HPV genotyping in neuroendocrine carcinoma of the uterine cervix in northern Thailand

Objective

To determine the distribution of HPV genotypes in cervical neuroendocrine carcinoma (NECA) in northern Thailand, and evaluate the correlation between HPV genotype and clinicopathologic features.

Methods

Samples from 111 women treated for cervical NECA at Chiang Mai University Hospital between 1992 and 2009 were tested for HPV genotype. Samples were formaldehyde-fixed, paraffin-embedded, and tested via nested PCR and dot blot hybridization.

Results

Ninety-seven of the 111 samples were adequate for DNA analysis. HPV DNA was detected in 93 samples, of which 76 (81.7%) were single, 14 (15.1%) were multiple, and 3 (3.2%) were untyped infections. HPV18 was the most common subtype (70 cases, 75.3%), followed by HPV16 (28 cases, 30.1%). Other genotypes included HPV58 (3.2%), HPV52 (2.1%), and HPV33 (1.1%). Collectively, HPV16 and/or HPV18 were found in 83 cases (89.3%). Women with HPV18 infection were significantly younger (42.0 years) than those with non-HPV18 infections (54.1 years) (P = 0.003). Associated adenocarcinoma in situ was more frequently seen among women with HPV18 infection (P = 0.034).

Conclusions

HPV18 infection was predominant in cervical NECA. Variations in HPV genotype may be related to the clinicopathologic features and pathogenetic pathways of NECA. Vaccination against HPV16 and HPV18 might provide protection against cervical NECA in almost 90% of cases.     

Human papillomavirus type 18 DNA sequences in adenocarcinoma and adenosquamous carcinoma of the uterine cervix

Human papillomavirus (HPV) DNA sequences were detected by Southern blot hybridization and polymerase chain reaction (PCR) in 10 out of 19 patients (52.7%) with adenocarcinoma [15] and adenosquamous [4] carcinoma of the uterine cervix. HPV 18 DNA was detected in 8 of these 19 patients (42.1%), HPV 16 DNA in 1 patient (5.3%) and HPV type X (unknown) in another (5.3%). Of the 10 HPV positive samples HPV 18 was found in 6 out of 6 pure adenocarcinomas (100%), and in 2 of 4 (50%) adenosquamous carcinomas. HPV 16 and HPV X were each detected in 1 out of 4 (25%) adenosquamous carcinomas. The physical state of the viral DNA was investigated in 5 of the 10 HPV-positive cases. All the specimens from these 5 cases showed HPV to be integrated into the host genome, except for one adenosquamous specimen, which showed both episomal and integrated forms of HPV 16. Six of 8 HPV 18 DNA positive specimens were from cases of pure adenocarcinoma and it was found by PCR that five of these 6 specimens retained fragments of E6/E7, LCR/E7 and early sequence of E1 fragment (sequence: 1188–1373) but deleted most part of E1.     

HPV genotyping in cervical cancer in Northern Thailand: adapting the linear array HPV assay for use on paraffin-embedded tissue

ObjectiveThe objective of this study was to review our experience with abdominal radical trachelectomy in patients with early-stage cervical cancer.MethodsWe performed a retrospective review of all patients who underwent an abdominal radical trachelectomy at the Instituto de Cancerologia—Clinica las Americas in Medellin, Colombia, between April 2002 and January 2008. Data collected included age, stage, histopathologic subtype, tumor size, evidence of lymph-vascular space invasion, estimated blood loss, number of perioperative blood transfusions, number and disease status of lymph nodes removed, disease status of surgical specimen, length of hospital stay, intraoperative and postoperative complications, follow-up time, and fertility outcomes.ResultsFifteen patients underwent an abdominal radical trachelectomy during the study period. The median patient age was 30 years (range, 25–38). Three patients had stage IA2 and 12 had stage IB1 cervical cancer. Eleven patients had squamous cell carcinoma and 4 had adenocarcinoma. Thirteen patients were diagnosed by cervical conization and 2 by colposcopically directed biopsy. All patients had tumors smaller than 2 cm. The median estimated blood loss was 400 ml (range, 200–1000). The median surgical time was 265 min (range, 210–330). The median number of units of packed red blood cells transfused per patient was 2. The median number of lymph nodes removed was 26 (range, 11–48). The median length of hospitalization was 3 days (range, 2–7). The median follow-up time was 32 months (range, 5–32). There was 1 intraoperative complication and 6 postoperative complications in 4 patients. No patient has had a recurrence. Three patients were able to conceive spontaneously; 1 delivered at 31 weeks' gestation, and 2 delivered at term.ConclusionAbdominal radical trachelectomy is feasible and can be performed safely in a developing country in well-selected patients with early cervical cancer who wish to preserve their fertility.     

