Treatment Of Squamous Intraepithelial Lesions Research Articles

Temporal composition of the cervicovaginal microbiome associates with hrHPV infection outcomes in a longitudinal study

BackgroundPersistent infections with high-risk human papillomavirus (hrHPV) can cause cervical squamous intraepithelial lesions (SIL) that may progress to cancer. The cervicovaginal microbiome (CVM) correlates with SIL, but the temporal composition of the CVM after hrHPV infections has not been fully clarified.MethodsTo determine the association between the CVM composition and infection outcome, we applied high-resolution microbiome profiling using the circular probe-based RNA sequencing technology on a longitudinal cohort of cervical smears obtained from 141 hrHPV DNA-positive women with normal cytology at first visit, of whom 51 were diagnosed by cytology with SIL six months later.ResultsHere we show that women with a microbial community characterized by low diversity and high Lactobacillus crispatus abundance at both visits exhibit low risk to SIL development, while women with a microbial community characterized by high diversity and Lactobacillus depletion at first visit have a higher risk of developing SIL. At the level of individual species, we observed that a high abundance for Gardnerella vaginalis and Atopobium vaginae at both visits associate with SIL outcomes. These species together with Dialister micraerophilus showed a moderate discriminatory power for hrHPV infection progression.ConclusionsOur results suggest that the CVM can potentially be used as a biomarker for cervical disease and SIL development after hrHPV infection diagnosis with implications on cervical cancer prevention strategies and treatment of SIL.

Anal Dysplasia Screening in People Living with HIV: Long-Term Follow-Up in a Large Cohort from Northwest Spain.

Anal squamous cell carcinoma (SCC) is not a common disease in the general population, although its incidence is higher in people living with human immunodeficiency virus (PLWH). Anal SCC is caused by human papillomavirus (HPV) infection and arises from premalignant lesions termed squamous intraepithelial lesions (SILs). SIL surveillance programs are based on the early detection and treatment of SILs, especially those with a higher risk of transforming into cancer. An anal surveillance program has been under development in our institution since 2011. In this context, we performed a retrospective cohort study at the anal dysplasia unit of Álvaro-Cunqueiro Hospital (Spain). Epidemiological and clinical data were gathered from our Infectious Diseases Sample Collection (an open sample cohort including PLWH) from January 2011 to January 2022. A total of 493 PLWH were considered, 122 (24.7%) of whom were diagnosed with anal dysplasia at baseline, including 2 cases of anal SCC. Briefly, most of individuals were young men (median age, 38 years old) born in Spain (76%), whose vaccination rate before their inclusion in the program was scarce (<3%). Throughout the study period, 81 (16.4%) cases were diagnosed with high-grade squamous-intraepithelial lesions (HSILs) and 3 with anal SCC. At the baseline, severe immunosuppression (i.e., nadir CD4+ lymphocyte count below 200 cell/μL), and prior diagnosis of condyloma acuminata were more frequent within the group with SILs. Conversely, the baseline CD4+ lymphocyte count was similar among both groups. HPV-16 was related to a higher risk of HSILs (odds ratio: 2.76). At the end of the follow-up, 385 PLWH had been retained in care; one patient had died of anal cancer. Anal dysplasia was common (25% of cases), especially among patients infected by HPV-16, diagnosed with condyloma acuminata, and who were severely immunosuppressed. HPV-16 was the main risk factor for the presentation of HSILs.

Comparative study of topical 5-aminolevulinic acid photodynamic therapy and surgery for the treatment of vulvar squamous intraepithelial lesion

