Human papillomavirus in women with vulvar intraepithelial neoplasia III

Untreated cases of vulvar intraepithelial neoplasia (VIN) III may progress to invasive vulvar carcinoma. Tissues from 29 New Zealand women with VIN III were examined for the presence of human papillomavirus (HPV) types 6, 11, 16 and 18 by in situ hybridization and polymerase chain reaction. HPV 16, the only HPV type detected in the lesions, was identified in about half the cases. HPV-positive women were younger than HPV-negative women, and their lesions displayed koilocytosis more often. In four of five cases in which there was a progression to invasive cancer, HPV 16 was detected in both the VIN III and invasive cancer tissue.     

Human papillomavirus type 16 in vulvar carcinoma, vulvar intraepithelial neoplasia, and associated cervical neoplasia.

Vulvar intraepithelial neoplasia (VIN) is becoming more widespread and the patients are becoming still younger. Although progression to invasive vulvar carcinoma is uncommon, local recurrences are frequent and about one-quarter of the patients have multicentric genital disease. The aim of the present study was to search for a possible significant association of human papillomavirus (HPV) infection with vulvar carcinoma, recurrences, and multicentric disease. We used the polymerase chain reaction to examine vulvar and cervical biopsies from 43 patients with vulvar neoplasia for HPV type 16, which is the subtype most often detected in genital malignant or premalignant lesions. HPV 16 DNA sequences were found in 14 of 24 (58%) vulvar squamous carcinomas and in 15 of 19 (79%) VIN lesions. Nine patients (21%) had associated cervical neoplasia and six of these harbored HPV 16 in both lesions. Patients with recurrent intraepithelial neoplasia had a significantly higher incidence of HPV 16-positive lesions. No association was found with regard to the occurrence of multicentric disease or risk of malignant progression.     

Perinatal outcomes of pregnant women with cervical intraepithelial neoplasia

Objective

To investigate the perinatal outcomes of pregnant women with cervical intraepithelial neoplasia (CIN).

Method

The women in this retrospective case–control study were recruited from Beijing Obstetrics and Gynecology Hospital from August 1, 2007 to February 28, 2010. All the cases were 13–32 gestational weeks, who were diagnosed by colposcopy conducted cervical biopsy. A total of 108 cases were followed-up to the day of delivery.

Results

(1) Complications of colposcopy conducted cervical biopsy: there were two cases of pregnant women, who suffered cervical local compression after undergoing colposcopy conducted cervical biopsy, as the bleeding could not be stopped, the wound was treated by local suture. The incidence of such event was 1.8 % (2/108), without any colposcopy and biopsy-related adverse event. (2) Cesarean section rate was 63.6 % (56/88) in CIN, which was higher than 30.0 % (6/20) in cervicitis, and the cesarean section rate increased as CIN grades elevated, and gestational weeks of delivery advanced.(P < 0.05). (3) We did not detect significant difference for the incidence of polyhydramnios, premature rupture of fetal membranes, placental abruption, cervical laceration and postpartum hemorrhage, low birth weight infants, amniotic fluid II–III degree, neonatal deformity and neonatal asphyxia between pregnant women with CIN and cervicitis (P > 0.05); however, the incidence of oligohydramnios and premature infants in pregnant women with CIN group were higher than that in cervicitis group (P = 0.007; P = 0.020). (4) Vaginal delivery and HR–HPV infection did not increase the incidence of perinatal complication; the volume of postpartum hemorrhage within 2 h after birth in vaginal delivery was less than in cesearean section for pregnancies with CIN (P = 0.000).

Conclusion

Pregnant women with CIN can be diagnosed by colposcopy conducted cervical biopsy, and they should be carefully monitored oligohydramnios and preterm during pregnancy. Pregnant women with CIN during pregnancy, excluding other obstetric operation indications may choose vaginal delivery first.     

Photodynamic therapy in vulvar intraepithelial neoplasia

INTRODUCTION: Vulvar intraepithelial neoplasia may lead to vulvar cancer. Vulvar cancer is a rare (accounting for about 2,5-5% of all malignant neoplasms), female genital organs cancer. Photodynamic therapy is a new treatment for a wide variety of malignancies and premalignant dysplasias. We wanted to examine the effectiveness of photodynamic therapy (PDT) on vulvar intraepithelial neoplasia (VIN). DESIGN: The aim of the study was to analyze the effectiveness of photodynamic therapy (PDT) on vulvar intraepithelial neoplasia (VIN). MATERIAL AND METHODS: We have analyzed 20 women with VIN, who were treated in our center - Clinic of Vulvar Diseases. All these women had photodynamic diagnosis (PDD), photodynamic therapy followed (PDT), with 5% ALA applied to the entire vulva. CONCLUSIONS: We have noted the reduction of subjective complaints, but the histopathological improvement was observed in fewer degree.     

