Premalignant and malignant lesions of the vagina

This paper will review vaginal lesions including common premalignant conditions as well as primary malignant epithelial and mesenchymal neoplasms. Discussion of the precursor vaginal squamous intraepithelial lesion (VaSIL) will precede a section focused on vaginal squamous cell carcinoma (VaSCC). The topics of adenosis and atypical endometriosis will precede discussion of vaginal clear cell carcinoma and endometrioid carcinoma. Vaginal sarcomas and adenosarcomas will be briefly addressed. Metastatic tumours which comprise the majority of vaginal malignancies will also be discussed. The review will conclude with a brief discussion of the neovagina and the rare occurrence of malignancy in this site.     

Comprehensive analysis of 130 multicentric intraepithelial female lower genital tract lesions by HPV typing and p16 expression profile

Purpose HPV associated cervical transformation is characterized by well-defined steps, including persistent HPV infection and deregulated oncogene expression. Recent studies have suggested that a number of lower genital tract lesions are clonally related to cervical lesions. In the current study, HPV infections and oncogene expression were assessed in a large series of patients with multicentric lower genital tract disease to analyze the transformation steps in extracervical disease. Methods One hundred and thirty biopsies of 52 women treated for multicentric synchronous or metachronous lower genital tract intraepithelial neoplasias were collected. Up to seven multicentric specimens taken from one patient were studied with a maximum follow up of 20 years. HPV typing and p16^ink4a immunostaining was performed. Results HPV DNA was present in 121 of 130 specimens (93%). HPV16 was frequently found in VIN, VaIN and AIN (73, 60 and 77%, respectively), whereas only 37% of CIN were HPV16 positive. Infections with identical HPV types in multicentric lesions were diagnosed in 46% of the HPV positive patients. p16INK4a expression was negative in the nine HPV negative lesions whereas about 90% of the high grade lesions showed diffuse p16 staining. Conclusion Our findings indicate that multicentric lower genital tract disease evolves through different pathways. Some cases were related to a high susceptibility towards HPV infections, while others exhibited features of clonal propagation of transformed cervical cell clones. The clinical management of the latter group is particularly challenging, because malignant cell clones can persist over a long time course. Monika Hampl and Nicolas Wentzensen contributed equally to the work.     

Nucleotide Sequence and Phylogenetic Classification of Human Papillomavirus Type 67

The complete nucleotide sequence of human papillomavirus type 67 (HPV 67) cloned from a vaginal intraepithelial neoplasia, has been determined. It consists of 7801 nucleotides with a GC content of 38.4% and exhibits similar genome organizations of genital HPVs. By phylogenetic analysis based on the full nucleotide sequences of E6 open reading frame of 28 genital HPVs, HPV 67 was clustered with HPV 16, 31, 33, 34, 35, 52, and 58. This revised version was published online in July 2006 with corrections to the Cover Date.     

Vaginal intraepithelial neoplasia (VAIN) after radiation therapy for gynecologic malignancies: a clinically recalcitrant entity

Objectives

Vaginal dysplasia is associated with prior radiation therapy (RT) for gynecologic malignancies. We reviewed our institution's experience with VAIN in patients who were treated with radiation therapy for a gynecologic malignancy.

Methods

A retrospective review of patients treated for VAIN was performed. All cases of patients followed and treated for VAIN after radiation therapy were identified (n = 10), along with a cohort of patients with VAIN who did not have radiation therapy (n = 23).

Results

Mean follow-up after initial diagnosis of VAIN was 37.6 months (range: 12 to 72). Cytologic screening events after diagnosis of VAIN (n = 105) showed that patients with prior RT were more than twice as likely to have recurrent dysplasia (OR 3.625, 95% CI = from 1.454 to 9.0376) after treatment. Of patients who recurred, the mean time to first recurrence was 12.3 months in cases and 15.3 months in controls, which was not statistically significant (p = 0.31). Screening practices at our institution ranged from 3 month to 12 month intervals. 3 patients in the RT group and 1 patient in the control group developed invasive squamous cell cancer of the vagina.

Conclusions

Vaginal dysplasia after radiation therapy is more refractory to treatment than dysplasia not associated with radiation therapy, more likely to recur after surgical and ablative therapy, and may also be more likely to progress to invasive cancer. These data support the need for further study to determine the optimal follow-up screening interval and whether aggressive surgical or ablative treatment stems disease progression in this clinical scenario.     

肝动脉、门静脉双栓化疗治疗不能切除的原发性肝癌

目的　探讨肝动脉、门静脉双栓化疗对不能切除的原发性肝癌的治疗作用。方法　对81例不能切除的原发性肝癌进行随机分组 :双栓组 41例 ,术中植入皮下埋藏式投药泵 (CDDS) ,通过药泵经肝动脉行栓塞化疗 门静脉局部灌注化疗 ;术后定期用同法栓塞化疗。肝动脉栓塞化疗(TACE )组 40例按Seldinger法进行 ,用药与术中肝动脉用药量相同。栓塞化疗 3次后 ,记录甲胎蛋白(AFP)、肿瘤大小、肝功能、体重、腹围及生存期 ,并进行比较。结果　栓塞化疗 3次后体重、AFP、肿瘤的缩小双栓组均明显优于TACE组 (P <0 .0 1) ,而肝功能、腹围无明显区别 (P >0 .0 5 )。双栓组与TACE组的中位生存期分别为 18.0个月及 11.1个月 ;6,9,12 ,2 4个月累积生存率分别为87.80 % ,78.0 % ,68.2 9%和 3 1.70 %及 70 .0 % ,5 2 .5 % ,3 0 .0 %和 5 .0 %。影响生存的因素主要是治疗方法、肝功能及肿瘤大小。结论　皮下埋藏式投药泵肝动脉、门静脉双插管栓塞化疗给药途径简单、方便、并发症少、疗效较TACE好 ,是治疗不能切除的肝癌的有效方法之一。     

