Toll-like receptors 7, 8, and 9 expression and function in primary human cervical cancer Langerhans cells: evidence of anergy.

OBJECTIVE: Human papillomavirus oncoproteins E6 and E7 down modulate Toll-like receptor (TLR) 9 expression in infected keratinocytes. We explored the status of expression and function of TLR7, TLR8, and TLR9 in primary human Langerhans cells (LCs) isolated from cervical tumors. METHODOLOGY: Single-cell suspensions were made from fresh tissues of squamous cell carcinoma (International Federation of Gynecology and Obstetrics stage IB2); myeloid dendritic cells were purified using CD1c magnetic activated cell separation kits. Langerhans cells were further flow sorted into CD1a*CD207* cells. Acute monocytic leukemia cell line THP-1-derived LCs (moLCs) formed the controls. mRNA from flow-sorted LCs was reverse transcribed to cDNA and TLR7, TLR8, and TLR9 amplified. Monocyte-derived Langerhans cells and cervical tumor LCs were stimulated with TLR7, TLR8, and TLR9 ligands. Culture supernatants were assayed for interleukin (IL) 1ß, IL-6, IL-10, IL-12p70, interferon (IFN) α, interferon γ, and tumor necrosis factor (TNF) α by Luminex multiplex bead array. Human papillomavirus was genotyped. RESULTS: We have for the first time demonstrated that the acute monocytic leukemia cell line THP-1 can be differentiated into LCs in vitro. Although these moLCs expressed all the 3 TLRs, tumor LCs expressed TLR7 and TLR8, but uniformly lacked TLR9. Also, moLCs secreted IL-6, IL-1ß, and tumor necrosis factor α to TLR8 ligand and interferon α in response to TLR9 ligand; in contrast, tumor LCs did not express any cytokine to any of the 3 TLR ligands. Human papillomavirus type 16 was one of the common human papillomavirus types in all cases. CONCLUSIONS: Cervical tumor LCs lacked TLR9 expression and were functionally anergic to all the 3: TLR7, TLR8, and TLR9 ligands, which may play a crucial role in immune tolerance. The exact location of block(s) in TLR7 and TLR8 signaling needs to be investigated, which would have important immunotherapeutic implications.

Clinico-Pathological Characteristics, Management, and Prognostic Factors of Patients with Uterine Carcinosarcoma: a Retrospective Analysis.

Uterine carcinosarcoma is a rare, highly aggressive, rapidly progressing neoplasm associated with a poor prognosis. It comprises 1-5% of all uterine malignancies but accounts for 16.4% of all deaths caused by uterine malignancies. There is a definite paucity of data available from the Indian subcontinent. Hence, we retrospectively conducted this study to analyze the clinical and pathological characteristics and outcomes of women with uterine carcinosarcoma in the past 10 years managed at the tertiary care center. This is a retrospective study of women with histologically proven uterine carcinosarcoma treated at a tertiary cancer center in South India between August 2009 and April 2019. Inpatient and outpatient records were reviewed; clinicopathological data were collected; and follow-up and survival data were ascertained. Over a period of 10 years, 20 patients were diagnosed with uterine carcinosarcoma. The majority of patients were postmenopausal (80%). Post-menopausal bleeding was the main presenting complaint in about 80% of patients. More than two-thirds of patients presented in the early stage (stage I, 55%; stage II, 20%). All patients underwent staging laparotomy. Patients with good performance status (85%) received adjuvant concurrent chemoradiotherapy and chemotherapy. At a median follow-up of 40 months, 7 (35%) patients were alive, out of which 6 are disease-free and 1 had a recurrence. The event-free survival at a median follow-up of 40 months was 40% and the overall survival was 48.5%. The outcome did not significantly differ based on the age, tumor histology (heterologous versus homologous), stage, and depth of myometrial invasion. Uterine carcinosarcoma, though rare, needs to be recognized as a distinct entity, and treated aggressively. Surgery is the cornerstone of therapy. Adjuvant concurrent chemoradiation and chemotherapy improve local control and may delay recurrence, but have shown little survival advantage. The optimal adjuvant treatment for this uncommon disease is yet to be established, highlighting the need for larger multicentric studies on this tumor.

Lymph Node Metastasis and Patterns of Recurrence in Vulvar Carcinoma: 10 Years' Single Center Experience.

