HPV genotyping in adenocarcinoma of the uterine cervix in Thailand

Objective

To determine the distribution of human papillomavirus (HPV) genotypes in cervical adenocarcinoma in Thailand and to evaluate the clinicopathologic characteristics associated with common HPV genotypes.

Methods

Formalin-fixed, paraffin-embedded tissues from 150 patients with adenocarcinoma were collected from 4 areas of Thailand. Infection with HPV was detected by nested polymerase chain reaction (PCR) with primers MY09/11 and GP5 +/6 +. Genotyping was performed using a linear array assay, followed by type-specific PCR targeting the E6/E7 regions of HPV-16, HPV-18, and HPV-52 if the linear array test was negative.

Results

Human papillomavirus DNA was detected in 145 (97%) adenocarcinomas (132 single infections; 11 multiple infections; 2 tumors with undetermined HPV type). Genotype 18 was most common (66%), followed by HPV-16 (30%) and HPV-45 (3%). Infection with only HPV-16 and/or HPV-18 accounted for 88% of the HPV-positive tumors. Patients with HPV-18 infection had a younger age (P = 0.009) and higher tumor grade (P < 0.001) than patients with HPV-16 infection.

Conclusion

The HPV detection rate in cervical adenocarcinomas in Thailand is high. The predominant genotype is HPV-18, being twice as common as HPV-16. Genotype variations are associated with patient age and tumor grade. Vaccination against HPV-16/HPV-18 might prevent almost 90% of adenocarcinomas.     

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.     

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.     

Fertility-sparing treatment in younger women with adenocarcinoma in situ of the cervix

Objective

For women who have completed childbearing, the treatment of choice for adenocarcinoma in situ (ACIS) of the cervix is hysterectomy. In women who desire future fertility, however, conservative therapy is an acceptable alternative. In this study we compare the outcomes for young women who underwent loop conization or were treated with cold knife conization.

Methods

We performed a retrospective analysis in 112 patients with ACIS, age 30 or younger, treated with cold knife conization or loop conization between 1998 and 2010. Decision to perform office loop conization was based on the size of the cervix and the colposcopic lesion. Main outcomes were negative margins after the procedure and recurrence of ACIS.

Results

Fifty-eight patients (52%) were treated with cold knife conization and 54 (48%) underwent loop conization. The odds ratio for cold knife conization to achieve negative cone margins compared with loop conization was 1.4 (95% CI 0.6-3.5). We observed no difference in residual or recurrent ACIS between patients treated with loop conization versus cold knife conization.

Conclusions

In select young patients who desire future fertility, loop conization and cold knife conization have equivalent rates of negative margins and negative follow-up. For optimal results, patients must have a lesion which can be removed in one pass of a loop, confirmed by expert colposcopy. Loop excision should be considered the treatment of choice in this specific group of patients.     

The role of the loop electrosurgical excision procedure in the diagnosis and management of early invasive cervical cancer

The management of cervical intra-epithelial neoplasia (CIN) has evolved so that excisional techniques are now preferred over ablative procedures. This is in part due to a 1–3% rate of discovering unsuspected early invasive carcinomas that would not have been detected by ablative management of CIN. A review of our initial experience over 20 months with the loop electrosurgical excision procedure (LEEP) in treating CIN found seven out of 237 patients (3%) to have otherwise unsuspected invasive lesions. The management of three additional patients with suspected early invasive lesions has been facilitated by LEEP. The procedure has been found to produce excellent pathologic specimens and has virtually replaced traditional operative cervical conization in the management of both CIN and early invasive cervical cancer.     

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.     

Adenocarcinoma in situ coexisting with carcinoma in situ of the cervix during pregnancy

Case report We report a pregnant patient with adenocarcinoma in situ (AIS) coexisting with carcinoma in situ (CIS) of the cervix diagnosed by conization at 16 weeks' gestation. Apoptotic activity was higher in the CIS lesion than in the AIS lesion in the cone biopsy specimen. Postpartum evaluation confirmed the disappearance of CIS lesion with positive cone margins, however, multifocal AIS with negative cone margins was found. Conclusion Clinical course and biological features of AIS associated with pregnancy may be different from those of CIS.     