Efficacy and safety of photodynamic therapy mediatied by 5-aminolevulinic acid for the treatment of vaginal high-grade intraepithelial lesions

BackgroundVaginal high-grade squamous intraepithelial lesion (HSIL) (vaginal intraepithelial neoplasia [VAIN] grade 2–3) is clinically, a precancerous lesion condition with an estimated progression rate of 10%–20%. Therefore, treatment is recommended. Because traditional treatments have limited effects, high expense and complications, here we evaluated the efficacy and safety of topical 5-aminolevulinic acid (ALA)–based photodynamic therapy (PDT).MethodsThis study consisted of 56 female patients diagnosed with vaginal HSIL. A 20% 5-ALA jelly formation was topically applied to the vaginal wall, followed by 635 nm PDT at 7–14 days intervals. Cytology, human papillomavirus (HPV) genotyping, colposcopy, and pathology were assessed after treatment.ResultsAmong the 56 patients in our study, 47 (83.9%) had VAIN 2 and 9 (16.1%) had VAIN 3. 35 patients underwent three courses of PDT treatment, 19 experienced six courses, and two experienced nine courses. The total pathological regression rate was 87.5%, and the HPV clearance rate during the 6-month follow-up was 41.9%. Lesions located in the vaginal stump after hysterectomy seem to be difficult to treat. 9%(4/44) and 23%(7/30) patients had recurrent disease during the 6-month and 1-year follow-up time point. The most common adverse event was increased vaginal discharge, other side effects include abdominal pain, vulvar pruritus, and vaginal bleeding. No severe adverse effect was observed during the treatment.ConclusionPhotodynamic therapy mediatied by 5-aminolevulinic acid is an effective and safe treatment for vaginal HSIL with minimal side effects.     

Role of vault cytology in follow‐up of hysterectomized women: Results and inferences from a low resource setting

The study was undertaken to assess the utility of cervico‐vaginal/vault cytology in the follow‐up of women treated for cervical cancer and benign gynecological conditions. Records of 3,523 cervico‐vaginal smears from 2,658 women who underwent hysterectomy and/or radiotherapy or chemotherapy, over a 10‐year period were retrieved. Data was collected on type of treatment received, indication for hysterectomy, age of patient, presenting symptoms, stage of tumor, interval since treatment, cytology and biopsy results. The results of cytology versus other parameters were analyzed separately for women treated for cervical cancer and those hysterectomized for benign indications. Malignant cells were detected in 141/1949 (7.2%) follow‐up smears from treated cervical cancer cases (140 recurrences and 1 VAIN). Around 92% of recurrences of cervical cancer were detected with in 2 years of follow‐up and 75% of these women were symptomatic. Cytology first alerted the clinicians to a recurrence in a quarter of cases. On the other hand, VAIN was detected in 5/1079 (0.46%) vault smears from 997 women hysterectomized for benign gynecologic disease. All these women were asymptomatic and majority (80%) were detected in follow‐up smears performed between 3 and 10 years. Vault cytology is an accurate tool to detect local recurrences/VAIN in women treated for cervical cancer or benign gynecological conditions. It may even first alert the clinicians to a possibility of recurrence. However, due to extremely low prevalence of VAIN/vaginal cancer, it seems unwarranted in women hysterectomized for benign indications, especially in resource constrained settings. Diagn. Cytopathol. 2013;41:762–766. © 2013 Wiley Periodicals, Inc.     

Premalignant and malignant lesions of the vagina

This paper will review vaginal lesions including the common premalignant and benign lesions as well as the rather rare primary malignant squamous and glandular neoplasms. Risk factors such as human papilloma virus, smoking and diethylstilbestrol exposure as they pertain to the development of premalignant and malignant lesions of the vagina will also be included. Metastatic tumours to the vagina, which comprise the majority of vaginal malignancies, will also be discussed.     

Management of multicentric lesions of the lower genital tract

OBJECTIVES: To report management and outcome of multicentric lesions of the lower genital tract. To define risk factors of recurrence. STUDY DESIGN: Retrospective review of multicentric dysplasias treated in our colposcopic clinic between 1996 and 2003. Multicentric dysplasias included CIN with VAIN and/or VIN. After primary treatment, follow-up was colposcopic, cytologic and virologic. RESULTS: Forty-four patients presented multicentric lesions out of 998 patients referred for CIN (4.4%). The average age was 36.8 years. Immunologic disorders were present in 20.4%. Ninety-one percent had cervicovaginal or cervicovulvar lesions, only 9% had three sites of genital dysplasia. 53.3% of lesions were concomitant. 79.5% of CIN were high grade, 62.5% of VAIN low grade and 62.5% of VIN high grade. Therapeutic modalities were as follows: conization for CIN (70.4%), CO2 laser for VAIN (33.3%) and surgery for VIN (41.7%). Forty patients were followed and had at least one post-treatment cytologic control; 55% of them had residual disease. Out of the 23 patients with at least two negative controls after treatment, 43.5% presented recurrence. Risk of recurrence was not statistically bound to such parameters as tabagism, immunologic disorder, high grade lesions, non-surgical treatment, and persistence of HPV infection after treatment. CONCLUSION: Multicentric dysplasias are associated with high rate of residual lesion and recurrence. Management of these lesions require long term follow-up.