Persistent Cervical Intraepithelial Neoplasia Research Articles

Human papillomavirus self-sampling and urine-sampling tests and the management and short-term outcomes of cervical intraepithelial neoplasia: A prospective observational study.

The importance of human papillomavirus (HPV) co-testing using physician-, self-, and urine-collected samples to predict cervical intraepithelial neoplasia (CIN) grade 1-2 prognoses has not been previously reported. Therefore, this study aimed to investigate outcomes of patients with CIN 1-2 who simultaneously underwent physician-, self-, and urine-collection sampling tests. This study was conducted in Japan between October 2019 and November 2022 and examined the proportion of cases with CIN 1-2 progressions, the percentage of cases with persistent CIN 1-2, and the outcome differences according to the results of physician-, self-, and urine-sampling tests. There were 105 and 59 CIN 1 and 2 cases, respectively, with progression or persistence in 27 (29.3%) and 21 (50.0%) cases, respectively. The median follow-up was 20 and 12 months, respectively. Progression and persistence of CIN 1 were significantly associated with HPV-positive physician- and self-collected samples. No significant difference was observed between cases with CIN 2 who had HPV-positive and HPV-negative results using any sampling method. Physician- and self-testing for HPV are crucial for predicting disease progression risk in CIN 1 cases. Future research with an extended observation period and consideration of the progression risks is warranted.

Clinical efficacy of recombinant human interferon α-2b gel combined with LEEP conization in treating cervical intraepithelial neoplasia with comorbid high-risk HPV infection.

To evaluate the clinical efficacy of recombinant human interferon α-2b (rHuINF α-2b) gel combined with loop electrosurgical excision procedure (LEEP) conization in treating cervical intraepithelial neoplasia (CIN) with comorbid high-risk human papillomavirus (HR-HPV) infection. A retrospective analysis was conducted on the clinical data of 202 CIN patients with HR-HPV infection who were treated at Wuhan Yaxin General Hospital between July 2021 and February 2024. Among these patients, 106 received treatment with rHuINF α-2b gel combined with LEEP conization (study group), and the other 96 were treated with LEEP conization alone (control group). The two groups were compared in terms of efficacy on CIN, HPV clearance, vaginal bleeding duration, hospital stay and occurrence of adverse reactions. Patient prognosis within six months post-treatment was analyzed, and the risk factors affecting prognosis were analyzed through logistic regression. The control group experienced notably longer vaginal bleeding duration and hospital stay than the study group (all P<0.0001). The study group showed a notably higher cure rate of CIN than the control group and presented a notably lower rate of persistent or residual CIN than the control group (P=0.0026). Six months after treatment, the total effective HPV clearance rate in the study group was greatly higher than that in the control group (P=0.0010). However, there was no insignificant difference between the two groups in the incidence of adverse reactions (P=0.4807). According to logistic regression analysis, age, grade of CIN, course of disease and treatment regimen were independent risk factors for patient prognosis. For CIN patients with comorbid high HPV risk infection, rHuINF α-2b gel combined with LEEP conization can effectively treat CIN, clear HPV, and shorten the duration of vaginal bleeding and hospitalization, without increasing adverse reactions. In addition, age, grade of CIN, course of disease and treatment regimen were independent risk factors for the prognosis of patients.

TRICIN: A Phase II Trial on the Efficacy of Topical TRIchloroacetic Acid in Patients with Cervical Intraepithelial Neoplasia.

Data on non-surgical treatment approaching persistent cervical intraepithelial neoplasia (CIN) are scarce. Retrospective analysis suggest high efficacy of topical treatment with trichloroacetic acid (TCA). This prospective phase II study set out to investigate the efficacy of a single application of 85% TCA in the treatment of CIN I/II. Patients with CIN I/II were treated a single time with 85% TCA. After three and six months colposcopic, histologic, and HPV evaluation was performed. The primary endpoint was treatment efficacy defined as complete histologic remission six months after treatment. The secondary endpoint was HPV clearance six months after treatment. A total of 102 patients with CIN I/II were included into this trial. Complete histologic remission rates were 75.5% and 78.4% three and six months after TCA treatment, respectively. Clearance rates of HPV 16, 18 and other high risk types were 76.5%, 91.7%, 68.7% after six months, respectively. Side effects of TCA were mild and lasted usually less than 30 min. This is the first prospective trial reporting high histologic complete remission rates in patients with CIN I/II after a single 85% TCA treatment. In the future, TCA may represent an effective and feasible non-surgical treatment approach for CIN.

