High-grade Cervical Dysplasia Research Articles

Diagnostic cervical excision in patients with HPV positivity, cytological abnormalities- and preoperative cervical stenosis

AimThere is currently no protocol for classifying patients with HPV persistence and preoperative stenosis of the cervical canal. This has a significant impact on cytology results, colposcopy results and the possibility of obtaining reliable cervical histology outcomes. Our analysis clearly shows that colposcopy and cytology underestimate the histological results in patients with limited visibility due to the presence of a type 3 transformation zone (TZ). Our analysis revealed a significant discrepancy between the colposcopy and cytology results and the histological outcomes. Insufficient colposcopy led to the underdiagnosis of dysplastic lesions in patients with a type 3 TZ and cervical stenosis. In the case of repeated cytological abnormalities and inadequate colposcopy examination, it is crucial to perform a diagnostic conization to exclude high-grade dysplastic changes and cervical carcinoma.MethodsWe conducted a retrospective analysis of 1,021 conizations performed in tertiary care hospital in Wolfsburg, Germany between 2014 and 2020. Of these surgical procedures, 89 were diagnostic conizations. In our analysis, we defined diagnostic conization as a procedure performed when there is HPV persistence and repeated cytologic abnormalities in combination with a type 3 TZ, and when it is not possible to retrieve a relevant cervical histology sample.ResultsIn this period, 8.7% of all conizations were diagnostic excisions. We found histological abnormalities in 48 of 89 patients (53.9%). The histological examination of the excised cone revealed high-grade cervical intraepithelial neoplasia (CIN/HSIL) in 9 patients (10.1%) and CIN 2+ (HSIL) in 23 out of the 89 patients (25.8%). Two cases of early-stage cervical carcinoma (FIGO IA1 and FIGO IA2) were confirmed (2.3%).ConclusionPatients with cervical stenosis, high-risk HPV persistence and repeated cytological abnormalities are at high risk of undetected high-grade cervical dysplasia. Histologic confirmation must be ensured in this patient consultation and this can be achieved by performing diagnostic excisions.

An analysis of the vaginal microbiota and cervicovaginal metabolomics in cervical lesions and cervical carcinoma

BackgroundTo explore the role of vaginal microbiota and metabolomics in the progression of cervical dysplasia. MethodsThe patient group consists of female patients with low-grade, high-grade cervical dysplasia, and cervical cancer. Normal cervix samples from health volunteers were used as controls. The metabolic fingerprints of cervicovaginal lavage were analyzed using liquid chromatography-mass spectrometry, while the vaginal microbiota was examined through 16S rRNA sequencing. Bioinformatic analysis was adopted to investigate the interplay between hosts and microbes. The vaginal metabolic and microbiota profiles of 90 female patients with cervical dysplasia and 10 controls were analyzed to discover the biological characteristics underlying the progression of cervical cancer. ResultsWe found that Valyl-Glutamate, N, N′-Diacetylbenzidine, and Oxidized glutathione, which were involved in oxidative stress response, were discriminators to distinguish the normal cervix, invasive cervical carcinomas, and CIN3 from others. Cervical carcinoma was characterized by a large variety of vaginal microbes (dominated by non-Lactobacillus communities) compared to the control. These microbes affected amino acid and nucleotide metabolism, producing metabolites with cervical carcinoma and genital inflammation compared to the control group. ConclusionsThis study revealed that cervicovaginal metabolic profiles were determined by cervical cancer, vaginal microbiota, and their interplays. ROS metabolism can be used to discriminate normal cervix, CIN3, and invasive cervical carcinoma.