BackgroundVulvar squamous intraepithelial lesion (SIL) is a precursor lesion of vulvar squamous cell carcinoma. The current clinical treatments for vulvar SIL cause damage to the vulvar structure, chronic pain and psychological distress. Topical 5-aminolevulinic acid photodynamic therapy (ALA-PDT) is a novel, non-invasive therapy for intraepithelial lesions. The objective of this study was to compare the clinical efficacy and safety of ALA-PDT with local surgical resection for vulvar SIL. MethodsA total of 56 patients with vulvar SIL were enrolled in this retrospective study. Among them, 16 patients received local resection and 40 patients received ALA-PDT. HPV genotyping and ThinPrep cytologic test (TCT) were used to evaluate treatment efficacy. In addition, colposcopy-directed biopsy was performed in all patients at 3-month follow-up and in patients with positive high-risk human papillomavirus (HR-HPV) and/or abnormal TCT results during the follow-up. ResultsAt 3-month follow-up and in HSIL group the complete remission (CR) rate of the ALA-PDT group and surgery group was 90.6% (29/32) and 87.5% (14/16) (P = 1.000), respectively. The HPV clearance rate of the ALA-PDT group and surgery group was 45.2% (14/31) and 43.8% (7/16) (P = 0.927), respectively. The average numbers of ALA-PDT treatments were 5.34 for HSIL patients and 4.88 for LSIL patients, respectively. The CR rate of HSIL patients and LSIL patients was 90.6% (29/32) and 75.0% (6/8) (P = 0.550), respectively. The HPV clearance rate of HSIL patients and LSIL patients was 45.2% (14/31) and 37.5% (3/8) (P = 1.000), respectively. The ALA-PDT group showed similar clinical efficacy and milder adverse effects compared with the surgical group. ConclusionALA-PDT showed similar clinical efficacy as surgery in the treatment of vulvar SIL, but with milder adverse effects and maintaining the integrity of the vulvar structure.

Terminology for cone dimensions after local conservative treatment for cervical intraepithelial neoplasia and early invasive cervical cancer: 2022 consensus recommendations from ESGO, EFC, IFCPC, and ESP.

Local cervical treatment for squamous intraepithelial lesion (SIL) or cervical intraepithelial neoplasia (CIN) removes or ablates a cone-shaped or dome-shaped part of the cervix that contains abnormal cells. This Series paper introduces the 2022 terminology for cone dimensions after local conservative treatment for SIL, CIN, or early invasive cervical cancer. The terminology was prepared by the Nomenclature Committee of the European Society of Gynaecologic Oncology, the European Federation for Colposcopy, the International Federation of Cervical Pathology and Colposcopy, and the European Society of Pathology. Cone length should be tailored to the type of transformation zone. Treatment of SIL or CIN is associated with an increased risk of preterm birth, which escalates with increasing cone length. There is a lack of agreement regarding terms used to report excised specimen dimensions both intraoperatively and in the pathology laboratory. Consensus is needed to make studies addressing effectiveness and safety of SIL or CIN treatment comparable, and to facilitate their use to improve accuracy of antenatal surveillance and management. This Series paper summarises the current terminology through a review of existing literature, describes new terminology as agreed by a group of experts from international societies in the field of cervical cancer prevention and treatment, and recommends use of the new terminology that will facilitate communication between clinicians and foster more specific treatment guidelines that balance obstetrical harm against therapeutic effectiveness.

Impact of timing of antiretroviral therapy initiation on survival of cervical squamous intraepithelial lesions: a cohort analysis from South Africa

To determine factors that influence excision treatment outcome and recurrence of cervical squamous intraepithelial lesions (SIL) in women living with HIV infection, we analysed 1848 women who underwent excision treatment of cervical SIL at Tygerberg Hospital, Cape Town, South Africa. We compared treatment failure defined as presence of cervical intraepithelial neoplasia (CIN) I (presence of CIN I or higher at first follow-up after excision treatment) and post-excision recurrence of lesions (at one year or later) between women of HIV-positive, -negative or unknown status and examined factors associated with excision treatment outcome and recurrence. HIV-infected women experienced higher treatment failure than uninfected women (53.8% versus 26.9%, P < 0.001). At treatment failure, more HIV-infected women had low-grade squamous intraepithelial lesion (LSIL) compared with uninfected women (64.9% versus 37.3%, P < 0.001). Treatment failure did not differ with the type of excision used in HIV-infected women. HIV-infected women were more likely to experience recurrence of lesions after excision treatment than uninfected women (hazard ratio 1.95, 95% confidence interval [CI] 1.59-2.39; P < 0.001). Antiretroviral therapy (ART) initiated before excision biopsy had a strong protective effect against recurrence (hazard ratio 0.70, 95% CI 0.55-0.89; P = 0.006). Our data suggest that women with cervical SIL initiated on ART earlier may be expected to have better long-term excision treatment outcome. Close follow-up should be maintained after cervical excision treatment, especially in a setting of high HIV prevalence.