The role of loop electrosurgical excisional procedure in the management of adenocarcinoma in situ of the uterine cervix

Objectives

To evaluate the occurrence of residual or recurrent disease after loop electrosurgical excisional procedure (LEEP) for adenocarcinoma in situ (AIS) of the uterine cervix.

Study design

Records of 78 patients with a histological diagnosis of AIS of uterine cervix on LEEP who were treated and followed at our center between 1992 and 2008 were, retrospectively, reviewed.

Results

Of 78 patients who underwent LEEP, 47 had negative and 31 had positive resection margins. Of the 47 patients with negative margins, 30 underwent subsequent hysterectomy and residual AIS, including 1 invasive adenocarcinoma, was present in 17% (5/30) of patients. The remaining 17 had no additional procedures. Of the 31 patients with positive margins, 29 patients underwent subsequent hysterectomy and residual AIS, including 4 invasive adenocarcinomas, was present in 48% (14/29) of patients. The remaining two had no additional procedures. After a mean follow-up time of 28 months (range, 1–74 months), no recurrences were observed among the 19 patients who did not undergo hysterectomy.

Conclusions

The incidence of residual disease in patients with negative margins after LEEP for AIS of the uterine cervix is low but not negligible. Therefore, conservative management in these patients seems to be feasible but careful surveillance is required. However, positive resection margin carries a higher risk for residual AIS or occult invasive adenocarcinoma, warranting additional LEEP or hysterectomy in these patients.     

Platelet-derived endothelial cell growth factor as a prognostic factor for radiotherapy outcome in patients with adenocarcinoma of the uterine cervix

OBJECTIVE: The aim of this study was to evaluate the platelet-derived endothelial cell growth factor (PD-ECGF) and VEGF expressions of tumor cells as prognostic factors for radiotherapy outcome in patients with adenocarcinoma of the uterine cervix. METHODS: In 47 formalin fixed, paraffin-embedded tissues from adenocarcinoma of the uterine cervix which had been treated with radiation (1970-1995), PD-ECGF and VEGF expressions were determined using immunohistochemistry, and the relationships between PD-ECGF or VEGF expressions and local control or survival were assessed. RESULTS: PD-ECGF and VEGF expressions were successfully detected in the cytoplasm and/or nucleus of adenocarcinoma cells of the uterine cervix. Of the 47 patients, 44.6 (21/47 cases) and 57.4% (27/47 cases) were positive for PD-ECGF and VEGF, respectively. There was no correlation between PD-ECGF or VEGF expressions and age, grade, or histologic subtypes. Stage and high expression of PD-ECGF showed a significant correlation to local control (P = 0.0025, P = 0.0057, respectively) and were significant independent prognostic factors for 5-year survival in multivariate analysis (P = 0.0039, P = 0.0032, respectively). CONCLUSION: This study demonstrated that PD-ECGF expression was a significant prognostic factor for radiotherapy outcome in patients with adenocarcinoma of the uterine cervix. Preradiation assessment of PD-ECGF expression may be helpful in selecting high-risk patients, providing them with opportunities to receive more sophisticated and individualized treatments.     