Association Between Maternal Age and Postpartum Assessment of High-Grade Cervical Dysplasia Diagnosed in Pregnancy [ID 2683560

INTRODUCTION: The incidence of cervical dysplasia in pregnancy is expected to rise as patients delay childbearing. Historical studies have quoted high rates of postpartum regression of lesions diagnosed in pregnancy. We sought to evaluate the relationship between maternal age and postpartum progression, regression, and persistence of high-grade lesions. METHODS: This is a retrospective cohort study of patients with biopsy-proven high-grade dysplasia diagnosed during pregnancy from January 2013 to December 2022. Institutional review board approval was obtained. Only immunocompetent patients with postpartum pathology obtained within 1 year of delivery were included. Definitions based on postpartum pathology were as follows: regression as low-grade or resolved dysplasia, persistence as high-grade dysplasia, and progression as invasive cervical cancer. Results were stratified by maternal age (≤24, 25–29, 30–34, 35+) and data were analyzed using the Cochran–Armitage test. RESULTS: Among our cohort (N=286), 101 (35%) were diagnosed with CIN2, 181 (63%) with CIN3/CIS, and 4 (1%) with HSIL (not otherwise specified) on antepartum cervical biopsy. Average age was 28 (±4.2) years. Postpartum regression rate was 44% for patients aged 24 years or younger, 37% in ages 25–29, 33% in ages 30–34, and 33% in ages 35 or older (P=.174). Persistence was common (55%, 63%, 67%, and 64%, respectively) and apparent progression to cancer was rare, occurring in 1% of patients aged 24 years or younger and in 2.8% of patients 35 or older (P=.68). CONCLUSION: Persistence occurred in over half of patients, regardless of age. Our findings emphasize the importance of postpartum follow-up, and possible cervical excision, in patients with antepartum high-grade dysplasia.

Synoptic Operative Reporting in Cervical Cancer Surgeries: Experience From a Single Oncology Center.

Objective In today's era of highly methodological oncological practices in place, we have a huge database to regulate, and it is foreseeable that a humongous load of information is ahead of us that we need to organize and comprehend. With the advancement in surgical equipment and evolving procedures, we need to store the information in a transferrable, understandable, and systematic way to prevent any ebb in the future. The systematic recording of operative data is even more important for patient management, training, and research. Standardized reporting also helps surgical residents have a better understanding of all aspects of the procedure. This study aims to analyze the synoptic operative reporting in cervical cancer patients from December 2009 to February 2020 in asingle tertiary care center dedicated to providing oncology services to patients. This study will analyze the understandability, volume, and ease of transference of data during the given time period. Methodology The Alberta Cancer Registry was contacted to obtain data from the synoptic operative reports. Synoptic Operative Reports of all the patients operated on cervical cancer from December 2009to February 2020. Results The data were obtained for 574 patients. As many as 463 patients were operated on for stage 1 and 2 cervical cancers and 10 patients for advanced and recurrent cervical cancer. A total of 101 patients were operated on for high-grade cervical dysplasia (HSIL). Adenocarcinoma was the most common histology. Laparotomy was performed in 308 patients, whereas others had laparoscopic procedures. Details of the surgery from the beginning of the incision to closure were recorded. The cervical cancer template consisted of 356 questions. There were separate templates for advanced and early-stage cancer. However, even with the meticulously detailed report, an average of only eight minutes was taken by each user to complete the template. Conclusion The computerized synoptic operative report has an upper hand over the dictated documentation report along with the ease of execution without missing essential substance. Its utility as an educational tool is very promising. Therefore, we encourage other facilities, especially cancer centers, to use synoptic operative reports more extensively not only for cervical cancer surgeries but also for other ones.

Addressing cervical cancer disparities in Texas: Expansion of a community-based prevention initiative for medically underserved populations