Cervical intraepithelial neoplasia grade 3: development during pregnancy and postpartum

PurposeThe aims of the present study were to evaluate the development of untreated cervical intraepithelial neoplasia (CIN) 3 during pregnancy and to assess persistence, progression, and regression rates postpartum to identify factors associated with regression.MethodsIn a tertiary gynecology and obstetrics department, a total of 154 pregnant women with CIN 3 were treated in the dysplasia unit. The follow-up findings were analyzed retrospectively on the basis of histological, cytological, and human papillomavirus (HPV) testing of 154 pregnant women confirmed as having CIN 3 in colposcopically guided biopsies.ResultsThe rates of persistence, regression, and progression of CIN 3 in these women were 76.1%, 20% and 3.2%, respectively. Data for the delivery mode was available for 126 women. The rate of regression was almost twice as high with vaginal delivery as with cesarean section, at 27.4 vs. 15.2%, whereas the rate of progression was lower with vaginal delivery, at 2.7 vs. 6.5%.ConclusionThe rate of persistence of CIN observed in this study is comparable to that reported in other studies. The study provides strong evidence for greater regression among women who have vaginal deliveries. Careful work-up is recommended postpartum for this group of women in order to rule out persistent CIN 3 or invasive disease.

Aerobic Vaginitis: is Enterococcus faecalis Another Risk Factor in the Progression of Cervical Intraepithelial Neoplasia to Cervical Cancer—Literature Review

Objective: The aim of our review article is to show Enterococcus faecalis (E. faecalis) as a risk factor of cervical cancer. Mechanism: Aerobic vaginitis (AV) is the absence of a balance of vaginal flora containing aerobic and intestinal pathogens, varying degrees of vaginal inflammation and immature epithelial cells. The causes of AV responsible for inflammatory changes are: E. faecalis, Esherichia coli, group B streptococcus and Staphylococcus aureus. The pathogenic effect of aerobic microorganisms such as E. faecalis shows that it causes spontaneous abortion, premature birth, puerperal sepsis, abscesses, and urinary tract infections. Findings in Brief: AV caused by E. faecalis is more common in low-grade and high-grade cervical intraepithelial neoplasia (CIN) than in women with a normal Pap test and is thought to contribute to the progression of cervical cancer. E. faecalis produces hydrogen superoxide which causes chromosomal instability in intestinal epithelial cell infection, which is considered a key factor in the carcinogenic process. The presence of the Human papilloma virus (HPV) 16 gene and genome in E. faecalis in cervical cancer biopsy material leads to a specific link that may be a risk factor in the progression of CIN toward cancer. The presence of HPV in this bacteria can lead to persistent HPV infection, CIN development and progression to cervical cancer. Conclusions: Increased vaginal pH, lactobacilli deficiency, and the ability of E. faecalis to contain HPV-16 in episomal form in E. faecalis-induced AV could be key promoters of persistence and proliferation of cervical HPV as a risk factor in development of CIN and cervical cancer.

Effects of the menstrual cycle on cytological false-negatives in women with persistent cervical intraepithelial neoplasia.

False-negatives on cytology may be observed during follow-ups for patients with persistent cervical intraepithelial neoplasia (CIN); however, the underlying reasons are unknown, and the relationship between the intra-individual variability of false-negatives and the menstrual cycle phase has not been elucidated. Therefore, this study aimed to determine whether the menstrual cycle influences cytological results to maximise the accuracy of such tests. A total of 154 liquid-based cytological (LBC) samples were obtained during follow-ups for 26 patients with CIN, and the relationship between cytological results and the menstrual cycle, which was classified into six phases, was analysed. All LBC smears were satisfactory, and 20 of 154 (13.0%) specimens were negative for intraepithelial lesions or malignancy (NILM). A statistically significant association was observed between the cytological results and the phase of the menstrual cycle, χ2 (2)=19.322, P < 0.01. The association was moderately strong (Cramer's V=0.354). The value of adjusted residuals showed a statistically significant increase in the NILM percentage as a cytological result during the early secretory phase (P < 0.01) and a statistically significant decrease in NILM during the menstrual and proliferative phases (P < 0.01). The present study revealed that false-negative cytological results were found to more likely to occur during the early secretory phase. More careful and precise microscopic observation of Pap smears collected at the early secretory phase may contribute to a reduction in the occurrence of false-negatives and improve cytological sensitivity.

