperative adjuvant radiation or chemotherapy was not recommended for completely resected pathologic stage I disease with no lymph node involvement and negative surgical margins. Radical surgery can be a treatment option for selected patients with primary vaginal cancer.

Todo Y, Okamoto K, Suzuki Y, et al.
Radicality of initial surgery for primary malignant melanoma of the vagina.
Melanoma Res. 2016; 26(2):173-80 [PubMed] Related Publications
Radical surgery is considered not to improve the prognosis of primary malignant melanoma of the vagina (PMMV). This study was carried out to review the general consensus. A systematic review was performed on the basis of data from 10 patients in our cohort and 147 patients in the previous literature. The radicality of the initial surgery (RAINS) score was defined as the total number of points in terms of the resected organs. The target organs were the vagina, vulva, urethra, bladder, uterus, anus, rectum, pelvic lymph nodes, and inguinal lymph nodes. Overall survival (OS) according to the RAINS score was analyzed using the Kaplan-Meier method. Information on tumor stage, size, and depth of invasion was not obtained in 15, 47, and 43% of patients, respectively. The median follow-up period was 18 months. OS with a RAINS score of at least 7 was significantly longer than that with a RAINS score of up to 6 (median survival time, 41 vs. 19 months; log-rank test, P=0.037), despite the fact that the former group included significantly more patients with advanced-stage disease. A significant difference in OS was not found between patients with a RAINS score of at least 6 and up to 5. The therapeutic significance of radical surgery for PMMV has not been assessed appropriately in previous studies because of the lack of comparability among groups and differences in the definitions of surgical radicality. Patients with PMMV might benefit from initial surgery with appropriate surgical radicality, despite incomplete validation of the RAINS score.

Lalya I, Maghous A, Marnouche E, et al.
RapidArc for centrally recurrent cervical cancer in the vaginal cuff following primary surgical therapy: a case report.
World J Surg Oncol. 2016; 14(1):21 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Pelvic recurrences of cervical cancer after primary surgical treatment can be potentially cured with radical hysterectomy or chemoradiation therapy. Combined radio-chemotherapy is believed to improve results compared to other option. Currently, RapidArc radiotherapy is considered an excellent technological advance that shows great potential for producing highly conformal doses to treatment volumes.
CASE PRESENTATION: We present a case of a 67-year-old woman with history of early cervical cancer initially treated by radical laparoscopic hysterectomy. More than 5 years later, the patient presented with a central pelvic vaginal cuff recurrence that is histologically confirmed. Salvage radiotherapy using RapidArc with concurrent cisplatin-based chemotherapy was indicated. A high dose of 70 Gy was delivered to the gross recurrent disease with simultaneous integrated boost (SIB) to the subclinical disease and good sparing of organs at risk especially the rectum and sigmoid.
CONCLUSIONS: This case clearly demonstrates a large benefit for salvage RapidArc radiotherapy to central pelvic recurrences of gynecological cancers with an excellent rate of local control and less rate of toxicity.

Zhang J, Chang X, Qi Y, et al.
A retrospective study of 152 women with vaginal intraepithelial neoplasia.
Int J Gynaecol Obstet. 2016; 133(1):80-3 [PubMed] Related Publications
OBJECTIVE: To analyze the clinical characteristics and treatment of women with vaginal intraepithelial neoplasia (VAIN), as well as HPV prevalence in this population.
METHODS: A retrospective review was undertaken of the medical records of women diagnosed with VAIN at a clinic in Shenyang, China, between January 1, 2009, and December 31, 2012.
RESULTS: Of the 152 records reviewed, 69 (45.4%) women had low-grade VAIN (VAIN1) and 83 (54.6%) had high-grade VAIN (VAIN2/3). Among 110 patients with an available HPV status, 97 (88.2%) were positive. The predominant HPV types were HPV16, HPV33, HPV81, HPV53, HPV18, HPV58, and HPV66. Previous hysterectomy was documented in 60 (39.5%) patients. Additionally, 80 (52.6%) patients had no history of dysplasia of the lower genital tract. Of patients with VAIN1, 50 (72.5%) were treated by observation only, 31 (62.0%) of whom regressed spontaneously. Of 66 patients with VAIN2, 38 (57.6%) underwent treatment, 14 (36.8%) of whom experienced recurrence or progression. Of 17 patients with VAIN3, 13 (76.5%) underwent treatment, 5 (38.5%) of whom experienced recurrence or progression.
CONCLUSION: Evaluation of the entire vagina by colposcopy is warranted in each patient with abnormal cervical screening results. The predominant HPV genotypes among patients with VAIN could be used to establish diagnosis program and develop an HPV vaccine.