Although cervical cancer is preventable, significant disparities exist in access to screening and prevention services. In medically underserved areas (MUAs) of Texas, these rates are 55% higher compared to the remainder of the US. In 2019, we expanded a multicomponent, comprehensive program to improve cervical cancer prevention in partnership with 13 clinics and mobile vans in MUAs of Texas. Our multicomponent intervention program consists of community education and patient navigation coupled with a training/mentoring program for local medical providers to perform diagnostic procedures and treatment for patients with abnormal screening results. Hands-on training courses to learn these skills are coupled with biweekly telementoring conferences using Project ECHO® (Extension for Community Healthcare Outcomes). This program was implemented in 2015 and expanded to other MUAs in Texas in 2019. From March 2019 to August 2022, 75,842 individuals were educated about cervical cancer screening and HPV vaccination. A total of 44,781 women underwent screening for cervical cancer, and 2,216 underwent colposcopy and 264 underwent LEEP. High-grade cervical dysplasia was diagnosed in 658 individuals and invasive cervical cancer in 33 individuals. We trained 22 providers to perform colposcopy and/or LEEP. In addition, 78 Project ECHO telementoring sessions were held with an average of 42 attendees per session, with 72 individual patient cases discussed. Our comprehensive community-based prevention initiative for medically underserved populations has led to a significant number of individuals undergoing cervical cancer screening in MUAs, as well as improved access to colposcopy and LEEP services.

Duration of human papillomavirus persistence and its relationship with recurrent cervical dysplasia.

To evaluate how the duration of human papillomavirus (HPV) persistence influences the risk of developing recurrent high-grade cervical dysplasia (CIN2+). Data of patients with persistent HPV infection (at least at 6 months) after primary conization were extracted from a multi-institutional Italian database, retrospectively. Kaplan-Meier and Cox proportional hazards models were used to evaluate associations between duration of HPV persistence with the 5-year risk of developing recurrent CIN2+. Overall, 545 patients met the inclusion criteria. Positive margins were detected in 160 (29.3%) patients. Overall, 247 (45.3%) and 123 (22.6%) patients had a documented infection from HPV16/18, and other high-risk HPV types. 187 (34.3%), 73 (13.4%), and 40 (7.3%) were diagnosed with persistent HPV infection at 12, 18, and 24 months, respectively. Patients with HPV persistence at 6 months experienced a risk of recurrence of 7.46%. Twelve-month HPV persistence strongly correlates with the risk of developing the recurrent disease (risk of recurrence: 13.1%). While, having HPV persistence >12 months did not correlate with an increased risk of recurrence (hazard ratio: 1.34 (95% confidence interval: 0.78-2.32); P = 0.336, log-rank test). HPV persistence is one of the most important factors predicting the risk of CIN2+ recurrence. The risk of CIN2+ recurrence increased with the increase of HPV persistence for up to 1 year. The persistence of HPV after the first year does not appear as a risk factor.

Abstract 5596: Cell free DNA levels and fragmentation patterns in different liquid biopsy analytes (blood, urine and vaginal fluid) in cervical cancer patients