Vulvar carcinoma is a relatively rare malignancy and there is a paucity of data, especially from India and other developing countries regarding the prognostic factors impacting recurrence and survival. A retrospective observational study was conducted in the Department of Gynecologic Oncology at a tertiary care, regional cancer institute, including all patients with carcinoma vulva who underwent surgery between 2009 and 2018. Demographic profile, surgical-pathological information, details of neo-adjuvant chemotherapy, adjuvant radiation and chemotherapy, and peri-operative complications were analyzed. Long-term follow-up data was gathered, with an evaluation of various prognostic factors impacting recurrence and overall survival outcome. Forty-five cases with mean age of 56.2 years (range 29-82) were treated during the study period. Surgery was the initial treatment modality in 41 (91.1%) cases. Neo-adjuvant chemotherapy prior to surgery was given to four cases. After complete surgico-pathological staging, most patients had stage I disease (26 cases, 57.8%) and 22.2% had stage II disease. Owing to microscopic lymph node involvement, seven cases (15.6%) belonged to FIGO stage III disease. Two cases had stage IVA disease with fixed groin nodes. Adjuvant chemotherapy in the form of 5-fluoro uracil and cisplatin was administered to four out of the nine patients with nodal involvement. The remaining five were advised adjuvant groin radiation. At a median follow-up of 34 months (range 2-114 months), 12 cases (26.7%) experienced a recurrence and one case with stage IVA disease progressed during adjuvant chemotherapy. The 5-year overall survival was 76.6% and the 5-year disease-free survival was 69.6%. There were a total number of 10 deaths, of which seven were due to disease recurrence or progression and the remaining 30% of deaths were due to medical co-morbid conditions. Overall survival was negatively impacted by increasing age (age > 60 years), number of positive nodes, presence of perinodal spread, and stage of the disease. Recurrence-free survival was significantly reduced in those with the presence of peri-nodal spread and lympho-vascular space invasion. The incidence of lymph node metastasis was found to be higher in patients with age > 60 years, increasing tumor size, presence of lympho-vascular space invasion and the number of lymph nodes removed. In carcinoma vulva, treatment should be individualized with multidisciplinary cooperation. In our series, we found that the stage of disease, nodal positivity, and nodal positivity with extra-capsular spread were significant prognostic factors impacting survival on analysis. Lymph nodal positivity was associated with increasing tumour size, presence of lympho-vascular invasion, and patient age.

Relationship between lymph node metastases and histopathological parameters in carcinoma cervix: a multivariate analysis.

A retrospective review of 360 cases of carcinoma of the cervix with clinical stage IB and IIA who had undergone radical hysterectomy and pelvic node dissection between 2000 and 2005 was carried out. Lymph node metastasis was present in 79/360 patients (21.9%). LVSI positivity, full thickness stromal invasion, involvement of the uterine isthmus, positive parametrium, positive vaginal margins, involvement of uterine corpus was seen in: 25.3% and 9.2% (p < 0.001); 63% and 32% (p < 0.001); 32.9% and 13.8% (p < 0.001);15.2% and 5% (p < 0.004); 24% and 14.2% (p < 0.005); 17.7% and 13.8% (p = 0.11) of the patients, with and without lymph node metastasis, respectively. The tumour size was <4 cm in 50.6% and 58.3% and >4 cm in 49.3% and 41.6% of the patients, with and without lymph node metastasis, respectively (p = 0.22), which was statistically not significant. In the majority of patients, the histopathology type was squamous cell carcinoma in both the groups. In patients with lymph node metastases 79.7% had grade III tumour as compared with 69.5% in patients without lymph node metastases (p = 0.19). Multiple logistic regression indicated that only lymphovascular space involvement and full thickness stromal invasion were statistically significant (p < 0.001 and p < 0.002, respectively) for lymph node metastasis.

Impact of Optimal Therapy and Prognostic Factors in Malignant Germ Cell Tumors of Ovary: 20 Years' Institutional Experience.