Robertson NL, Hricak H, Sonoda Y, et al.
The impact of FDG-PET/CT in the management of patients with vulvar and vaginal cancer.
Gynecol Oncol. 2016; 140(3):420-4 [PubMed] Free Access to Full Article Related Publications
OBJECTIVES: To evaluate the changes in prognostic impression and patient management following PET/CT in patients with vulvar and vaginal carcinoma; and to compare PET/CT findings with those of conventional imaging modalities.
METHODS: We summarized prospectively and retrospectively collected data for 50 consecutive patients from our institution that enrolled in the National Oncologic PET Registry and underwent FDG-PET/CT for a suspected or known primary or recurrent vulvar/vaginal cancer.
RESULTS: 54/83 (65%) studies included had a diagnosis of vulvar cancer, and the remaining 29/83 (35%), a diagnosis of vaginal cancer. Following FDG-PET/CT, the physician's prognostic impression changed in 51% of cases. A change in patient management, defined as a change to/from a non-interventional strategy (observation or additional imaging), to/from an interventional strategy (biopsy or treatment), was documented in 36% of studies. The electronic records demonstrated that 95% of the management strategies recorded in the physician questionnaires were implemented as planned. MRI and/or CT were performed within one month of the FDG-PET/CT in 20/83 (24%) and 28/83 (34%) cases, respectively. FDG-PET/CT detected nodes suspicious for metastases on 29/83 (35%) studies performed. MRI and CT detected positive nodes on 6 and 11 studies respectively. Distant metastases were identified in 10 cases imaged with FDG-PET and 5 cases that had additional conventional CT imaging. All suspicious lesions seen on CT were positively identified on PET/CT. In 4 cases, an abnormality identified on PET/CT, was not seen on diagnostic CT.
CONCLUSIONS: FDG-PET/CT may play an important role in the management of vulvar and vaginal carcinoma.

Stefanović A, Jeremić J, Jeremić K, et al.
Primary melanoma of the vagina: a case report and review of literature.
Eur J Gynaecol Oncol. 2015; 36(6):755-7 [PubMed] Related Publications
Summary Primary melanoma of the vagina is a rare and very aggressive tumor with an incidence of only 0.46 per one million women per year and less than 250 cases reported in the literature. Here the authors present a case of a 60-year-old woman, gravida 5, para 5, post-menopausal by 28 years, admitted to the Clinic for Obstetrics and Gynecology, with recurrent vaginal bleeding for the last year and with the complaint of a palpable tumor near the vaginal introitus. The preoperative biopsy revealed melanoma. CT scan did not prove she had distant metastasis. The patient was treated surgically, with wide local excision of four x five cm measured lesion and safety margins of two cm. Bilateral inguinal lymphadenectomy was performed. Follow-up five months after initial diagnosis, revealed no evidence of local recurrency or distant metastasis.

Lee YH, Chong GO, Hong DG
Is gastrointestinal stromal tumor (GIST) originating from the rectovaginal septum GIST or extra-GIST (EGIST)? A case report with literature review.
Eur J Gynaecol Oncol. 2015; 36(6):750-4 [PubMed] Related Publications
Gastrointestinal stromal tumors (GISTs) are rare tumors of the gastrointestinal (GI) tract that arise from primitive mesenchymal cells. Extragastrointestinal stromal tumors (EGISTs) are extremely rare tumors that show the features of GISTs outside the GI tract. Their most common locations are the omentum, mesentery, and retroperitoneum. The authors report herein a case of a 54-year-old woman with GIST in rectovaginal septum. The patient underwent low anterior resection of the rectum, total abdominal hysterectomy, bilateral salpingo-oophorectomy, and partial resection of the posterior vagina. She received adjuvant therapy with an oral tyrosine-kinase inhibitor. She is presently healthy without any evidence of recurrence at 26 months after surgery. For GISTs arising in the rectovaginal septum, it is difficult to ascertain whether the tumor origin site is the rectum, rectovaginal septum, or vagina. In other words, it is difficult to classify these tumors as GISTs or EGISTs. More consideration for the exact origin should be given to the GIST in the rectovaginal septum for the precise diagnosis (GIST or EGIST) and risk classification in future.