Abstract Background: Cervical cancer (CC) is the 4th most commonly diagnosed cancer among women, with approximately 528,000 new cases annually. Current screening approaches for this disease have certain limitations; Pap tests require dedicated cytopathology infrastructure, while human papillomavirus (HPV) DNA testing may lead to invasive procedures in patients with transient infection. Liquid biopsy has emerged as a minimally invasive approach to detect and monitor disease progression and treatment response. We and others have previously demonstrated the clinical utility of circulating tumor (ct)DNA to monitor HPV+ cancers. Moreover, cell free (cf)DNA fragmentation patterns have been found to be a biomarker of disease burden. This cfDNA is thought to originate largely as a result of cell death, where small fragments of ~167 bp are associated with apoptosis and larger fragments (>1000 bp) are associated with necrosis. Despite advances in liquid biopsy techniques, little is known about the composition of cfDNA from different analytes in CC patients. Methods: The aim of this study was to compare the presence and composition of cfDNA from different liquid biopsy analytes in patients with CC and high grade cervical intraepithelial neoplasia or dysplasia (CIN/CD). Blood, urine, and vaginal swabs were collected from 20 patients with CC and 9 patients with CIN/CD at the McGill University Health Centre. All samples were centrifuged twice to isolate supernatant. Samples were tested for HPV ctDNA by ddPCR. Analysis of fragment length was performed using the Agilent Bioanalyzer 2100. Dominant fragment was determined as the DNA fragment with the highest concentration, while overall fragment was calculated as the average fragment across all bioanalyzer peaks. Results: HPV16/18 ctDNA was detectable 14/20 CC patients and 2/6 CIN patients, and 0/3 CD patients in plasma, urine, and vaginal swab. Concordance for all sample types tested was seen in 90% of cases. On average, fragment analysis demonstrated 174, 195, and 183 bp dominant small fragments in plasma, urine and vaginal swab, respectively. Plasma samples showed only smaller fragments (range: 168-187 bp). Other analytes displayed a predominance of larger cfDNA, with an overall fragment size of 3996 and 5194 bp in urine and vaginal swab, respectively. Conclusions: HPV-DNA was detectable in all analytes sampled in patients with CC and CIN, with a trend of higher detection in CC samples. The fragmentation patterns of cfDNA varied between patients and within patients across analytes, with larger fragments - likely of necrotic origin - seen only in urine and vaginal swab cfDNA. Smaller fragments - likely related to apoptosis - were seen across all sample types studied. Overall, analysis of fragmentation may provide valuable insight into cfDNA origins in different sample types and provide a novel biomarker for diagnosis and surveillance. Citation Format: Sarah Tadhg Ferrier, Erica Mandato, Alexandra Bartolomucci, Thupten Tsering, Shuk On Annie Leung, Julia Valdemarin Burnier. Cell free DNA levels and fragmentation patterns in different liquid biopsy analytes (blood, urine and vaginal fluid) in cervical cancer patients. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5596.

Outcomes of High-Grade Cervical Dysplasia with Positive Margins and HPV Persistence after Cervical Conization.

The objective of this work is to assess the 5-year outcomes of patients undergoing conization for high-grade cervical lesions that simultaneously present as risk factors in the persistence of HPV infection and the positivity of surgical resection margins. This is a retrospective study evaluating patients undergoing conization for high-grade cervical lesions. All patients included had both positive surgical margins and experienced HPV persistence at 6 months. Associations were evaluated with Cox proportional hazard regression and summarized using hazard ratio (HR). The charts of 2966 patients undergoing conization were reviewed. Among the whole population, 163 (5.5%) patients met the inclusion criteria, being at high risk due to the presence of positive surgical margins and experiencing HPV persistence. Of 163 patients included, 17 (10.4%) patients developed a CIN2+ recurrence during the 5-year follow-up. Via univariate analyses, diagnosis of CIN3 instead of CIN2 (HR: 4.88 (95%CI: 1.10, 12.41); p = 0.035) and positive endocervical instead of ectocervical margins (HR: 6.44 (95%CI: 2.80, 9.65); p < 0.001) were associated with increased risk of persistence/recurrence. Via multivariate analyses, only positive endocervical instead of ectocervical margins (HR: 4.56 (95%CI: 1.23, 7.95); p = 0.021) were associated with worse outcomes. In this high-risk group, positive endocervical margins is the main risk factor predicting 5-year recurrence.

Is the human papillomavirus vaccine effective in preventing high-grade cervical dysplasia in previously unvaccinated women more than 26 years old with low-grade dysplasia?

Cahaba Family Medicine Residency, Birmingham, AL The corresponding author is Austin Klint; [email protected]. The authors declare no conflicts of interest.

Cervical cancer screening in HIV-endemic countries: An urgent call for guideline change