Surgical management of cervical intraepithelial neoplasia in HIV-infected women

Objective

Rates higher than 50% of positive margin after surgical treatment of cervical intraepithelial neoplasia (CIN) have been reported in HIV-infected women. We evaluated the efficacy of two excisional procedures, loop excision of the transformation zone (LLETZ) and electrosurgical conisation, in obtaining complete excision of CIN in HIV-infected patients.

Study design

Eighty HIV-infected women with CIN or suspicion of cervical cancer underwent 86 surgical excisions. The indication of surgical modalities depended on both the size and location of the lesion and on the length of the cervix. Univariate logistic regression was used to identify factors associated with positive surgical margins.

Results

Preoperative colposcopy failed to visualize the entire transformation zone in 39% of cases, and showed that 93% of the lesions had endocervical extension. LLETZ was performed in 30 cases and electrosurgical conisation in 56 cases. Resection was complete, with negative margins, in 77% of cases (95% confidence interval, CI: 62–92%) after LLETZ and in 71% of case (95% CI: 60–83%) after electrosurgical resection. Residual disease was mostly located in the endocervical portion of histological specimen. During follow-up late complications such as cervical stenosis or unsatisfactory colposcopy were not observed.

Conclusion

Endocervical extension of CIN being frequent among HIV-infected women, LLETZ should not be the preferred procedure. Appropriate surgical management leading in reducing the rate of positive margins may help decreasing the risk of persistence or recurrence of lesions.     

Adherence to follow-up in women with cervical intraepithelial neoplasia grade 1

ObjectivesAdherence to follow-up is crucial for cervical intraepithelial neoplasia grade 1 (CIN1) because these women have a chance of progression to high-grade premalignant cervical lesions and cervical cancer. This study aimed to evaluate the rate of adherence to follow-up in women who were initially diagnosed with CIN 1 over a period of 24 months and to evaluate the regression and progression rate of CIN 1.Material and methodsOf 1050 women who visited a colposcopy clinic from October 2013 through March 2017, 138 with histologically proven as CIN 1 were recruited. Adherence to follow-up, the regression and progression rate of CIN 1 were retrospectively assessed.ResultsOf the 138 women, 86 (62.3%) followed regularly until the study endpoint at 24 months. During the study period, 10 women received ablative treatment. The regression rate in women who had surveillance with cervical cytology was 69.7%, persistent disease of 18.4%, and progression to CIN 2–3 of 11.8%. In contrast, 80% of women who received ablative treatment had regression, 20% of them had persistent disease but none had progression.ConclusionsNearly 40% of women with CIN 1 were lost to follow-up at 24 months. Adherence to the follow-up should be emphasized to all women. Intensive interventions to improve adherence and clinical outcome might be an option, particularly among women with poor compliance.     

Long-term mortality in women treated for cervical intraepithelial neoplasia

Objective  The objective of this study was to study whether women surgically treated for cervical intraepithelial neoplasia (CIN) have increased mortality later in life. We also wanted to study whether pregnancy beyond 22 weeks post-treatment affects the risk.
Design  Register-based retrospective cohort study from Finland.
Setting  National data of the Hospital Discharge Register and the Cause-of-Death Register during 1986–2003.
Population  A total of 25 827 women who had surgical treatment for CIN during 1986–2003.
Methods  We calculated standardised mortality ratios (SMRs) by dividing the numbers of observed deaths (until 31 December 2006) by the numbers of expected deaths.
Main outcome measures  SMRs for different causes-of-death groups.
Results  The overall mortality increased by 17% after treatment for CIN, including increased risk of dying from all diseases and medical conditions (SMR 1.13, 95% CI 1.01–1.26), cancers (SMR 1.09, 95% CI 0.91–1.27) and injury deaths (SMR 1.31, 95% CI 1.03–1.58). As expected, the mortality from cervical cancer was high (SMR 7.69, 95% CI 4.23–11.15). Women who had delivered post-treatment tended to have decreased overall mortality (SMR 0.78, 95% CI 0.52–1.04) and decreased disease mortality (SMR 0.63, 95% CI 0.37–0.90). However, the mortality rate was significantly increased for women who had subsequent preterm delivery (SMR 2.51, 95% CI 1.24–3.78). In this subgroup, there was a tendency of increased mortality from diseases of the circulatory system, alcohol-related causes and injury deaths.
Conclusions  Mortality rate was increased after surgical treatment for CIN. However, women who had delivered post-treatment had decreased overall disease mortality rate. Subsequent preterm delivery may be a risk marker for increased long-term mortality.     