Predictors of Absent High-grade Cervical Intraepithelial Neoplasia (CIN) in Loop Electrosurgical Excision Procedure Specimens of Patients with Colposcopic Directed Biopsy-Confirmed High-Grade CIN

Objective:To determine predictors of having cervical intraepithelial neoplasia (CIN) 1 or less in loop electrosurgical excision procedure (LEEP) specimens of patients with colposcopic directed biopsy-confirmed CIN 2-3.Methods:Two hundred and eighty patients with colposcopic directed biopsy-confirmed CIN 2-3 who subsequently underwent LEEP were enrolled in the retrospective study. Related clinical data were collected to determine the predictors of CIN 1 or less in LEEP specimens.Results:CIN 1 or less in LEEP specimens was found in 71 (25.4%) of 280 patients. Multivariate logistic regression analyses demonstrated that nulliparity [OR (95% CI) = 3.375 (1.245-9.150)], low grade Papanicolaou (Pap) results [OR (95% CI) = 6.410 (2.877-14.280)] and low grade colposcopic impression [OR (95% CI) = 16.506 (5.844-46.632)] were significant risk factors of having CIN 1 or less in LEEP specimens. Neither persistent nor recurrent CIN 2-3 was detected in 71 patients who had CIN 1 or less in LEEP specimens. However, persistent or recurrent CIN 2-3 developed in 3 out of 209 (1.4%) patients with CIN 2-3 found in LEEP specimens.Conclusion:Approximately 25% of patients with CIN 2-3 in colposcopic directed biopsy specimens had CIN 1 or less found in LEEP specimens. Predicting factors of having CIN 1 or less in LEEP specimens were nulliparity, low grade Pap results and low grade colposcopic impression.

The Value of Partial HPV Genotyping After Conization of Cervical Dysplasias.

In this retrospective study partial genotyping of human papilloma viruses (HPV) using the Abbott RealTime HighRisk HPV Test (RealTime) was compared with simple HPV detection (Qiagen Hybrid Capture 2 Test; hc2) for recurrence prediction at the first follow-up examination after conization of cervical intraepithelial neoplasia (CIN). 144 women who had undergone conization for CIN between January 2007 and December 2013 were included. HPV status was determined preoperatively and at first follow-up using hc2 in 103 women and RealTime in 41 women. Recurrent or persistent CIN was assumed when CIN2+ was confirmed histologically or on comparable cytology findings. Of the 144 women with complete data 12 (8.3%) had a recurrence after conization. HPV persistence at follow-up correlated significantly with recurrence (hc2: p = 0.003; RealTime: p = 0.003) and both sensitivity and specificity were high (hc2 = 100 and 78.4% respectively; RealTime = 75.0 and 83.9%). Whereas isolated HPV testing had a relatively low positive predictive value for recurrence (hc2 16%; RealTime 54.5%), this rose to 80% with HPV 16 detection at follow-up. At follow-up after conization of CIN the combination of high risk HPV detection and partial genotyping of HPV16 constitutes excellent diagnostic criteria for recurrence/persistence of CIN.

Small Bowel Obstruction After Vaginal Hysterectomy with Bilateral Salpingo-oophorectomy

Background: Removal of adnexa at the time of vaginal hysterectomy (VH) is a feasible procedure in properly selected patients. Small bowel obstruction was not found to be reported as a complication of this procedure. Case: A 61-year-old woman underwent a VH with bilateral salpingo-oophorectomy (BSO) for persistent cervical intraepithelial neoplasia grade 3. On postoperative day 7 she presented with small bowel obstruction that did not resolve with conservative management. During the repeat operation, a hematoma was visualized at the right pelvic side wall where ovarian vessels had been ligated with adhesion to the terminal ileum. Results: The small bowel stuck to the hematoma was released, and the patient underwent an appendectomy. The dilated small bowel was emptied into the stomach and aspirated via nasogastric tube. The patient tolerated the procedure and had an uneventful postoperative course. Conclusions: Small bowel obstruction is a rare complication of VH with BSO, but can occur in association with hematoma formation on the pelvic side wall at the time of the surgery. (J GYNECOL SURG 28:372)