Women living with HIV (WLWH) are at an increased risk of developing HPV-related high grade cervical dysplasia and cervical cancer. Prior World Health Organization (WHO) screening guidelines recommended starting screening at age 30. We assessed characteristics of women diagnosed with cervical cancer to further inform and refine screening guidelines. We prospectively enrolled women diagnosed with cervical cancer from January 2015 to March 2020 at two tertiary hospitals in Gaborone, Botswana. We performed chi-square and ANOVA analyses to evaluate the association between age upon diagnosis and HIV status, CD4 count, viral load, and other sociodemographic and clinical factors. Data were available for 1130 women who were diagnosed with cervical cancer and 69.3% were WLWH. The median age overall was 47.9 (IQR 41.2–59.1), 44.6 IQR: 39.8 – 50.9) among WLWH, and 61.2 (IQR 48.6–69.3) among women living without HIV. There were 1.3% of women aged <30 years old, 19.1% were 30–39 and 37.2% were 40–49. Overall, 20.4% (n = 231) of cancers were in women <40 years. Age of cervical cancer diagnosis is younger in countries with higher HIV prevalence, like Botswana. Approximately 20% of the patients presented with cancer at <40 years of age and would have likely benefited from screening 10 years prior to cancer diagnosis to provide an opportunity for detection and treatment of pre-invasive disease.

Prevalence of anal dysplasia and HPV genotypes in gynecology patients: The ANGY cross-sectional prospective clinical study protocol.

BackgroundHuman Papillomaviruses (HPV) are highly prevalent in the sexually active populations, with a significant burden in terms of health and psychological cost in all class ages. High-risk (HR) HPV genotypes are associated with anogenital dysplasia and cancers, and anal HPV-induced cancer is increasingly observed in women. The interactions of HPV genotype’s between the anus and the cervix, and the subsequent occurrence of dysplasia remains unclear. This clinical study set out to test the hypothesis that risk factors for anal HR-HPV and dysplasia may differ in women with or without cervical dysplasia or in HIV-positive women.MethodsCervical and anal HPV genotypes and cytology testing will be performed prospectively in a cohort of women recruited in a tertiary university hospital in Switzerland. Women will be allocated to three groups: 1) normal previous cervical smear; 2) high-grade cervical dysplasia (H-SIL) at previous cervical smear; 3) HIV+, independently of previous cervical smear result. General inclusion criteria comprised the followings: Female—Age > = 18 years; Satisfactory understanding of French; No objection to HIV testing. Specific inclusion criteria are: Group 1, no past or current gynecological dysplasia and HIV negative; Group 2, Gynecological dysplasia (H-SIL) or carcinoma in situ demonstrated by histology (vulvar, vaginal or cervical) and HIV negative; Group 3: HIV-positive (regardless of viremia or CD4 count) with or without gynecological dysplasia. General exclusion criteria are: Pregnancy; History of anal dysplasia/cancer; Status after pelvic radiotherapy; Absence of anus and anal canal. Estimated prevalences of anal dysplasia are: in group 1, 1% (0–2%); in group 2, 15% (5–27%), and in group 3, 30% (19–45%). With a 10% margin error, a sample size of 120 women per group is required to reach 90% power for detecting statistical significance (unilateral α error of 5%).DiscussionThe primary endpoint is the prevalence of anal and cervical dysplasia, and description of the respective HPV genotypes in each group. The results of this study could improve the standard of screening of cervical and anal dysplasia in women through evidence of concomitant presence of HPV’s and/or dysplasia in anus or cervix to support vaccination for instance. Beginning of recruitment started in September 2016. Results should be presented in end of 2022. Preliminary analysis for first 100 patients reveals that the mean age of the population is 39.6 (± 10.9) years with mean age of first sexual intercourse of 18.5 (± 3.9) years. In this cohort, 12% are vaccinated and 38% having had anal intercourse. Overall, 43% of the studied population had cervical HR-HPV in the studied population, and 53% had normal cytology. Anal LR HPV and HR HP were found in 27.6% and 38.4% of all patients respectively. Eighty percent had normal anal cytology. Groups 1,2 and 3 had a significant difference in terms of age, gestity, parity, age of first sexual intercourse, systematic use of condom, number of cervical LR HPV and HR HPV and abnormal cervical cytologies.Trial registrationThe study was approved by the institutional review board—CER-VD#2015–00200—on the 29th of June 2016 and is registered on the Swiss National Clinical Trials Portal (SNCTP), SNCTP000002567, Registered 29 June 2016, https://www.kofam.ch/en/snctp-portal/study/40742/