Trends in vulvar neoplasia. Increasing incidence of vulvar intraepithelial neoplasia and squamous cell carcinoma of the vulva in young women

OBJECTIVE: To determine trends in the epidemiology of vulvar intraepithelial neoplasia (VIN) and squamous cell carcinoma (SCC) of the vulva in a Central European sample during the last decade. STUDY DESIGN: A total of 366 women with VIN 2 and 3 (n = 128) or vulvar SCC (n = 238) presented within two four-year periods separated by one decade (1985-1988 and 1994-1997). We performed a retrospective analysis of the clinicopathologic records of the cohorts. RESULTS: The number of women with high grade VIN (n = 29 vs. 99) tripled during the last decade, while the incidence of vulvar SCC remained stable. In women < or = 50 years old, the incidence of high grade VIN increased by 392% (n = 12 vs. 59) and of invasive vulvar cancer by 157% (n = 7 vs. 18). In the earlier cohort there were 7/126 (5%) women with invasive vulvar SCC under the age of 50 and, in the latter cohort, 18/112 (16%, P < .01). CONCLUSION: Over the past decade a striking increase occurred in the incidence of VIN and an increase in invasive vulvar SCC in young women.     

HPV prevalence among partners of women with cervical intraepithelial neoplasia.

OBJECTIVES: The objective of this study was to find HPV DNA incidence in women with CIN and normal women and in their respective partners, as well as the relation between the virus groups found in women with CIN or normal women and in their respective partners. METHODS: Partners of 30 women with CIN at several grades and of 60 normal women were prospectively assessed. In men, HPV search was performed by collecting samples through penile scraping for Hybrid Capture, followed by peniscopic evaluation and biopsy of acetowhite lesions. RESULTS: The presence of HPV DNA in male partners does not necessarily implicate the presence of HPV or even CIN in their female partners. CONCLUSIONS: If these results are confirmed by other authors, obtaining a peniscopy, a penile biopsy, and a HPV DNA search in partners that present with no clinical lesions, but in couples with women having CIN, would not be warranted.     

New histological terminology of vulvar intraepithelial neoplasia

The International Society for the Study of Vulvar Disease (ISSVD) recommends not to use a grading any more and to include in the term vulvar intraepithelial neoplasia (VIN), usual type, the previously called VIN 2 where the nuclear atypia and mitotic figures are confined to the basal half of the epithelium and VIN 3 where nuclear abnormalities and abnormal mitotic figures are present throughout most or all of the thickness of the epithelium. VIN, usual type, is related to a human papillomavirus (HPV) high-risk type infection in most of the cases. The histologic changes previously encompassed within the term VIN 1 will be described as flat condyloma or HPV effect. The less common type of VIN lesion is termed VIN, differentiated type, previously called "high grade" differentiated type or VIN simplex type. This type of VIN is a highly differentiated lesion. The atypia is confined to the basal and parabasal layers of the epithelium, where the cells have abundant cytoplasm and form abortive pearls and the nuclei are relatively uniform in size and contain coarse chromatin and prominent nucleoli. The epithelium does not contain koilocytosis because it is not associated with HPV. It is seen primarily in older women, with a previous history of lichen sclerosus. The diagnosis is often made late in association with keratinising squamous cell carcinomas.     

Evaluation of Langerhans' cells in the cervical epithelium of women with cervical intraepithelial neoplasia.

OBJECTIVE: Cervical infection with human papillomavirus (HPV) results in a more permissive environment for malignant transformation. In squamous epithelia the Langerhans' cell (LC) is responsible for antigen presentation. Studies that use S-100 immunostaining demonstrate low LCs in cervical intraepithelial neoplasia (CIN) while those that use other methods have shown normal numbers of LCs. This observation led us to postulate that a defect in S-100 proteins, not a simple decrease in LC number, may be the cause of immune suppression. To evaluate this we identified LCs in the cervix of women with HPV/CIN in a prospective fashion using two antibodies, S-100 and CD1, each targeting a different element of the LC. METHODS: Paired biopsies of the cervix were taken, one paraffin embedded for S-100 and the other snap frozen for CD1 staining. LCs were counted and expressed as the number of cells per millimeter of epithelium. Analysis of variance was used to assess differences between counts in normal, low-grade, and high-grade lesions. HPV was tested by hybrid capture. RESULTS: S-100 LCs were significantly reduced in dysplasia, LG 8.6 and HG 6.0, compared to normal at 16.7 cells/mm (P = 0.04). S-100 LCs were reduced in HPV-infected cases at 5.9 vs 12.8 cells/mm in HPV negatives (P = 0.02). Acute inflammatory infiltrates were associated with increased S-100 LCs independent of pathology. CD1 LCs were not significantly altered by any parameters tested. CONCLUSIONS: HPV/CIN may exert an immunosuppressive effect by decreasing the S-100 LCs. The association of S-100-positive LCs coupled with cervical inflammatory changes suggests an important function of the S-100 proteins in the development of an anti-HPV response.     