A prospective study of human papillomavirus (HPV) testing to resolve uncertainty in colposcopy

UK colposcopy services are seeing increased workloads, a large proportion of which are follow-up appointments. The English Cervical Screening Programme HPV Special Interest Group identified five subcategories of colposcopy clinic patients who often require prolonged follow-up regimes for low-grade abnormalities. Human papillomavirus (HPV) testing has a high negative predictive value, meaning that HPV-negative women are at very low risk of underlying disease. Our objectives were to quantify the number of HPV-negative women in each study subcategory and to evaluate the number who could potentially be discharged from colposcopy on the basis of their results. Four colposcopy clinics prospectively identified women according to five categories over 12 months. All women underwent cytological testing and high-risk HPV (hrHPV) testing using the Hybrid Capture 2 test. Management outcomes and decisions based on a knowledge of the HPV status were recorded. Data available on 755 women showed that 422/755 (55.9%) and 260/755 (34.4%) had persistent cervical intraepithelial neoplasia grade 1 (CIN1) (Category 1) or a minor abnormality following treatment (Category 2), respectively. In Categories 1 and 2, 51.7% and 60.2%, respectively, were hrHPV negative. The rates with biopsies of CIN2 or worse (CIN2+) across the two categories were 3/355 (0.8%) and 21/291 (7.0%) for hrHPV-negative and hrHPV-positive women, respectively. The incorporation of hrHPV testing within organized cervical screening programmes has been widely accepted. hrHPV testing for the clinical scenarios outlined in this study detects women who are hrHPV negative and therefore at low risk of underlying disease, potentially reducing anxiety and inconvenience for women and costs to colposcopy services.

C-LETZ versus large loop excision of the transformation zone for the treatment of cervical intraepithelial neoplasia: a randomized controlled trial

To compare large loop excision of the transformation zone (LLETZ) with contour-loop excision of the transformation zone (C-LETZ) in management of cervical intraepithelial neoplasia (CIN) with respect to number of specimens obtained, weight of specimen, surgical margin, treatment time, and morbidity associated with those procedures. Women were randomly allocated to receive LLETZ or C-LETZ. Inclusion criteria were the following circumstances: (1) presence of biopsy-proved CIN 2/3, (2) persistent biopsy-proved CIN 1, (3) discrepancy between cytology and histology, or 4) an endocervical curettage was positive. Ninety-eight women were eligible for the study. Mean weight of specimens in C-LETZ group was significantly more than LLETZ group (4.35 ± 1.39 vs. 3.55 ± 1.48 g, p = 0.007). Duration of treatment were similar in both groups (p = 0.39). After multiple logistic regressions were analyzed, C-LETZ was more likely to result in a single pathologic specimen (76 vs. 29.16 %, p < 0.001; adjusted RR 8.33, CI 3.23-21.47). There was no statistical significant difference in the frequency of positive margins between the groups (40 vs. 39.5 %, p = 0.64; adjusted RR 1.27, CI 0.46-3.50). The morbidity associated with those procedures was not different between the two groups. C-LETZ has a clear clinical benefit in term of a higher rate of a single pathologic specimen. It removes more cervical tissue than LLETZ. The incidence of incomplete excision and complication seem to be similar in both groups.

Risk Factors for Persistent Cervical Intraepithelial Neoplasia Grades 1 and 2

: This study examines risk factors for persistent cervical intraepithelial neoplasia (CIN) and examines whether human papillomavirus (HPV) testing predicts persistent lesions. : Women with histologically diagnosed CIN 1 or CIN 2 (n = 206) were followed up every 3 months without treatment. Human papillomavirus genotyping, plasma levels of ascorbic acid, and red blood cell folate levels were obtained. Cervical biopsy at 12 months determined the presence of CIN. Relative risk (RR) was estimated by log-linked binomial regression models. : At 12 months, 70% of CIN 1 versus 54% of CIN 2 lesions spontaneously regressed (p < .001). Levels of folate or ascorbic acid were not associated with persistent CIN at 12 months. Compared with HPV-negative women, those with multiple HPV types (RRs ranged from 1.68 to 2.17 at each follow-up visit) or high-risk types (RRs range = 1.74-2.09) were at increased risk for persistent CIN; women with HPV-16/18 had the highest risk (RRs range = 1.91-2.21). Persistent infection with a high-risk type was also associated with persistent CIN (RRs range = 1.50-2.35). Typing for high-risk HPVs at 6 months only had a sensitivity of 46% in predicting persistence of any lesions at 12 months. : Spontaneous regression of CIN 1 and 2 occurs frequently within 12 months. Human papillomavirus infection is the major risk factor for persistent CIN. However, HPV testing cannot reliably predict persistence of any lesion.