The objective of this study is to analyze the impact of clinicopathological and treatment-related factors on survival in patients with malignant ovarian germ cell tumor. A total of 253 patients of ovarian germ cell malignancy were retrospectively reviewed during 2000-2019. Out of these, 111 had primary treatment at our institute, which is a dedicated regional cancer center. The remaining 142 were operated elsewhere and were referred to us for adjuvant chemotherapy or with recurrent disease. The clinicopathological and treatment-related characteristics were analyzed for association with tumor persistence/recurrence or death. Among them, 107 were dysgerminomas; 60 had endodermal sinus tumor, 53 mixed germ cell tumors, and 31 immature teratoma; and one each had embryoma and primitive germ cell tumor. The median follow-up period was 19 months (range 0-214). Median time to recurrence or progression was 5 months. Forty-nine patients (19.4%) had a recurrence and there were 16 (6.3%) deaths. Five-year disease-free-survival was 71.3% and 5-year overall survival rate was 88.1%, for the entire cohort. Disease-free-survival was 90.4% and overall survival was 92.1% for patients entirely treated at the reporting institute. Sub-group analysis based on treatment adequacy showed that survival rate was 91.0% in patients who had timely and complete initial treatment versus 78.3% in patients where treatment was incomplete or delayed (p = 0.032). Factors affecting relapse were tumor histology, absence of surgical staging, presence of residual disease, inadequate response to chemotherapy, treatment outside reporting institute, and incomplete/delayed chemotherapy. Significant factors adversely affecting survival were presence of post-operative residual disease, tumor histology, incomplete response to chemotherapy, and inadequate/delayed treatment at primary setting. There was no statistically significant difference based on disease stage and whether fertility-sparing surgery or non-fertility-sparing surgery was performed. Prognosis of ovarian germ cell malignancies is excellent with timely, optimal treatment. The outcome improves significantly if managed adequately in the primary setting, involving dedicated gynecologic oncologists.

Oestrogen Receptor-α binds the FOXP3 promoter and modulates regulatory T-cell function in human cervical cancer.

Oestrogen controls Foxp3 expression in regulatory T cells (Treg cells) via a mechanism thought to involve oestrogen receptor alpha (ERα), but the molecular basis and functional impact of ERα signalling in Treg cells remain unclear. We report that ERα ligand oestradiol (E2) is significantly increased in human cervical cancer (CxCa) tissues and tumour-infiltrating Treg cells (CD4+CD25hiCD127low), whereas blocking ERα with the antagonist ICI 182,780 abolishes FOXP3 expression and impairs the function of CxCa infiltrating Treg cells. Using a novel approach of co-immunoprecipitation with antibodies to E2 for capture, we identified binding of E2:ERα complexes to FOXP3 protein in CxCa-derived Treg cells. Chromatin immunoprecipitation analyses of male blood Treg cells revealed ERα occupancy at the FOXP3 promoter and conserved non-coding DNA elements 2 and 3. Accordingly, computational analyses of the enriched regions uncovered eight putative oestrogen response elements predicted to form a loop that can activate the FOXP3 promoter. Together, these data suggest that E2-mediated ERα signalling is critical for the sustenance of FOXP3 expression and Treg cell function in human CxCa via direct interaction of ERα with FOXP3 promoter. Overall, our work gives a molecular insight into ERα signalling and highlights a fundamental role of E2 in controlling human Treg cell physiology.

A review of squamous cell carcinoma arising in mature cystic teratoma of the ovary.

INTRODUCTION: Germ cell tumors account for 20-25% of ovarian neoplasms. Mature cystic teratoma (MCT) is the most common ovarian germ cell tumor. Malignancy in MCT is seen in 1-2% of the cases. Squamous cell carcinoma (SCC) accounts for 80% of the cases and carries a poor prognosis. AIM: To study the clinicopathological factors, management protocols and its outcome. MATERIALS AND METHODS: Case records reviewed from August 2006 to August 2011 at our institute identified 10 women with SCC in ovarian MCT. Staging was done according to FIGO 2009 guidelines. Primary surgery followed by adjuvant treatment with platinum based chemotherapy was given. RESULTS: Median age was 53.5 years. Six out of 10 patients were postmenopausal and aged above 50 years. Abdominal pain and abdominal mass were the most common presenting symptoms. According to FIGO: Two in stage 1, five in stage 2, two in stage 3 and one in stage 4. Among six optimally cytoreduced patients, five (83%) had no evidence of disease with a median follow up of 10 months. Whereas all four (100%) suboptimally cytoreduced patients had progressive disease within 3 to 4 months of primary surgery despite chemotherapy. CONCLUSION: Squamous cell carcinoma in MCT of ovary is a rarity. It carries a poor prognosis, especially in advanced stages and suboptimally cytoreduced patients. Platinum with or without taxane based chemotherapy may be useful as adjuvant treatment. However, further studies and standardization of treatment protocols are required for any recommendations.

