Human papillomavirus genotype as a prognostic indicator in carcinoma of the uterine cervix

The clinical implications of specific human papillomavirus (HPV) types in invasive cervical carcinomas are only beginning to be appreciated. In this series of 100 women with cervical cancers analyzed for the presence of HPVs 6, 11, 16, 18, and 31 by Southern blot hybridization, a more aggressive clinical behavior was demonstrated for tumors containing HPV 18 than for those with HPV 16 or those in which no HPV was identified. Among 69 stage Ib tumors, no significant differences were found in the size of tumor, presence of parametrial involvement, or lymph node metastasis among patients whose tumor contained HPV 16, HPV 18, or no HPV DNA; however, 45% of the women with HPV 18-containing tumors (five of 11) had recurrence, as compared with only 16% of those with HPV 16 (five of 31) during the 20-month mean follow-up period. This tendency for HPV 18-containing tumors to recur was seen with all histologic subtypes of cervical cancers and with all grades of tumor. In addition, patients with HPV 18-containing tumors were more likely to give a history of recent normal Papanicolaou smears than were those whose tumors contained HPV 16. Forty-four percent of women with HPV 18 in their tumors had a history of three class I Papanicolaou smears in the 3 years before the diagnosis of cancer, whereas a similar history was elicited in only 16% of those with HPV 16 in their tumors, suggesting that HPV 18-containing tumors might progress to invasion without a prolonged preinvasive period.     

Radiotherapeutic management in carcinoma of the uterine cervix: current status

Despite refinement in the delivery of external radiation and brachytherapy, there has been little improvement in the survival rate of patients with invasive cancer of the uterine cervix in recent years. With advancing stage disease, there is an increase in both local failure and distant metastases. Although recent efforts to improve local control for late stage disease have been encouraging, research efforts should be directed to the identification of new active drugs for radiation sensitization and systemic therapy. Also, due to early detection, therapeutic investigations should focus on the high-risk subsets of patients with early stage disease.     

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.     

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.     

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.     

Assessment of pelvic lymph node micrometastatic disease in stages IB and IIA of carcinoma of the uterine cervix

The objective of this study was to assess the frequency of micrometastatic disease (MID) in pelvic lymph nodes (PLNs) in carcinoma of the uterine cervix (CUC) and to determine the risk of recurrence. The PLNs from 289 patients with CUC (IB and IIA) were studied. Each PLN was assessed via immunohistochemistry using a single histologic section (AE1/AE3). Metastatic deposits were measured and the disease status was classified into three groups: 1) absence of metastatic disease (MOD); 2) MID, one or more metastatic PLN with only isolated tumor cells and/or micrometastases (up to 2 mm); and 3) macrometastatic disease (MAD), presence of one or more metastatic PLN with macrometastases (more than 2 mm). Eleven patients (3.8%) were classified as having MID and 37 (12.8%) as having MAD. The 5-year disease-free survival (DFS) rates for MOD, MAD, and MID were 88.7%, 80.4%, and 50.0%, respectively (P < 0.001). The Cox proportional hazards model showed that MID was an independent variable for recurrence when adjusted for MAD, depth of tumor invasion, severity of inflammatory reaction, and use of adjuvant radiotherapy. We conclude that the frequency of MID in PLN was low. However, patients with MID presented a high risk of recurrence and reduced DFS.     

Telomerase activity in the vaginal margins of radical hysterectomy in patients with carcinoma of the cervix: correlation with histology and human papillomavirus

This study was undertaken to evaluate the telomerase activity both in the tumor and in the vaginal margins of radical hysterectomy in patients with squamous cell carcinoma (SCC) of the cervix. Thirty-three patients with SCC of the cervix (study group) and 13 patients with uterine myoma (control group) were prospectively studied. Tissue samples were taken from the tumor or cervix, anterior vaginal margin (AVM), and posterior vaginal margin (PVM). The specimens were analyzed by histopathology, by a telomerase PCR-TRAP-ELISA kit, and by polymerase chain reaction using human papillomavirus (HPV) DNA. The telomerase activity was significantly higher in the tumor than in the benign cervix (P < 0.001). There was no difference in telomerase activity in the AVM and PVM in patients with cervical carcinoma compared to the control group. Telomerase activity was associated with the presence of histologic malignancy in the PVM of patients submitted to radical hysterectomy (P= 0.03). This association was not observed with the presence of HPV in AVM or PVM in the study group. Telomerase activity is a marker of histologic malignancy in patients with SCC of the cervix. There was no association between the telomerase activity and the presence of HPV in vaginal margins of patients submitted to radical hysterectomy.     