Zhou H, Mody RR, Luna E, et al.
Clinical performance of the Food and Drug Administration-Approved high-risk HPV test for the detection of high-grade cervicovaginal lesions.
Cancer Cytopathol. 2016; 124(5):317-23 [PubMed] Related Publications
BACKGROUND: In recent years, high-risk human papillomavirus (hrHPV) testing for triaging atypical squamous cells of undetermined significance and cotesting with cytology have been implemented in clinical practice. However, clinical data for primary screening with human papillomavirus (HPV) testing alone are currently lacking.
METHODS: This study retrospectively reviewed the correlation of cytology, histology, and hrHPV testing through the use of a cytology laboratory quality assurance database with 130,648 Papanicolaou (Pap) tests interpreted at Houston BioReference Laboratories and Houston Methodist Hospital between March 1, 2013 and June 30, 2014. Among the 47,499 patients who had undergone cytology-HPV cotesting, 1654 underwent follow-up biopsies.
RESULTS: The sensitivities of the hrHPV and Pap tests were 80.8% and 81.2%, respectively, for detecting any type of cervicovaginal dysplasia and 91.3% and 90.9%, respectively, for high-grade cervicovaginal lesions. For biopsy-confirmed high-grade cervicovaginal lesions (cervical intraepithelial neoplasia grade 2+, adenocarcinoma in situ, or carcinoma; n = 253), the false-negative rates for hrHPV and Pap tests were 8.7% and 9.1%, respectively. The false-negative rate for cytology-hrHPV cotesting was only 1.2%.
CONCLUSIONS: In clinical practice, the hrHPV test alone is not significantly superior to the Pap test as a primary screening method for cervicovaginal lesions. The false-negative rate of the hrHPV test in detecting biopsy-confirmed high-grade cervicovaginal lesions is comparable to the rate of the Pap test. Women with cytology and hrHPV cotesting, however, have a significantly lower false-negative rate than those undergoing either test alone. Currently, cytology-HPV cotesting remains the best strategy for detecting high-grade cervicovaginal lesions. Cancer Cytopathol 2016;124:317-23. © 2016 American Cancer Society.

Chang JH, Jang WI, Kim YB, et al.
Definitive treatment of primary vaginal cancer with radiotherapy: multi-institutional retrospective study of the Korean Radiation Oncology Group (KROG 12-09).
J Gynecol Oncol. 2016; 27(2):e17 [PubMed] Free Access to Full Article Related Publications
OBJECTIVE: To assess the outcome of the treatment of primary vaginal cancer using definitive radiotherapy (RT) and to evaluate the prognostic factors of survival.
METHODS: The medical records of nine institutions were retrospectively reviewed to find the patients with vaginal cancer treated with definitive RT with or without chemotherapy. A total of 138 patients met the inclusion criteria. None had undergone curative excision.
RESULTS: The median follow-up time of the survivors was 77.6 months and the median survival time was 46.9 months. The 5-year overall survival, cancer-specific survival (CSS), and progression-free survival (PFS) rates were 68%, 80%, and 68.7%, respectively. In the survival analysis, the multivariate analysis showed that a lower the International Federation of Gynecology and Obstetrics (FIGO) stage and prior hysterectomy were favorable prognostic factors of CSS, and a lower FIGO stage and diagnosed prior to year 2000 were favorable prognostic factors of PFS. In the subgroup analysis of the patients with available human papillomavirus (HPV) results (n=27), no statistically significant relationship between the HPV status and recurrence or survival was found. Grade 3 or 4 acute and late toxicity were present in 16 and 9 patients, respectively. The FIGO stage and the tumor size were predictors of severe late toxicity.
CONCLUSION: The data clearly showed that a higher FIGO stage was correlated with a worse survival outcome and higher severe late toxicity. Therefore, precise RT and careful observation are crucial in advanced vaginal cancer. In this study, the HPV status was not related to the survival outcome, but its further investigation is needed.