A retrospective clinicopathological study of 131 cases with endometrial cancers--is it possible to define the role of retroperitoneal lymphadenectomy in low-resource settings?

AIM: The study objectives were evaluation of clinicopathological characteristics, correlations between the preoperative and postoperative tumor grades, and their implications on lymph node metastasis. MATERIALS AND METHODS: We conducted a retrospective descriptive study of 131 cases of endometrial cancer examined and treated at a tertiary regional cancer institute between the years 2003 and 2009. We reviewed the oncology database as well as the clinical records and surgico-pathological registry of all these patients. Statistical Methods Used: All the summary measure computation and Chi-square test for comparing more than one proportion was done in spreadsheet (Excel). RESULTS: The multiparity association with endometrial cancer was commonly seen 113/131 (86.2%). Twelve (9.7%) patients preoperatively diagnosed as Grade 1 tumors upgraded to Grade 3 changes in postoperative specimens and six of these 12 patients (50%) had lymph node metastasis. A total of 14/131 (10.6%) cases had lymph nodes metastasis. CONCLUSIONS: There is a poor correlation between the preoperative and the postoperative tumor grades. Routine pelvic lymphadenectomy may be a valuable method in low-risk cases and para-aortic lymphadenectomy may be limited to high-risk endometrial cancers.

Colposcopy: gynecological vision in viewing oral lesions.

CONTEXT: The diagnosis of malignant and potentially malignant epithelial lesions of the oral mucosa cannot be based solely on clinical findings. The histologic evaluation of a representative biopsy specimen thus becomes necessary. The site for biopsy however is always a subjective choice that sometimes raises doubts about its representativeness. So far, no simple and reliable method is available for the selection of the most appropriate area for biopsy. Colposcopy is helpful in the selection of these sites of epithelial dysplasia depending upon the vascular patterns. AIMS: This study was planned to assess the role of Colposcopic examination in the selection of biopsy site in patients with varying grades of oral epithelial dysplasia at various sites. SETTINGS AND DESIGN: One hundred and eighty patients between the ages of 30 and 60 years clinically diagnosed with leukoplakia and carcinoma buccal mucosa were included in the study. MATERIALS AND METHODS: For each of the subjects, a thorough clinical examination followed by Colposcopic assessment was carried out for the selection of biopsy site from the involved mucosa. The histopathological findings were then compared in the two cases and results analyzed. STATISTICAL ANALYSIS USED: The statistical analysis was performed using a paired t-test. RESULTS: In our study, sensitivity and specificity for the selection of biopsy site by Colposcopic examination was found to be higher for leukoplakia than for carcinoma buccal mucosa. CONCLUSIONS: It was concluded that Colposcopic examination was found to be significant in the selection of biopsy site for leukoplakia while clinical criterion was found to be more appropriate for carcinoma buccal mucosa cases.

Accuracy rate of frozen section studies in ovarian cancers: a regional cancer institute experience.

BACKGROUND: Frozen section is a valuable diagnostic procedure in the categorization of ovarian tumors as benign, borderline and malignant. Thus, it guides in tailoring surgical therapy, particularly in young women. AIM: This study was undertaken to determine the accuracy of frozen section in ovarian neoplasms. MATERIALS AND METHODS: A retrospective analysis was done of intraoperative frozen sections for suspected ovarian neoplasms. The frozen and permanent section reports were compared and overall accuracy, sensitivity, specificity, positive and negative predictive values were determined. RESULTS: The study included 135 patients and the overall accuracy of frozen section in determining malignancy was 84.25%. Twenty cases were incorrectly diagnosed, of which 16 cases were under-diagnosed and four were over-diagnosed. With respect to malignant potential, the sensitivity for malignant tumors was highest (91.5%) with specificity of 98.2%. For benign tumors, the sensitivity and specificity were 90.4% and 82.6%, respectively. Borderline tumors had the lowest sensitivity of 31.2% with specificity of 94%. Sensitivity for benign, borderline and malignant tumors in the non-mucinous group was 91.3%, 60% and 95% respectively, whereas the sensitivity was 75%, 18% and 57%, respectively, for mucinous tumors revealing low sensitivity in borderline, mucinous tumors. The low sensitivity rates were due to restriction in the sampling of an adequate number of bits in the large sized tumors. CONCLUSION: The present study concurs that frozen section is an accurate test for diagnosis of benign and malignant tumors. However, accuracy rates for borderline and mucinous tumors are low.