宫颈鳞癌和上皮内瘤变组织中TRF1、TRF2及HPV16、HPV18的检测及其意义

目的研究端粒结合蛋白TRF1、TRF2在宫颈鳞癌发生发展中的作用并分析HPV16、HPV18感染与TRF1、TRF2蛋白表达的关系。方法随机选择南华大学附属第一医院病理科2005年9月至2006年10月期间的组织石蜡块标本共86例,采用原位杂交方法检测HPV16、HPV18在15例正常宫颈上皮、36例宫颈上皮内瘤变(CIN)和35例宫颈鳞癌组织中的感染情况;采用免疫组化方法检测所有组织标本中TRF1、TRF2蛋白的表达。结果(1)HPV16、HPV18阳性感染率CIN组[63.9%(23/36)]和宫颈鳞癌组[97.1%(34/35)]显著高于正常组[20.0%(3/15)](χ2=30.639,P<0.01)。(2)TRF1阳性表达率宫颈鳞癌组[40.0%(14/35)]显著低于CIN组[63.9%(23/36)]和正常组[86.7%(13/15)](χ2=10.237,P<0.01);CINⅢ组[42.9%(6/14)]显著低于CINⅠ组[90.0(9/10)](χ2=5.531,P<0.01)。TRF2阳性表达率宫颈鳞癌组[80.0%(28/35)]显著高于CIN组[52.8%(19/36)]和正常组[...     

A matched study of surgically treated stage IB adenosquamous carcinoma and adenocarcinoma of the uterine cervix

Thirty-eight patients with surgically treated stage IB adenosquamous carcinoma of the uterine cervix (AS) have been matched with patients with other histologic subtypes of adenocarcinoma (A) for stage, lesion size, node status, grade of adenocarcinoma and age at diagnosis. An additional six patients with AS were unable to be matched. Overall 5-year survival and disease-free survival for the matched AS and A were not significantly different, 83 vs. 90%, and 78 vs. 81% nor were the number of recurrences, 8/38 AS vs. 6/38 A, but the mean time to recurrence was significantly shorter in the AS group: 11 vs. 32 months ( P = 0.003). A subgroup of AS with a high risk of a poor outcome can be identified based on either lesion size ≥ 4 cm, depth of invasion ≥ 10 mm or plevic lymph node metastasis. These patients may be suitable candidates for adjuvant therapy before or after surgical treatment.     

Small cell carcinoma of the cervix

Small cell carcinoma of the cervix is an uncommon aggressive variety of cervical cancer. Between 1982 and 1993, eight cases of this disease were diagnosed at the Queensland Centre for Gynaecological Cancer among 1586 cervical cancers. Treatment results have been poor with one long-term survivor. Literature review suggests that aggressive chemotherapy combined with surgery and/or radiotherapy may improve survival.     

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.     

Human papillomavirus (HPV) genotyping by HPV DNA chip in cervical cancer and precancerous lesions

OBJECTIVES: The human papillomavirus (HPV) is a well-known cause of cervical cancer. HPV tests are used as an adjunct test to decrease the false-negative rate of cytological screening. However, attempts are being made to replace the cytological screening with HPV tests. Therefore, this study was performed to examine the possibility of using HPV tests as screening test. MATERIALS AND METHODS: The results of the tests that were performed at the same time including the ThinPrep cytology, the high-risk group hybrid capture II (HC-II) test, the HPV DNA chip (HD-C) test, and a punch biopsy were compared in 400 women who were referred to us due to abnormal cytology or cervicogram. The accuracy of each test was then evaluated, and the type of virus was investigated using a HD-C test. RESULTS: The positive predictive values detected by the high-risk group HC-II test and HD-C test according to the histological diagnosis outcomes were 56.8 and 53.8%, respectively, for cervicitis; 91.5 and 91.5%, respectively, for cervical intraepithelial neoplasia I (CIN I); 88.1% and 81.0%, respectively, for CIN II; 88.6 and 84.2%, respectively, for CIN III, and 92.5 and 88.7%, respectively, for cancer (in 53 patients). The most prevalent types of HPV according to the HPV tests were types 16, 58, 18, and 52 in which type 16 was detected in the more advanced lesions. The sensitivity was 88.4% for the ThinPrep cytology, 89.9% for the HC-II for the high-risk group, and 86.2% for the HD-C test. CONCLUSION: These results suggest the possibility of using the HC-II and HD-C tests as screening tests, which have a similar sensitivity as the ThinPrep cytology. Nonetheless, randomized controlled trials will be needed before the actual application of the HPV tests as screening tests. Despite the fact that the importance of HPV type 16 in cancer development was confirmed, the prevalence of types 58 and 52 were relatively high compared with those found in other studies, showing a need for further studies on this subject. These HPV types need to be considered in vaccine development.     