Factors predicting the outcome of conservatively treated adenocarcinoma in situ of the uterine cervix: an analysis of 166 cases

Objective

The present study assessed the clinical outcome of patients conservatively treated for cervical adenocarcinoma in situ (AIS) and their predictive factors using univariate and multivariate population averaged (PA) generalized estimating equation (GEE) model in a longitudinal setting.

Methods

A series of 166 consecutive women (mean age 39.8 yrs; range 23-63 yrs) underwent conservative treatment of AIS as the primary treatment and were followed-up (mean 40.9 mo) using colposcopy, PAP-smear, biopsy and HPV-testing with Hybrid Capture 2.

Results

Hysterectomy was performed as part of the primary management in 47 patients, who were excluded from the follow-up (FU) analysis. Out of 119 women closely followed-up, additional therapeutic procedures were performed in 69. At study conclusion, 7 patients (5.9%) showed persistent disease, while 8 (6.7%) had progressed to invasive adenocarcinoma (AC). Positive HR-HPV test was the only independent predictor of disease recurrence (adjusted OR = 2.72; 95%CI 1.08-6.87), and together with free cone margins (OR = 0.20; 95%CI 0.04-0.92), HR-HPV positivity was also the single most powerful predictor of disease progression to AC, with OR = 3.74; 95%CI 1.84-7.61 (p = 0.0001) in multivariate PA-GEE.

Conclusions

These results suggest that testing HR-HPV positive at any time point during FU is the most significant independent predictor of progressive disease, while showing free margins in cone has a significant protective effect against progression to AC. Furthermore, because 4.3% women with persistent, recurrent or progressive disease experienced a late (5th and 6th FU) diagnosis of HG-CGIN or microinvasive AC, a close surveillance should be scheduled for at least three years in conservatively treated AIS patients.     

宫颈电环切除术后至妊娠的时间间隔对妊娠结局的影响

目的：探讨宫颈电环切除术（LEEP）术后至妊娠的时间间隔对妊娠结局的影响。方法：收集2000年-2010年LEEP术后准备生育的106例妇女为病例组,随机抽取同期门诊准备生育、无宫颈治疗史的106例健康妇女为对照组。比较两组的妊娠率及妊娠方式。按LEEP术后至受孕的时间间隔,将病例组中妊娠者分为3组：术后12月内、术后13-24月和25月后组,比较3组孕妇的妊娠结局。结果：病例组中1例失访。病例组与对照组的妊娠率分别为98.10%（103/105）和99.06%（105/106）;自然妊娠率分别为99.03%（102/105）和99.05%（104/106）;剖宫产率分别为37.14（39/105）和35.85%（38/106）,两组比较均无显著差异（P〉0.05）。两组的剖宫产原因不同,病例组中因高龄因素行剖宫产者显著高于对照组（P=0.001）。病例组中术后12个月内、13-24个月和25个月后妊娠者分别有27例、43例和32例,3组的流产、早产、胎膜早破和剖宫产率均无显著差异（P〉0.05）。结论：LEEP术后至妊娠的时间间隔不影响患者的受孕及妊娠结局。     

高频电波刀行电圈切除治疗宫颈病变的临床应用探讨

目的　评价高频电波刀行电圈切除 (LEEP)治疗宫颈病变中的临床应用价值。方法　回顾性分析我院 2 71例LEEP治疗宫颈病变的临床资料 ,所有病例均行阴道镜下多点活检和LEEP术后病理诊断 ,在炎症和赘生物病变外缘 3mm进出电极 ,对于CINI与HPV感染患者 ,电极在病变边缘外 5mm进出。结果　阴道镜下多点活检与LEEP术标本的病理诊断差别有显著性 (P <0 0 5 )。 2 71例患者术后随访 2 4 3例 ,术后复查宫颈细胞学 ,仅 9 0 5 %出现细胞核肥大和核异质。结论　LEEP对包括炎症、损伤、癌前病变、HPV感染等宫颈病变是一种非常理想的诊断、治疗手段。宫颈细胞学检查、阴道镜下多点活检、LEEP术后病理诊断构成了宫颈病变系统的诊断模式。LEEP可以广泛地应用于治疗CIN各级病变 (原位癌除外 ) ,LEEP也适用于CINI的治疗 ,LEEP治疗的范围可以在病变边缘外 5mm处进出电极     