Multiple levels on LLETZ biopsies do not contribute to patient management

Cervical large loop excision of the transformation zone (LLETZ) specimens are performed both to treat and to diagnose or exclude cervical pre-neoplasia. Examination of these specimens forms a significant part of the routine histological work load of the pathologist, yet histological confirmation of squamous intraepithelial lesion (SIL) or completeness of excision, does not alter the treatment of SIL. When the LLETZ procedure is done, the treatment is complete, the dysplasia having been subject to excision as well as diathermy during the procedure. In this study, records of 1139 women who underwent LLETZ treatment for SIL were examined. The grade of SIL present and the margin status were extracted from histology reports and linked to post-LLETZ follow-up cytology and histology, for a period of 2 years. SIL recurrence in women with high grade (HG-SIL), low grade SIL (LG-SIL) and normal LLETZ biopsy results was not significantly different. There was no significant difference between the recurrence rates of HG-SIL and LG-SIL with SIL at margins compared to SIL clear of margins. Pathologists spend significant time examining multiple levels of LLETZ biopsies, grading SIL, determining margins and trying to find SIL in 'normal' LLETZ biopsies. None of this affects the subsequent follow-up. The most useful data the pathologist can provide is whether invasion is present or not. Pathological effort should be directed to examining multiple levels of those with HG-SIL to find invasion, rather than spending time looking at multiple levels of normal or LG-SIL LLETZ biopsies.

Progress and Pitfalls in Defining the Influence of Highly Active Antiretroviral Therapy on Human Papillomavirus–Associated Cervical Disease

Progress and Pitfalls in Defining the Influence of Highly Active Antiretroviral Therapy on Human Papillomavirus–Associated Cervical Disease

Prevalence and severity of cervical squamous intraepithelial lesion in a tertiary hospital in northern Tanzania

Cervical cancer is the second most common cancer in women worldwide and the leading cause of cancer deaths in Tanzanian women. Prevention of cervical cancer relies on the detection and treatment of Squamous Intraepithelial Lesion (SIL), a premalignant disease stage. Worldwide there are overwhelming reports associating SIL and HIV infection, however in Tanzania such reports are limited. A cross-sectional hospital-based descriptive study was conducted to determine the prevalence and severity of SIL in 234 HIV seropositive and seronegative women aged 18-68 years old at Kilimanjaro Christian Medical Centre in northern Tanzania. A structured questionnaire was used to collect sociodemographic data. In addition, blood was collected for rapid HIV antibody testing and CD4+ T-lymphocyte counts to associate with prevalence and severity of SIL from the cervical smear collections. A total of 214 subjects had smear results regarded as valid for interpretation, of which 46.3% were HIV seropositive. Overall rate of SIL was 17%. Proportion of SIL among HIV seropositive subjects was 32% versus 4% in seronegative subjects (OR = 13.3, 95% CI = 4.2-46.4). Low CD4+ T-lymphocyte cell count was associated with higher prevalence of SIL (P = 0.001). The relationship between CD4+ T-lymphocyte cell counts and the severity of cervical SIL was significant (P = 0.007). Marital status and number of lifetime sex partners were risk factors significantly associated with SIL (P = 0.004 and 0.005, respectively). SIL was not associated with age, education level, parity or age at sex debut. The prevalence and severity of cervical SIL was significantly associated with HIV infection and immunologic disease progression. These findings underscore the need for HIV screening among women with SIL, and the need for cervical cancer screening in HIV-infected women. Marital status and number of lifetime sex partners were significant risk factors associated with SIL.