Angiogenesis in the uterine cervix

Abstract. Abulafia O, Sherer DM. Angiogenesis in the uterine cervix.
Our objective was to present current data pertaining to angiogenesis of the uterine cervix. We conducted a computerized search to identify relevant studies published in the English language literature. MEDLINE, Current Contents and Index Medicus were searched utilizing the terms: angiogenesis, uterine cervix, intraepithelial neoplasia, squamous cell carcinoma, and adenocarcinoma, from 1966 through June 1999. In contrast to the cyclic phases of the menstrual cycle of the ovary and endometrium in which angiogenesis plays a significant physiologic role, angiogenesis in the uterine cervix is involved primarily in neoplastic processes. These include intraepithelial disease, human papilloma-related disease, and microinvasive and invasive squamous cell and adenocarcinoma of the cervix. In invasive squamous cell and adenocarcinoma of the uterine cervix, angiogenesis appears to be a prognostic indicator for overall survival and disease-free survival. Initial trial studies with anti-angiogenic (angio-inhibitor) therapy such as TNP-470 have been reported and concurrent antitumor activity observed in a limited number of patients with advanced (inoperable or metastatic) disease.     

Prognostic factors of the uterine cervix adenocarcinoma

Background: Prognosis factors for adenocarcinoma of the uterine cervix after primary treatment are poorly established. Methods: A retrospective study of 45 cases of adenocarcinoma of the cervix with a follow-up of 96 months on average was performed. The primary treatment consisted in combined radical surgery and radiotherapy for stage I-II patients while patients with advanced disease were treated by radiotherapy. In case of poor prognosis factors, they were given chemotherapy. Survival rates were established and prognosis factors influencing survival and recurrences were studied. Results: Fifteen women remained alive without evolutive disease. FIGO stage and pelvic node involvement were the most important parameters influencing overall survival. Local failures (27%, average period of 30 months) were unpredictable and led to a dramatic outcome. Histological grade and pelvic node status were significant predictive factors for metastatic recurrence (40%, average period of 29 months). Conclusions: Local recurrence and metastatic dissemination of cervical adenocarcinoma after primary treatment prove to be rapidly fatal although life expectancy can be prolonged with adjuvant treatment of the recurrence. In the event of aggressive tumors with high histological grade and pelvic node involvement, an attempt to assess adjuvant systemic chemotherapy could be useful.     

Adenocarcinoma of the uterine cervix metastatic to lymph nodes

OBJECTIVE: We set out to evaluate the prognostic factors in cervical adenocarcinoma metastatic to lymph nodes. STUDY DESIGN: We performed a retrospective review of 40 patients with cervical adenocarcinoma and lymph node metastasis from 1976 to 1996. RESULTS: Thirty-four patients had adenocarcinoma, and six had adenosquamous carcinoma. Median survival was 50 months. The median survival for patients with stage I disease was 69 months. Stage at diagnosis, treatment with radical hysterectomy, and receiving adjuvant therapy were associated with prolonged survival. A trend toward improved survival was noted with the use of concurrent radiation and chemotherapy as an adjuvant therapy. CONCLUSIONS: Adenocarcinoma metastatic to the lymph nodes does not have a uniformly poor prognosis, especially with early-stage disease. Improved survival was observed with the use of adjuvant therapy, specifically the use of combined chemotherapy and radiation after radical hysterectomy. The optimal therapy in this setting is yet to be determined. (Am J Obstet Gynecol 1998;178:1131-7.)     

人乳头瘤病毒检测及分型基因芯片制备的初步研究

目的开发研制对人乳头瘤病毒(HPV)进行检测及分型的基因芯片。方法2003年6月至2003年12月郑州大学第二附属医院将人工合成的HPV通用探针,HPV6,11,16,18特异性寡核苷酸片段作为实验组探针,将与HPV没有同源性的植物基因片段作为内参照基因点样于玻片介质,制成HPV检测及分型芯片,将HPV标准品荧光标记后与芯片杂交,用GMS418扫描仪对芯片进行扫描,以HPV标准品与芯片的杂交结果对芯片检测方法的准确性进行评价。结果该芯片的内参照结果能做到绝对阳性和绝对阴性,各HPV标准品的芯片检测结果显示其在芯片上的相应位置为明显的阳性信号,且各型别之间无错配杂交信号。结论本研究制作的HPV检测及分型芯片可以成功用于HPV的检测及分型,可望用于临床。     