Conization using the Shimodaira-Taniguchi procedure for adenocarcinoma in situ of the uterine cervix

Objective

The Shimodaira-Taniguchi conization procedure addresses the disadvantages of the loop electrosurgical excision procedure (LEEP) by using a high frequency current and a triangular probe with a linear excision electrode to extract the tissue as a single informative specimen, without incurring accompanying thermal trauma. The aim of the present study was to analyze the surgical efficacy of the Shimodaira-Taniguchi conization procedure for adenocarcinoma in situ (AIS) of the uterine cervix.

Study design

At the Osaka University Hospital, conization using the Shimodaira-Taniguchi procedure has long been routinely performed for AIS. Medical records of patients during the period from 2005 to 2011, whose post-conization diagnosis was AIS, were retrospectively analyzed. A literature review was conducted of the PubMed database to clarify the surgical outcome efficacy of the Shimodaira-Taniguchi procedure compared to other procedures.

Results

During the study period, a post-conization diagnosis of AIS was made in 10 patients. A positive resection margin was detected in 4 of the 10 cases (40%), and residual disease was observed in 3 cases (30%). A review of the relevant literature indicates that the rate of positive margin and residual disease by the Shimodaira-Taniguchi procedure, including our cases, was not significantly different from the cold knife, LEEP or laser procedures (p = 0.32, 0.99, and 0.40, respectively, for positive margin, and p = 0.76, 0.94, and 0.063, respectively, for residual disease).

Conclusion

AIS was demonstrated to be efficaciously treated, with a low risk of residual disease, by the Shimodaira-Taniguchi conization procedure. Further study is still needed to establish a standard of conservative treatment for AIS.     

The basement membrane in the carcinoma in situ of the cervix: A morphological study

A morphological study of the basement membrane in the carcinoma in situ of the cervix has been carried out.Undifferentiated carcinoma in situ that arises usually from the squamocolumnar junction and which extends into the endocervical canal, always shows a continuous and clearly delineated basement membrane, which runs parallel to the basal layer. It has a homogeneous appearance. The hemidesmosomes attached to the lamina propria are quite normal and there are no slender protrusions from basal cells into the lamina propria.Differentiated carcinoma in situ, that originates in the squamous epithelium of the portio, may extend either in the direction of vagina, or towards the endocervical canal. It is always underlined by a basement membrane loosely constituted of irregular or fragmented reticular fibers; it frequently looses its homogeneous appearance and may be dehiscent or duplicated. Basal cells send down small pseudopods or threadlike extensions into the lamina propria.The authors suggest that in the management of carcinoma in situ of the cervix, one should take into consideration the direction of spread and the stroma-invasion potential of the carcinoma. These histologic patterns carry with them a very important morphologic implication, namely ‘cells differentiation’ of the carcinoma.     

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.)     

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.     

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.     

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.     

Psychologic morbidities prior to loop electrosurgical excision procedure in the treatment of cervical intraepithelial neoplasia

The objective of this study was to assess and compare anxiety and distress in patients undergoing colposcopic examinations and loop electrosurgical excision procedure (LEEP). Patients seen for evaluation of cervical intraepithelial neoplasia (CIN) and LEEP were recruited. All patients received further teaching with respect to their abnormality right after the colposcopic evaluation by nursing staff. The Hospital anxiety and Depression Scale (HADS) and the Psychosocial Effects of Abnormal Pap Smears (PEAPS) questionnaires were used to measure and compare distress between the two groups. Linear regression models were built to identify significant predictive variables for psychologic morbidities. Twenty-one colposcopy and 20 LEEP patients participated in this study. No significant demographic differences were noted. Eighty-one percent of patients having colposcopy and 65% of those undergoing LEEP can be classified as having significant anxiety and depression based on the HADS questionnaire. Patients undergoing LEEP scored significantly better than colposcopy patients on the mean total PEAPS score and on the self-belief/cancer concern and effects on sexual relationship dimension scores. Significant psychologic morbidities exist in patients diagnosed with CIN. Face-to-face individualized education and support after colposcopy can decrease patients' distress at subsequent treatment visits.