Effect of HIV Infection on Atypical Squamous Cells of Undetermined Significance

Detection of atypical squamous cells of undetermined significance (ASCUS) is a cervical cytologic finding that is suggestive but not definitive of squamous intraepithelial lesions (SILs). We examined the risk, characteristics, and progression of ASCUS in women with and without human immunodeficiency virus (HIV) infection. Cervical Papanicolou (Pap) test and colposcopy data were obtained at the first 10 semiannual visits for the HIV Epidemiology Research study of 774 HIV-infected and 480 demographically similar, HIV-uninfected women in the United States. Multiple logistic regression models and Cox proportional hazards models were utilized. ASCUS was more common among HIV-infected women (odds ratio [OR], 1.6 [95% confidence interval {CI}, 1.3-2.0] to 2.6 [95% CI, 1.9-3.6]) after adjustment for human papillomavirus (HPV) infection and other risk factors (e.g., race, condyloma, and prior Pap test result). Among women with normal Pap test results at enrollment, the cumulative incidence of ASCUS was 78% among HIV-infected women and 38% among HIV-uninfected women. HIV-infected and HIV-uninfected women with ASCUS did not differ by prevalence of indices of inflammation (inflammation on Pap test and leukocytes on cervical gram stain). HPV infection, including high risk types, was more common among HIV-infected women with ASCUS. Among women with ASCUS, 60% of HIV-infected and 25% of HIV-uninfected women developed SILs (P < .01). Compared with HIV-infected women with higher CD4+ lymphocyte counts, HIV-infected women with CD4+ lymphocyte counts < 200 cells/microL were more likely to present subsequently with a SIL detected by Pap test (OR, 1.7; 95% CI, 0.8-3.6). Higher risk of SIL following the appearance of ASCUS among HIV-infected women, especially women with low CD4+ lymphocyte counts, supports the need for follow up with colposcopy and histologic examination, as indicated, to allow early detection and treatment of SIL.

Treatment outcomes for squamous intraepithelial lesions

Objective: To assess the effectiveness of cone biopsy, cryotherapy, laser ablation and the loop electrosurgical procedure in the treatment of squamous intraepithelial lesions. Method: Systematic review of randomized controlled trials in subjects who underwent treatment of low- and high-grade squamous intraepithelial lesions with these modalities. Main outcome measures included the following: percent resolution and persistence of a lesion and notable complications for each procedure. Result: Pooled rates of resolution for low-grade, high-grade, or combined squamous intraepithelial lesions were similar across the different treatment modalities (range 85.2–94.7%), with substantial overlap among the 95% confidence intervals. Significant hemorrhage occurred most frequently in subjects who received cone biopsy (4.6%) (95% CI: 2.15, 6.99), followed by laser ablation (1.75%) (95% CI: 0.70, 2.81), and LEEP (1.35%) (95% CI: 0.24, 2.47). No hemorrhages were reported among subjects who received cryotherapy. Study sample sizes were relatively small. There were no reported cases of progression to invasive cancer, but duration of follow-up (median follow-up time for all eligible studies=12 months) was not sufficient to evaluate long-term outcomes. Conclusions: There were no substantive differences in outcomes regarding persistence and resolution in the treatment of squamous intraepithelial lesions for subjects receiving cone biopsy, cryotherapy, laser ablation, or LEEP.

A Randomized Clinical Trial of Cryotherapy, Laser Vaporization, and Loop Electrosurgical Excision for Treatment of Squamous Intraepithelial Lesions of the Cervix

Mitchell, Michele Follen; Tortolero-Luna, Guillermo; Cook, Elise; Whittaker, Lori; Rhodes-Morris, Helen; Silva, Elvio Author Information

A Randomized Clinical Trial of Cryotherapy, Laser Vaporization, and Loop Electrosurgical Excision for Treatment of Squamous Intraepithelial Lesions of the Cervix