CO2-laser therapy in patients with vulvar intraepithelial neoplasia

It is generally accepted to consider vulvar intraepithelial neoplasia grade III (VIN III) a premalignant condition. The lesion is more frequently diagnosed in younger patients. Conventional surgical treatment is often mutilating and recurrence rates have been reported of approximately 30%. Laser vaporization is a promising alternative therapy. Ten patients with VIN III were treated with CO2 laser. Two patients were retreated with laser for residual disease, and two patients for recurrent disease. One failure was observed, and one patient was off-study. In all patients excellent cosmetic results were obtained. Laser vaporization appears to be an effective and nonmutilating therapy, and preferable for young VIN patients.     

Cytokine profile in Indian women with cervical intraepithelial neoplasia and cancer cervix

Cervical cancer develops from the preneoplastic cervical intraepithelial neoplasia (CIN). Host factors are critical in regulating tumor growth and cytokines, which modulate immunologic control may be of particular importance. The objective of this study was to assess the production of cytokines by peripheral blood mononuclear cells (PBMCs) in Indian women with cancer cervix and CIN. Sixty patients with cancer cervix (including all FIGO stage I-IV), 35 patients with CIN, and 30 healthy controls were enrolled in this study. The human papillomavirus (HPV) 16 and 18 status was determined in all the study groups. The PBMC culture supernatant was collected for cytokine estimations by enzyme-linked immunosorbent assay (interleukin-2 [IL-2], interferon-gamma [IFN-gamma], interleukin-4 [IL-4], and interleukin-10 [IL-10]). IL-2 levels showed a significant decline in high-grade CIN and cancer patients, whereas IFN-gamma levels were decreased only in patients with advanced cancer cervix. An increase in the levels of IL-4 and IL-10 was found in all cancer cervix and CIN grade III patients, as compared to those with early CIN grades and healthy controls. The cytokine ratios decreased significantly (P < 0.001 for all the ratios), when cervical cancer patients were compared with controls and CIN cases. The type 2 and type 1 cytokine levels were significantly correlated (P < 0.000) with HPV status. We conclude that a pronounced shift from type 1 to type 2 cytokine production is associated with more severe disease. These data reinforce the need for detailed analysis of immune dysregulation in CIN and cancer cervix patients.     

2001 consensus guidelines for the management of women with cervical intraepithelial neoplasia

OBJECTIVE: The study was undertaken to provide consensus guidelines for the management of women with histologically confirmed cervical intraepithelial neoplasia (CIN) that can act as a precursor to invasive cervical cancer and represents one of the most common significant gynecologic diseases of women of reproductive age. PARTICIPANTS: An independent panel of 121 experts in various aspects of the diagnosis and management of cervical cancer precursors, including representatives from 29 participating professional organizations, federal agencies, national and international health organizations, and others were invited by the American Society for Colposcopy and Cervical Pathology (ASCCP).Consensus Process: Guidelines for the management of women with CIN were developed through a multistep process. Draft management guidelines were developed by working groups who performed formal literature reviews and obtained input from the professional community at large by way of an interactive internet-based bulletin board. At the ASCCP Consensus Conference, September 6 through 8, 2001, in Bethesda, Md, all guidelines were discussed, revised, and adopted by formal vote. CONCLUSION: Evidence-based guidelines have been developed for the management of women with biopsy-confirmed CIN.     

Treatment of vulvar intraepithelial neoplasia 2/3 with imiquimod

OBJECTIVE: To retrospectively review the charts of 13 women diagnosed with vulvar intraepithelial neoplasia (VIN) 2/3 treated with imiquimod and to evaluate the efficacy of this treatment. STUDY DESIGN: Retrospective review. All 13 women were treated and evaluated by a single gynecologist. The extent of the lesions prior to treatment and the extent and degree of improvement were documented. Biopsy confirmation of disease was obtained for each individual. Response to treatment was categorized as complete regression, at least 75% regression or not improved. RESULTS: The mean duration of treatment was 3.3 months, and follow-up after completion of therapy was 5.5 months. Eight of the 13 women had complete regression of the VIN. Four patients demonstrated 75% regression of disease, and in one diabetic woman no improvement was seen. In two women demonstrating 75% lesion regression, invasive carcinoma of the vulva was found in the area of residual disease. In one instance this was determined to be superficially invasive squamous cell carcinoma (1 mm of invasion), and in the second an anal tag was found to have invasive squamous cell carcinoma. CONCLUSION: Medical management of VIN 2/3 with imiquimod is worth considering. However, careful evaluation of the patient must be carried out prior to the institution of therapy to exclude the presence of invasive squamous cell carcinoma.