Cigarette smoke stimulates VEGF-C expression in cervical intraepithelial neoplasia (CIN) 1 and 2 lesions

Vascular endothelial growth factors (VEGFs) are involved in angiogenesis, but molecular links to the most important etiological agents, human papillomavirus (HPV) and smoking, need to be clarified. Archival samples at the first diagnosis of 64 cervical intraepithelial neoplasia grade 1 or 2 (CIN 1/2) lesions were examined immunohistochemically using anti-VEGF-C and anti-Ki-67 antibodies. HPV types were identified from cervical samples by restriction fragment length polymorphism, which has been shown to identify at least 26 types of genital HPVs. Follow-up data were available for all patients with CIN lesions. Cervical intraepithelial neoplasia lesions regressed in 47 cases and were persistent in 17 cases. Twenty-two smokers, 8 former smokers, and 34 non-smokers were enrolled in the study. The median observation period was 52.3 months. Significantly higher VEGF-C expression was observed in 8 smokers with persistent CIN persistence (49.0 ± 16.6%, P < 0.01), whereas no significant difference was observed in Ki-67 expression. The median time to regression was significantly longer in the 10 smokers with high VEGF-C expression (48.3 months, P = 0.030) than that in the others. HPV was detected in 56 of the 64 cases. Thirty-two patients had high-risk HPV, 13 had intermediate-risk HPV, and 2 had low-risk HPV. No significant difference was observed among the HPV risk groups in both average Ki-67 and VEGF-C expression. These findings suggest that VEGF-C may play an important role in cigarette smoking-associated cervical carcinogenesis.

Regeneration of cervix after excisional treatment for cervical intraepithelial neoplasia: a study of collagen distribution

To study the distribution of collagen in the regenerated cervical tissue after excisional treatment for cervical intraepithelial neoplasia (CIN). Cohort study. A large tertiary teaching hospital in London. Women who underwent repeat excisional treatment for treatment failure or persistent CIN. Eligible women who underwent a repeat excisional treatment for treatment failure, including hysterectomy, between January 2002 and December 2007 in our colposcopy unit were identified by the Infoflex(®) database and SNOMED encoded histopathology database. Collagen expression was assessed using picro-Sirius red stain and the intensity of staining was compared in paired specimens from the first and second treatments. Differences in collagen expression were examined in the paired excisional treatment specimens. A total of 17 women were included. Increased collagen expression in the regenerated cervical tissue of the second cone compared with the first cone was noted in six women, decreased expression was noted in five women, and the pattern of collagen distribution was equivocal in six women. There is no overall change in collagen distribution during regeneration following excisional treatment for CIN.

Type‐specific HPV geno‐typing improves detection of recurrent high‐grade cervical neoplasia after conisation

The aim of this case-control study was to examine if type-specific human papillomavirus (HPV) DNA geno-typing before and after treatment of high-grade cervical intra-epithelial neoplasia (CIN) improves prediction of recurring or persisting CIN 2 or 3 compared with follow-up cytology or high-risk (hr)HPV testing. Women with biopsy-proven recurrence of CIN 2 or 3 (cases) in a follow-up period of at least 24 months after treatment of high-grade CIN were compared with women without recurrence (controls). These cohorts were identified by a database search of the Riatol Laboratoria (Antwerp, Belgium). In a cohort of 823 women treated with conisation for high-grade CIN between January 2001 and December 2007, 21 patients with a histologically proven recurrence of CIN2+ were identified. A group of women (n=42) from the same cohort without recurrence was randomly chosen. We found that hrHPV testing at 6 months post-treatment is significantly more sensitive compared with follow-up cytology (ratio: 1.31, 95% confidence interval (CI): 1.10-1.54), but less specific (ratio: 0.85, 95% CI: 0.81-0.90) to predict failure of treatment. When compared with hrHPV testing, HPV geno-typing is more efficient (equal sensitivity, but higher specificity, ratio: 1.43, 95% CI: 1.280-1.62). When compared with follow-up cytology, HPV geno-typing is more sensitive (ratio: 1.31, 95% CI: 1.10-1.54) and more specific (ratio: 1.22, 95% CI: 1.14-1.36). All women who developed a recurrence tested positive for hrHPV. The negative predictive value in the absence of hrHPV DNA was 100%. Six months after treatment HPV geno-typing is the most sensitive and specific method to predict recurrent or persistent CIN 2-3 in the next 24 months.