Surface characteristics of adenocarcinoma of the uterine cervix

The purpose of this study was to analyze the development and classification of cervical adenocarcinoma as seen by scanning electron microscopy (SEM) and correlate the result to morphological alterations in cervical squamous cell carcinoma and endometrial adenocarcinoma. The results showed the endocervical area to be covered by a single layer of columnar cells, some with cilia, containing numerous folds and clefts, but no real glandular structures. The surface of malignant tumors consisted of pavelike arrangements of grooves and clefts covered with blunt microvillous processes, shorter and less delicate than those found on normal columnar cells. The surface microridges of squamous cells were replaced by irregular projections in squamous malignancy and endometrial adenocarcinoma showed a more undulating endometrial appearance.     

Primary hepatoid adenocarcinoma of the uterine cervix

Hepatoid adenocarcinoma is characterized histologically by neoplastic epithelial cells that resemble hepatocellular carcinoma (HCC) and produce alpha-fetoprotein (AFP). We describe a case of hepatoid adenocarcinoma of the uterus that, unlike any other previously reported case, was strictly confined to the cervix. A cervical biopsy demonstrated poorly differentiated adenocarcinoma, and hysterectomy and bilateral salpingo-oophorectomy were subsequently performed. Histologically, the lesion consisted of solid sheets of hepatoid cells accompanied with areas of endometroid adenocarcinoma. The tumor cells showed strong and diffuse cytoplasmic immunoreactivity with AFP in both medullary and adenocarcinoma components. Metastases to bilateral pelvic lymph nodes were detected 12 months after surgery. Since undergoing total pelvic irradiation, the patient has been alive and in full remission for 22 months. To our knowledge, this is the first report of primary hepatoid adenocarcinoma of the uterine cervix.     

Density and distribution of Langerhans cells in the human uterine cervix

Summary Using a combination of immunohistochemistry and planimetric observation we report the density and distribution of Langerhans cells (LCs) in epithelium from the normal ectocervix and from the normal transformation zone (TZ). The density of LCs increased towards the basement membrane. Dendritic LCs aspect was more prominent in the superficial layers.     

Minimal deviation adenocarcinoma of the uterine cervix

Background

Precise preoperative diagnosis of minimal deviation adenocarcinoma (MDA) of the uterine cervix is often difficult because the histological features of MDA closely resemble those of normal cervical glands.

Objective

To review the developments in the diagnosis and treatment of MDA over the past 35 years.

Search strategy

We performed a meta-analysis of all case reports published in the English and Chinese languages between 1975 and 2009 that included a histopathologic diagnosis of MDA. Pooled odds ratios and 95% CIs were calculated for comparisons and analyzed.

Results

The histopathologic diagnosis of MDA remains difficult and is currently based on antigen detection by immunohistochemistry. Cytologic assessment and routine biopsy have low detection rates for MDA. Cross-sectional imaging techniques are helpful but a deep cervical biopsy or cervical conization is necessary for a definitive diagnosis. The mean survival is about 5 years for patients with stage I, 38.1 months for patients with stage II, 22.8 months for patients with stage III, and 5.4 months for patients with stage IV MDA.

Conclusion

Early diagnosis and treatment are key to improving prognosis and survival in patients with MDA.     