The role of surgery in locally advanced carcinoma of cervix after sub-optimal chemoradiation: Indian scenario.

BACKGROUND: Standard treatment of advanced cervical cancer is concurrent chemoradiation. Radical radiotherapy for carcinoma cervix includes pelvic external beam radiotherapy (EBRT) with the concomitant platinum based chemotherapy followed by intracavitary brachytherapy (ICBT) to boost central disease. Management of patients who are suboptimally treated, especially, after unsuccessful ICBT insertion is not well-defined. This study explores the role of hysterectomy in these patients. MATERIALS AND METHODS: From January 2006 to December 2011, 38 patients with locally advanced cervical cancer, in whom ICBT insertion was unsuccessful, were analyzed retrospectively. Operable patients with no parametrial involvement underwent hysterectomy and outcomes (recurrence free and overall survival) were noted. RESULTS: The major complications in post operative period were wound infection, paralytic ileus and bladder atony all of which were conservatively managed with no mortality. At median follow-up of 36 months (range 12-60 months) there was no recurrence in patients with stage 1B2 and stage IIA, 25 out of 38 (65.8%) were event free and the overall survival was 71%. CONCLUSION: Many patients in Indian scenario receive suboptimal therapy in locally advanced cervical cancer. EBRT with chemotherapy followed by type 1 extra-fascial hysterectomy can be a good alternative for these patients.

Pure large cell neuroendocrine carcinoma of ovary: a rare clinical entity and review of literature.

Large cell neuroendocrine carcinoma (LCNEC) of the ovary is a rare tumor and is now included in the World Health Organization tumor classification. Its prognosis is generally very poor even when the diagnosis is made at an early stage. We report a case of pure large cell neuroendocrine tumour of ovary, appearing 9 months following laparoscopic type I hysterectomy, bilateral pelvic lymph node dissection with ovarian preservation of anatomically normal looking ovaries performed for a cervical biopsy diagnosis of cervical intraepithelial neoplasia grade III with foci of invasion. The rarity lies in the rapid onset (9 months) of a large tumor following conservation of an anatomically normal ovaries. Surgical debulking and five cycles of chemotherapy (Etoposide and Cisplatin) were administered to the woman. She is on followup with no clinical or radiological evidence of disease recurrence for 6 months.

MCM immunocytochemistry as a first line cervical screening test in developing countries: a prospective cohort study in a regional cancer centre in India.

Cervical screening is not available for the majority of women in resource-poor countries. An important factor is a lack of skilled operators necessary for high-throughput assessment of the Papanicolaou (Pap) test currently in use. We compared the efficacy of immunocytochemistry for minichromosome maintenance (MCM) proteins vs standard Pap testing at detecting disease in 455 cervical smears processed in a typical Indian screening laboratory. Conventional (non-monolayer) smears were stained manually and then examined by a cytotechnologist and a cytopathologist. The MCM test was called positive when immunolabelled cells were identified as dyskaryotic by the Pap counterstain. The MCM test was read more quickly than the Pap test (approximately 2 vs 10 min) and there was 100% inter-observer agreement compared with 85% for Pap (P<0.0001). The MCM test detected 10 biopsy-proven cancers or pre-cancers that were not detected by Pap (P=0.002; P=0.016 excluding three cases where the Pap was deemed unsatisfactory on review). The cases in question included one recurrent squamous carcinoma and one adenocarcinoma in a screening patient who would have returned to 5 year recall. There were no false positive MCM test results. We propose that MCM immunocytochemistry has considerable advantages for cervical screening in developing countries like India.

Correlation of endometrial ultrasonography and endometrial histopathology in patients with postmenopausal bleeding.

A retrospective study of 49 cases with persistent postmenopausal vaginal bleeding undergoing hysterectomy in the absence of postoperatively evident diagnosis of genital malignancy was carried out. Normal endometrium was the source of bleeding in 24 cases (48.9%) while 11 cases (22.4%) had evidence of endometritis. Endometrial hyperplasia and polyps were present in 12 cases (24.4%). Two cases were found to have malignancy in the surgical specimen, which were not evident on pre-operative endometrial biopsy. However, there was high degree of suspicion of malignancy in these 2 cases based on the endometrial histopathology and ultrasonographic endometrial thickness. By careful correlation of clinical findings, endometrial histopathology and ultrasound measurement of endometrial thickness, most cases with postmenopausal bleeding can be managed conservatively.