Cálculo de prevalencia y riesgo atribuible de los factores de riesgo relacionados con la persistencia o recidiva de neoplasia cervical intraepitelial (CIN)

The present study aimed to determine the prevalence of risk factors associated with treatment failure at diagnosis of cervical intraepithelial neoplasia (CIN), identify the increased risk posed by treatment failure, and define the prototype of high-risk patients with persistent or recurrent CIN with a view to characterizing the percentage of the population with treatment failure.The most prevalent demographic and environmental risk factors in our population were the presence of high-risk human papillomavirus (HR-HPV)-DNA, followed by smoking, multiparity, a history of hormonal contraception, and HIV-immunosuppression.When performing colposcopic study, the following characteristics were found: 53.30% of the patients had multiple lesions, size was greater than 2cm in 30.00% of patients and major changes were found in the area of transformation in 49.51% of the total.After completing the study, the results were as follows: cure was achieved in more than 90%, persistence was found in 4.35% and recurrence occurred in 1.8%. These results indicate that there are common risk factors associated with treatment failure, including the persistence of HR-HPV after treatment and poor immune response. The remaining factors were unevenly distributed among patients with CIN-I and CIN-II-III, suggesting that these patients constitute two distinct populations with specific risk factors.

Cytological Follow-up of Women Older than 50 Years With High-Grade Cervical Smear Treated by Large Loop Excision

To evaluate cytological surveillance for women older than 50 years, to detect recurrent or residual disease after treatment of cervical intraepithelial neoplasia by loop excision. Women undergoing a large loop excision for high-grade squamous intraepithelial lesion or glandular cytological abnormalities during a period of 4 years (2000-2003) were identified from the colposcopy database. Women younger than 50 years or with a history of previous loop excision were excluded. Clinical data, histology, and follow-up cytology results for up to 2 years after treatment were collected. Eighty-nine patients were identified. Age of the women ranged from 51 to 66 years, with a median of 51.5 years. Thirty-two (36%) had severe dyskaryosis, 53 (60%) had moderate dyskaryosis, and 4 (4%) had glandular abnormalities on cervical cytology before the loop biopsy. Cervical intraepithelial neoplasia (CIN) 2,3 and glandular abnormalities, CIN 1, and no abnormalities were found in 50 (56%), 18 (20%), and 19 (22%) loop specimens, respectively. Invasive disease was found in 2 (2%) cases. They were excluded from further analysis. The lesion was completely excised in 58 (65%) and incompletely excised in 23 (26%) patients. It was not possible to comment on the margin status in 8 (9%) cases. These were excluded from further analysis. Of the 23 women who had margins involved, 8 (35%) had ectocervical, 12 (52%) had endocervical, and 3 (13%) had both margins involved. All women had follow-up cervical smears at the cytology clinic. At 6-month follow-up, 3 patients had persistent CIN and 4 had borderline changes on cervical smears. At 2 years follow-up, 3 patients had high-grade squamous intraepithelial lesion abnormalities, 2 of whom had clear margins at their loop biopsy earlier.Twenty percent of the women with positive endocervical margins on loop excision needed further treatment for residual or persistent disease on follow-up. Overall, 4 (5%) of the 79 patients who had a loop biopsy went on to have cytological abnormalities suggestive of persistent/residual disease needing further treatment. Cytological surveillance for post-loop biopsy follow-up seems to be a good option for detecting residual disease in this high-risk group of patients.