Murakami N, Norihisa Y, Isohashi F, et al.
Proposed definition of the vaginal cuff and paracolpium clinical target volume in postoperative uterine cervical cancer.
Pract Radiat Oncol. 2016 Jan-Feb; 6(1):5-11 [PubMed] Related Publications
PURPOSE: The aim of this study was to develop an appropriate definition for vaginal cuff and paracolpium clinical target volume (CTV) for postoperative intensity modulated radiation therapy in patients with uterine cervical cancer.
METHODS AND MATERIALS: A working subgroup was organized within the Radiation Therapy Study Group of the Japan Clinical Oncology Group to develop a definition for the postoperative vaginal cuff and paracolpium CTV in December 2013. The group consisted of 5 radiation oncologists who specialized in gynecologic oncology and a gynecologic oncologist. A comprehensive literature review that included anatomy, surgery, and imaging fields was performed and was followed by multiple discreet face-to-face discussions and e-mail messages before a final consensus was reached.
RESULTS: Definitions for the landmark structures in all directions that demarcate the vaginal cuff and paracolpium CTV were decided by consensus agreement of the working group. A table was created that showed boundary structures of the vaginal cuff and paracolpium CTV in each direction.
CONCLUSIONS: A definition of the postoperative cervical cancer vaginal cuff and paracolpium CTV was developed. It is expected that this definition guideline will serve as a template for future radiation therapy clinical trial protocols, especially protocols involving intensity modulated radiation therapy.

Sano T, Uhara H, Mikoshiba Y, et al.
Nivolumab-induced organizing pneumonia in a melanoma patient.
Jpn J Clin Oncol. 2016; 46(3):270-2 [PubMed] Related Publications
We report the case of a 70-year-old woman with vaginal melanoma and multiple metastases in the lung. After the third dose of nivolumab, decreased room-air resting arterial oxygen saturation with bilateral basal fine crackles on auscultation developed despite the absence of respiratory symptoms. Computed tomography showed ground-glass opacities with airspace consolidations scattered with a peculiar distribution, and most were observed around the existing metastatic tumors in the lung. From the 42nd day to the 56th day after the last administration of nivolumab, she received dexamethasone 1-2 mg/body for the prevention of adverse events after stereotactic radiation for brain metastasis. At 3 months after the last administration of nivolumab, a computed tomography scan revealed improvement of the pneumonia and a decreased size and number of metastatic lesions in the lung, although some lesions showed enlargement. Further examination is needed to clarify the relationship between the pattern of pneumonia after Nivo therapy and clinical effects.

Lopes LF, Macedo CR, Aguiar Sdos S, et al.
Lowered Cisplatin Dose and No Bleomycin in the Treatment of Pediatric Germ Cell Tumors: Results of the GCT-99 Protocol From the Brazilian Germ Cell Pediatric Oncology Cooperative Group.
J Clin Oncol. 2016; 34(6):603-10 [PubMed] Related Publications
PURPOSE: We describe the results of a risk-adapted, response-based therapeutic approach from the Brazilian GCT-99 study on germ cell tumors.
PATIENTS AND METHODS: From May 1999 to October 2009, 579 participants were enrolled in the Brazilian GCT-99 study. Treatment, defined as specific chemotherapy regimen and number of cycles, was allocated by means of risk-group assignment at diagnosis with consideration for stage and primary tumor site. Patients at low risk received no chemotherapy. Patients at intermediate risk (IR) with a good response (GR) received four cycles of platinum and etoposide (PE), for total doses of platinum 420 mg/m(2) and etoposide 2,040 mg/m(2). Patients at IR with a partial response (PR) received three cycles of PE plus three cycles of ifosfamide, vinblastine, and bleomycin. Patients at high risk (HR) with a GR received four cycles of PE and ifosfamide (PEI) at total doses of platinum 420 mg/m(2), etoposide 1,200 mg/m(2), and ifosfamide 30 g/m(2). Patients at HR with a PR received six cycles of PEI.
RESULTS: The risk-group distribution was 213 LR, 138 IR, and 129 HR for 480 evaluable patients. Overall survival (OS) and event-free survival (EFS) rates at 10 years were, respectively, 90% and 88.6% in the IR-GR group (n = 126) and 74.1% and 74.1% in the IR-PR group (n = 12). Ten-year rates for the HR-GR group (n = 86) were an OS of 66.8% and an EFS of 62.5%. The HR-PR group (n = 43) had an OS of 74.8% and an EFS of 73.4%. In univariable and multivariable analysis, increased serum lactate dehydrogenase level and histology for a metastatic immature teratoma were prognostic of a worsened outcome.
CONCLUSION: Reduction of therapy to two drugs did not compromise survival outcomes for patients in the IR-GR group, and escalation of therapy with PEI did not significantly improve OS and EFS in patients at HR.