In Brief Objective To compare cryotherapy, laser vaporization, and loop electrical excision for treatment of squamous intraepithelial lesions (SILs). Methods Women at least 18 years old with biopsy-proven SIL, negative pregnancy tests, negative findings on endocervical curettage, satisfactory colposcopy examinations, and congruent Papanicolaou smear and biopsy results were assigned randomly to treatment after stratification by SIL grade, endocervical gland involvement, and lesion size; they were evaluated 1, 4, 8, 12, 16, 20, and 24 months after treatment. Data were analyzed using χ2 statistics, logistic regression analysis, and the Cox proportional hazards model. Results Of 498 patients assigned, 108 were excluded (most because of inadequate follow-up), leaving 390 (139 cryotherapy, 121 laser vaporization, 130 loop excision) for analysis. All were followed 6–37 months (mean 16). There were no statistically significant differences in complications, persistence (disease present less than 6 months after treatment), or recurrence (disease present more than 6 months after treatment). Risk of persistent disease was higher among women with large lesions (risk ratio [RR], 18.9; 95% confidence interval [CI], 3.2, 110.6). Recurrence risk was higher among women aged 30 years and older (RR, 2.1; 95% CI, 1.2, 4.3), those with human papillomavirus type 16 or 18 (RR, 2.1; 95% CI, 1.1, 4.0), and those who had had prior treatment (RR, 2.1; 95% CI, 1.1, 3.9). Conclusion The data support a high success rate with all three modalities. No significant difference in success rates was observed between the three treatments in our population. Additional attention and research should be directed toward the higher risk patients identified above. Cryotherapy, laser vaporization, and loop electrosurgical excision are equally effective for treating squamous intraepithelial neoplasia of the cervix.

A randomized clinical trial of cryotherapy, laser vaporization, and loop electrosurgical excision for treatment of squamous intraepithelial lesions of the cervix

Objective: To compare cryotherapy, laser vaporization, and loop electrical excision for treatment of squamous intraepithelial lesions (SILs). Methods: Women at least 18 years old with biopsy-proven SIL, negative pregnancy tests, negative findings on endocervical curettage, satisfactory colposcopy examinations, and congruent Papanicolaou smear and biopsy results were assigned randomly to treatment after stratification by SIL grade, endocervical gland involvement, and lesion size; they were evaluated 1, 4, 8, 12, 16, 20, and 24 months after treatment. Data were analyzed using χ 2 statistics, logistic regression analysis, and the Cox proportional hazards model. Results: Of 498 patients assigned, 108 were excluded (most because of inadequate follow-up), leaving 390 (139 cryotherapy, 121 laser vaporization, 130 loop excision) for analysis. All were followed 6–37 months (mean 16). There were no statistically significant differences in complications, persistence (disease present less than 6 months after treatment), or recurrence (disease present more than 6 months after treatment). Risk of persistent disease was higher among women with large lesions (risk ratio [RR], 18.9; 95% confidence interval [CI], 3.2, 110.6). Recurrence risk was higher among women aged 30 years and older (RR, 2.1; 95% CI, 1.2, 4.3), those with human papillomavirus type 16 or 18 (RR, 2.1; 95% CI, 1.1, 4.0), and those who had had prior treatment (RR, 2.1; 95% CI, 1.1, 3.9). Conclusion: The data support a high success rate with all three modalities. No significant difference in success rates was observed between the three treatments in our population. Additional attention and research should be directed toward the higher risk patients identified above.

Conization of the uterine cervix: two different surgical techniques

The treatment of squamous intraepithelial lesions (SIL) of the uterine cervix, associated or not with the human papilloma virus (HPV) infection, represents one of the most important problems today in gynecological oncology. The natural history of invasive squamous cell carcinoma of the uterine cervix demonstrates that the intraepithelial lesion is always present before invasive cancer; we still do not know what causes the change of intraepithelial lesions into invasives. The two grades of SIL (I = low +/HPV infection; II = moderate/severe +/HPV infection) often occur in young women, are related to sexual activity, sexually transmitted diseases, age at first intercourse 1. Because of the young age of the patients and the importance of future fertility, the correct choice of the SIL treatment is very important. SIL at grade I can be treated with several techniques, including diathermy, laser, and criotherapy. None of these methods cause infertility if performed by skilled operators. Grade II SIL requires a complete surgical excision of the lesion, that can be performed using a cold scalpel, electro-surgery or laser 2-6.