An asymmetric, posterior spacing system for use withmini-ovoids in the treatment of carcinoma of the cervix

Stevens CW, Benjamin I, Epperson RD, Rubin SC, Solin LJ. An asymmetric,posterior spacing system for use with mini-ovoids in the treatment of carcinomaof the cervix. Int J Gynecol Cancer 1997; 7 : 350–354.
Customized brachytherapy implants are an important component of themanagement of patients with carcinoma of the cervix. An asymmetric,posterior-spacing system was designed toimprove the ability to deliver customized brachytherapy implants. This systemattaches to standard mini-ovoids to selectively increase the distance betweenthe ovoids and rectum,thereby reducing the radiation dose to the rectum. The posterior spacing systemis used at the time of tandem and ovoid placements that require mini-ovoids.Minimal operative timeis required, and no loading adjustments are needed. The system can besterilized and re-used. Significant rectal dose reduction in the range of10% to 25% can be achieved.This posterior spacing system has several advantages over typical packing inmini-ovoid applications: (1) Since mini-ovoids are only used in patients withnarrow vaginal vaults,the posterior spacing system provides guaranteed spacing in tight surroundings;(2) The spacing system is rapid to employ, thereby minimizing anesthesia time;(3) The spacingsystem will not slip out of position. The asymmetric posterior spacing systemis useful for patients in whom selective posterior spacing is required toreduce the radiation dose tothe rectum from brachytherapy using tandem and ovoids for the treatment ofcarcinoma of the cervix.     

Vimentin intermediate filament expression in uterine cervical carcinoma

The expression of vimentin intermediate filament has been examined in 62 cases of stage IB/IIA uterine cervical carcinoma as it has been demonstrated that some vimentin-positive epithelial neoplasms arising in the breast, stomach and kidney have an aggressive clinical behavior. No correlation was found between vimentin staining in cervical carcinomas and tumor differentiation, lymph node status or clinical outcome although vimentin-positive adenocarcinomas had a non-statistically significant tendency to lack metastases.
Despite being over-expressed in each of the three main tumor subtypes, it appears unlikely that vimentin analysis will prove to be useful as a prognostic indicator in uterine cervical carcinoma.     

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.     

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.     

Small-cell carcinoma of the uterine cervix: a clinicopathologic study of 11 cases

We report the clinical profiles and immunohistochemical features of small-cell carcinoma of the uterine cervix. Eleven cases that we have encountered at the Department of Gynecology, Kitasato University Hospital, between 1971 and 2003 are presented. Of 1370 invasive carcinomas of the uterine cervix, the incidence of small-cell carcinoma was 0.8%. Patient ages ranged between 32 and 65 years, with a mean age of 46.3 years. The clinical stages at diagnosis were Ib in four patients, IIb in three, IIIb in three, and IVb in one. All patients presented with abnormal vaginal bleeding. Two patients who are alive with no evidence of disease for 12 years and 3 years 6 months, while eight patients died of primary carcinoma between 4 and 25 months after treatment. Histopathologic findings showed solid nests with marked peripheral palisading pattern and rosette formation. Small tumor cells with scant cytoplasm demonstrated a very high nuclear/cytoplasm ratio and indistinct cell borders. The nuclei were round to oval and demonstrated increased but fine granular chromatin. Nucleoli were indistinct in all cases. Immunohistochemical findings were positive in 81.8% each for neuron-specific enolase and protein gene product 9.5, 72.7% for synaptophysin, 63.6% for chromogranin A, and 54.5% for neural cell adhesion molecule. All specimens were positive for at least one of the above. In conclusion, small-cell carcinoma of the uterine cervix revealed poor prognosis. Making an accurate diagnosis of small-cell carcinoma before performing treatment is of great significance but often difficult. Immunohistochemical analysis using several kinds of neuroendocrine markers is helpful in establishing the correct diagnosis in addition to focusing on characteristic histo- and cytopathologic features.     

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.     

Multisystem sarcoidosis and carcinoma of the uterine cervix: An unusual association

Abstract. Alliot C, Barrios M, Desplechain C. Multisystem sarcoidosis and carcinoma of the uterine cervix: An unusual association.
Sarcoidosis malignancy syndrome is a rare phenomenon which remains controversial. We report here the case of a 46-year-old woman presenting with multisystem sarcoidosis 12 months after the completion of combined treatment for stage III squamous cell carcinoma of the uterine cervix; at the time she was still in complete remission of the tumor. The outcome was rapidly favorable under oral corticosteroid therapy. The time interval between the two illnesses as well as patient's age strongly suggest a relationship. Possible pathophysiologic mechanisms and the literature regarding uterine tumors are briefly reviewed.     

Large cell neuroendocrine carcinoma of the uterine cervix: a report of a case and review of the literature

Introduction Large cell neuroendocrine carcinoma is a rare aggressive cervical neoplasm, considerably rarer than the well-recognized small cell neuroendocrine carcinoma of the cervix. Cervical large cell neuroendocrine carcinomas are distinctive cervical carcinomas that are frequently misdiagnosed and have an unfavorable outcome, similar to that of small cell carcinoma. Case report We report a 45-year-old woman with large cell neuroendocrine uterine cervical carcinoma.