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(5):636-44 [PubMed] Related Publications
Adenocarcinomas exhibiting gastric differentiation represent a recently described and uncommon subtype of non-human papillomavirus (HPV)-related cervical adenocarcinoma. They comprise a spectrum from a well-differentiated variant (adenoma malignum/mucinous variant of minimal deviation adenocarcinoma) to a more poorly differentiated overtly malignant form, generally referred to as gastric-type adenocarcinoma. Rarely, such tumors have also been described as primary vaginal neoplasms. Gastric-type adenocarcinomas exhibit considerable morphologic overlap with adenocarcinomas originating outside the female genital tract, especially mucinous adenocarcinomas arising in the pancreas and biliary tract. Moreover, they often metastasize to unusual sites, such as the ovary and peritoneum/omentum, where they can be mistaken for metastatic adenocarcinomas from other, nongynecologic sites. There is little information regarding the immunophenotype of gastric-type adenocarcinomas, and knowledge of this is important to aid in the distinction from other adenocarcinomas. In this study, we undertook a detailed immunohistochemical analysis of a large series of cervical (n=45) and vaginal (n=2) gastric-type adenocarcinomas. Markers included were cytokeratin (CK)7, CK20, CDX2, carcinoembryonic antigen, CA125, CA19.9, p16, estrogen receptor, progesterone receptor, MUC6, PAX8, PAX2, p53, hepatocyte nuclear factor 1 beta, carbonic anhydrase IX, human epidermal receptor 2 (HER2), and mismatch repair (MMR) proteins. All markers were classified as negative, focal (<50% of tumor cells positive), or diffuse (≥50% tumor cells positive) except for p53 (classified as "wild-type" or "mutation-type"), HER2 (scored using the College of American Pathologists guidelines for gastric carcinomas), and MMR proteins (categorized as retained or lost). There was positive staining with CK7 (47/47-45 diffuse, 2 focal), MUC6 (17/21-6 diffuse, 11 focal), carcinoembryonic antigen (25/31-12 diffuse, 13 focal), carbonic anhydrase IX (20/24-8 diffuse, 12 focal), PAX8 (32/47-20 diffuse, 12 focal), CA125 (36/45-5 diffuse, 31 focal), CA19.9 (11/11-8 diffuse, 3 focal), hepatocyte nuclear factor 1 beta (13/14-12 diffuse, 1 focal), CDX2 (24/47-4 diffuse, 20 focal), CK20 (23/47-6 diffuse, 17 focal), and p16 (18/47-4 diffuse, 14 focal). Most cases were negative with estrogen receptor (29/31), progesterone receptor (10/11), PAX2 (18/19), and HER2 (25/26). p53 showed "wild-type" and "mutation-type" staining in 27 of 46 and 19 of 46 cases, respectively. MMR protein expression was retained in 19 of 20 cases with loss of MSH6 staining in 1 patient with Lynch syndrome. Molecular studies for HPV were undertaken in 2 tumors, which exhibited diffuse "block-type" immunoreactivity with p16, and both were negative. This is the first detailed immunohistochemical study of a large series of gastric-type adenocarcinomas of the lower female genital tract. Our results indicate immunophenotypic overlap with pancreaticobiliary adenocarcinomas but suggest that PAX8 immunoreactivity may be especially useful in distinguishing gastric-type adenocarcinomas from pancreaticobiliary and other nongynecologic adenocarcinomas, which are usually negative. Diffuse "block-type" p16 immunoreactivity in a cervical adenocarcinoma is not necessarily indicative of a high-risk HPV-associated tumor.

Rivard C, Carter JS, Downs LS
Low-grade Endometrial Stromal Sarcoma Primarily Arising in the Vagina: A Case Report.
J Reprod Med. 2015 Sep-Oct; 60(9-10):433-5 [PubMed] Related Publications
BACKGROUND: Endometrial stromal sarcoma (ESS) is a rareform of endometrial cancer, comprising < 0.2% of all uterine malignancies and 10% of all uterine sarcomas. To date, the English-language literature contains 6 reports of extrauterine ESS arising primarily in the vagina. We describe the seventh such case, and the first case in which the origin is at the introitus of the vagina.
CASE: A 43-year-old, nulligravid, Caucasian woman presented for an annual gynecologic examination and was found to have an asymptomatic 5 x 5-mm, rubbery, soft tissue mass at the 5 o'clock position of the vaginal introitus. As has been reported in several cases of low-grade ESS, this case originated at a site of endometriosis.
CONCLUSION: Based on our experience as well as a thorough review of the literature, it appears that early stage low-grade ESS arising in the vagina can be treated effectively with surgical resection followed by close observation for recurrence.

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