Natural history of cervical intraepithelial neoplasia during pregnancy

It is uncertain whether pregnancy influences the natural history of cervical intraepithelial neoplasia (CIN). Our aim was to evaluate the evolution of CIN in pregnant women. Prospective study. Department of Obstetrics and Gynaecology, University of Insubria, Italy. Women with histological CIN during pregnancy. Between 2003 and 2007, women with an abnormal Pap-smear during pregnancy underwent colposcopy. Patients with histological CIN were followed during pregnancy with colposcopy every 8 weeks and post-partum evaluation was scheduled 3-6 months after delivery. Women with post-partum histological diagnosis of CIN 2-3 underwent conization. To understand the impact of pregnancy on the evolution of CIN, women with CIN 1 discovered during pregnancy were compared to a group of non-pregnant fertile patients with first diagnosis of CIN 1. A total of 78 women were included: 36 (46.2%) with CIN 2-3 and 42 (53.8%) with CIN 1. In women with CIN 2-3, no invasion was suspected during pregnancy and at post-partum evaluation, no invasive or microinvasive cancer, and 19 (52.7%) persistent CIN 2-3, and 17 (47.3%) regressions were diagnosed. In the group of CIN 1, we recorded six (14.3%) progressions to CIN 2-3, seven (16.6%) persistent CIN 1 and 29 (69%) regressions. The control group of non-pregnant women had a lower regression rate (37/76: 48.7%) in comparison to pregnant women (p=0.03). Expectant management for CIN 2-3 diagnosed during gestation is safe. When discovered during pregnancy, CIN 1 has a significantly higher tendency to spontaneous regression in comparison to non-pregnant condition.

Photodynamic therapy of cervical intraepithelial neoplasia with hexaminolevulinate

CIN is a disease of women in their reproductive years, and treatment includes excisional techniques with increased risk of preterm deliveries. Photodynamic therapy (PDT) using topical precursor of photoactive porphyrins may be a non-invasive alternative with minimal side effects. This study assessed the feasibility and response rate of PDT with hexaminolevulinate (HAL) in cervical intraepithelial neoplasia (CIN) and human papillomavirus (HPV) infection. Twenty four patients with a CIN 2 or 3 or a persistent CIN 1 and a positive high-risk HPV-DNA test were included. Each patient had gynaecologic examination including cervical cytology, HPV DNA testing, colposcopy and biopsy. Ten milliliters of HAL-thermogel (10 mM) were topically applied to the cervix for 3-5 hours, followed by 1,000 seconds of illumination of both ecto- and endocervical canal with red coherent light (wave length 633 nm) using a PDT laser and a special light catheter. Follow-up examinations were carried out after 3 (cytology, colposcopy, HPV DNA testing, and if needed re-PDT) and 6 months. Seven, 10, and 7 patients had a CIN 1, 2, or 3, respectively. Treatment could be accomplished in all cases and no severe side effects were encountered. Fifteen out of the 24 patients had a complete response (15/24 = 63%) and a HPV remission 6 months after 1-3 treatments. The remission rates were 71%, 50%, and 71% for CIN 1, 2 and 3. HAL PDT seems to be a non-invasive, repeatable procedure for CIN and cervical HPV infection with minimal side effects which can be easily performed on outpatient basis.

Cervical Cancer Precursors, Diet and Bitter Taste (6-n-propylthiouracil ‘PROP’) Receptors~!2008-02-19~!2008-05-09~!2008-06-12~!

Prior studies suggest that 6-n-propylthiouracil (PROP) taste responsiveness is linked with reduced preferences for sweet and high-fat foods, lower adiposity, and favorable plasma lipid profiles. We hypothesize that women with more severe and persistent cervical intraepithelial neoplasia (CIN) have a greater sensitivity to PROP. To measure this, women with CIN II or III submitted a DNA blood sample and a food frequency questionnaire. Out of the samples tested, thirty- eight (47%) were classified as nontasters (AV) and 36 (44%) were classified as tasters (PA). There were no significant differences (p<0.05) between the taster groups with respect to demographic variables or food frequency data. Women with CIN II at baseline were significantly (p<0.003) more likely to clear the disease than women with CIN III at baseline. Genetic markers of PROP may indicate the likelihood of a woman's acceptance of bitter foods, but had no association with food consumption, body mass index, and persistence of CIN.