Human papillomavirus-positive well-differentiated villoglandular adenocarcinoma of the uterine cervix: A case report and review of the literature

OBJECTIVE: A case of well-differentiated villoglandular adenocarcinoma of the uterine cervix, which was positive for human papillomavirus type 18, was reported. METHODS: The patient was a 52-year-old multipara who was referred to our department because of an abnormal Papanicolaou smear. A 4.0-cm exophytic lesion involving the cervix was detected. She was staged as FIGO IIa and radical hysterectomy combined with bilateral pelvic lymphadenectomy was performed. In addition to histopathological examination of the resected tumor, immunohistochemical studies of estrogen and progesterone receptors were performed using monoclonal antibodies. Detection of human papillomavirus DNA was attempted by polymerase chain reaction using consensus primers. RESULTS: The tumor was a typical well-differentiated villoglandular adenocarcinoma involving the vaginal wall. Both estrogen and progesterone receptors were negative. Human papillomavirus type 18 DNA was detected in the resected tumor. CONCLUSION:'This is the first report of a case of typical well-differentiated villoglandular adenocarcinoma which was positive for human papillomavirus.     

Discovery rate of dysplasia and carcinoma of the uterine cervix in an urban Medical Center serving patients at high risk

File analysis based on 98,970 Pap tests on 58,053 patients from the Martland Medical Center of CMDNJ and its clinics was performed. Discovery rates, period prevalence and incidence rates were calculated for categories of mild to moderate dysplasia through invasive carcinoma. An incidence rate of 27/100,000 for invasive carcinoma was obtained, which is lower than the national average. Period prevalence and incidence rates of dysplasias are both high and similar. This indicates that epidemiologic parameters may need to be studied further. The mean age for the mild to moderate dysplasia was 25.7 years, for moderate to severe dysplasia, 29.29 years and for CIS, 33.25 years. These data may imply that younger women, especially in the urban areas, are at much higher risk than previously expected.     

Asymptomatic vasculitis of the uterine cervix in presence of cervical intraepithelial neoplasia grade III

Case report A 34-year-old woman was diagnosed to have a high-grade cervical intraepithelial neoplasia and was treated by large loop excision of the transformation zone. Histology of the excised cone confirmed the diagnosis but also showed evidence of vasculitis of medium-sized vessels of the cervix. The woman was referred to a physician to rule out underlying systemic disease. Extensive laboratory and clinical screening was negative.Discussion The clinical significance and management of asymptomatic isolated vasculitis of the uterine cervix are discussed.     

Simultaneous squamous carcinoma involving the fallopian tube and the uterine cervix

INTRODUCTION: Primary fallopian tube carcinoma are extremely rare and are most commonly of serous or endometrioid type. Primary squamous cell carcinomas are exceptional with only three cases reported in the English literature. MATERIALS AND METHODS: We present the case of a 43-year-old woman operated for cervical carcinoma. RESULTS: Histologic examination, showed a squamous cell carcinoma of cervix with post operative discovery of a concomitant microinvasive squamous carcinoma of fallopian tube developing on high grade dysplasia and in situ carcinoma lesions. CONCLUSION: Clinico-pathological features of fallopian tube carcinoma, in general, and squamous carcinoma, in particular, will be discussed.     

Surgical treatment for neuroendocrine carcinoma of the uterine cervix.

OBJECTIVE: To identify the best operative approach for neuroendocrine cervical carcinoma (NECC). METHODS: The records of surgically treated patients with stages IB to IIB NECC were reviewed. RESULTS: Of 10 patients who met the study criteria for NECC and underwent radical hysterectomy, 4 had pT1bN0, 4 had pT1bN1, 1 had pT2aN0, and 1 had pT2bN1 disease. Those with pT1bN1 or pT2bN1 disease received postoperative adjuvant radiotherapy and/or chemotherapy, and recurrence occurred in 7 patients (70%). Among these 7 patients, 5 (71%) had a primary NECC tumor with deep stromal invasion and 5 (71%) had extrauterine disease (parametrium and/or lymph node). The recurrences in 6 patients (86%) were located outside the pelvis (lung, liver, or brain). Stromal invasion was 6 mm or less in the 3 patients who did not experience disease recurrence. CONCLUSIONS: Pelvic control by radical hysterectomy may not be beneficial for patients with NECC except for those with an early invasive lesion.