Closed suction drainage versus no drainage following pelvic lymphadenectomy for gynecological malignancies.

The present study was undertaken in the Department of Gynecologic Oncology, Kidwai Memorial Institute of Oncology, Bangalore between October 1998 and July 1999. One hundred and forty three consecutive patients with various gynecological malignancies undergoing pelvic +/- aorto-caval lymphadenectomy as part of definitive surgical procedures, were analyzed. Sixty nine patients had closed suction retroperitoneal pelvic drainage (Group A) and 74 patients had no suction drainage and no pelvic reperitonealization (Group B). The mean postoperative hospitalization was 10 days in both groups. Six patients in Group A and four patients in Group B developed paralytic ileus which responded to conservative line of management. Five patients in Group A and two patients in Group B developed lymphocysts (P > 0.05). The present study demonstrates that closed suction retroperitoneal pelvic drainage following pelvic + aorto-caval lymphadenectomy confers no advantage over no drainage & no pelvic reperitonealization. The partial closure of pelvic peritoneum with no drainage was associated with increased lymphocyst formation (7/25 cases, 28%) during the period immediately before this modified study was undertaken.

Germ cell tumors of the ovary: is there a role for aggressive cytoreductive surgery for nondysgerminomatous tumors?

Thirty-three patients with germ cell tumor of the ovary were seen at Kidwai Memorial Institute of Oncology (KMIO), Bangalore, between 1996 and 1999. Twelve patients had endodermal sinus tumor (EST), 11 dysgerminoma, seven mixed germ cell tumor, and three immature teratoma. Thirteen patients had bulky residual disease of >10 cm after the primary surgery. All but one patient received a combination of bleomycin, etoposide, and cisplatin (BEP) either as neoadjuvant (NACT, 3 cases) or as adjuvant therapy (28 cases). In the present study, all 11 patients with dysgerminoma achieved sustained complete remission (CR), irrespective of the size of residual disease at the time of chemotherapy. Four out of six cases (66.6%) with bulky nondysgerminomatous tumor achieved CR, which was sustained in three cases and one recurred. Fifteen of the remaining 16 (93.7%) nonbulky, nondysgerminomatous tumors achieved CR, which was sustained in 14 cases and recurred in one. This study indicates that there may be a role for aggressive cytoreductive surgery, either primary/interval or at the time of second-look laparotomy, in selected patients with nondysgerminomatous germ cell tumor of the ovary.

Carcinoma of the vulva: a retrospective review of 37 cases at a regional cancer centre in South India.

A retrospective review of 37 cases of carcinoma of the vulva presenting between 1996 and 2000 has been carried out. Thirty-three cases were managed with curative intent and four cases with advanced loco-regional disease were managed with palliative intent. The surgical treatment consisted of wide excision in one case, radical vulvectomy (RV) in six cases, radical vulvectomy and bilateral groin node dissection (RV+BGND) in 25 cases and radical vulvectomy and unilateral groin node dissection in one case. Nine of these 33 women also received adjuvant chemotherapy preoperatively in the hope of achieving better tumour-free surgical margins. Eight cases had a partial response and one case achieved complete response; the surgical margins were free in all these patients. One case received neoadjuvant radiotherapy to the vulva and pelvis followed by RV+BGND, which revealed no residual tumour. Overall, 26/33 cases had groin/inguinal node dissection and 23 (88.4%) of them had groin wound dehiscence. Thirteen of these 26 patients (50%) had inguinal node metastases (Stage III, four patients; Stage IV, nine patients). All the patients with negative nodes were free of disease while three of four patients with Stage III and two of nine patients with Stage IV with nodal metastases remained free of disease. The only patient with Stage III disease plus inguinal node metastases who recurred had multiple positive nodes with extracapsular spread. It appears that although bilateral involvement of the inguinal lymph nodes carries a worse prognosis, unilateral involvement with or without vaginal involvement carries an excellent prognosis provided multiple nodes are not involved. The role of neoadjuvant chemotherapy as compared to neoadjuvant radiotherapy, in locally advanced tumours, needs to be explored further.