Patient Adherence to Follow-Up Recommendations Following Cryotherapy for Treatment of High-Grade Cervical Dysplasia

Objective Determine the rate of patient adherence to follow-up recommendations after cryotherapy for high-grade cervical lesions, and identify patient characteristics associated with adherence to follow-up. Methods This is a retrospective case series from May 2016 to June 2018 of patients who underwent cryotherapy for high-grade dysplasia at a single academic safety-net hospital. Patient demographics and clinical information were abstracted from the electronic medical record. All patients were recommended to follow up with Pap and high-risk human papillomavirus (HPV) testing 12 months after their procedure. The primary outcome was patient adherence to these recommendations. Descriptive statistics and statistical testing were utilized to compare adherence by demographic and clinical characteristics. A multivariable logistic model was used to preliminarily look at potential factors associated with increased odds of adherence. We further described the proportion of follow-up testing among those patients who adhered to recommendations. Results One hundred and forty-three patients met the inclusion criteria. The adherence percentage was 60.1% (95% CI: 51.6, 68.2). Only employment was associated with follow-up among demographic variables reviewed (p=0.039). Of those who were adherent with follow-up, 4.7% (4/86) had high-grade findings on follow-up Pap testing, and 56.9% (49/86) had negative cytology and negative HPV testing. Conclusion Adherence to follow-up recommendations for the following cryotherapy for high-grade dysplasia within our system was poor, and demographic factors were generally not associated with adherence to follow-up. Given these findings, cryotherapy should be used with caution.

S1048 Cervical Cancer Screening for Patients With Inflammatory Bowel Disease: A Tertiary Care Center Experience

Introduction: Evidence has suggested an increased risk of cervical high-grade dysplasia and cancer in females with Inflammatory Bowel Disease (IBD) on immunosuppressive medications. Therefore, gastroenterology societies have recommended annual cervical cancer screening for this IBD specific population. This is ultimately performed to improve earlier detection of cervical cancer in high-risk patients. Methods: A sample of patients were selected from a medical records database at a tertiary care. Inclusion criteria included a confirmed diagnosis of Ulcerative Colitis (UC) or Crohn’s Disease (CD) and an established primary care clinic relationship with the internal medicine residents or non-teaching internists of the same medical center. General Demographics, referrals to Obstetrics/Gynecology, department from where the referrals were placed, performance of the Papanicolaou tests, results of the tests, and the dates of the tests were tabulated and studied. Information relating to the clinical aspects of IBD including current and previous medical therapies was also collected. Results: A total of 30 patients with a diagnosis of IBD receiving biologic therapy were included in the study. 23 patients were cared for in the resident clinic and 7 were followed by non-teaching internists. 9 out of 30 patients had not completed a Papanicolaou test and all of whom were diagnosed with IBD beyond three years of the time of data collection. Of the 21 patients who completed the first Papanicolaou test, 19 had normal results, the remaining 2 had atypical squamous cells of undetermined significance. No further procedures, such as colposcopy or LEEP, were performed in these 2 patients. No statistically significant difference was found in patients receiving their first Papanicolaou test between CD and UC patients. 10 out of the 19 patients with initial normal results completed their second Papanicolaou test, however there was a median of 581.5 days between the two screenings. Only 8 patients completed a third Papanicolaou test. Of the 30 patients, only 6 were referred to Obstetrics/Gynecology, with all these referrals being made by internal medicine physicians. Conclusion: Although the sample size was small, this study does demonstrate a gap in current application of cervical cancer screening guidelines in this high risk IBD population. Ultimately, a follow up study to evaluate the provider and patient knowledge as well as adherence to screening guidelines would be needed to highlight reasons for this gap in care.

A Cross-Sectional Study of the Prevalence of Anal Dysplasia among Women with High-Grade Cervical, Vaginal, and Vulvar Dysplasia or Cancer: The PANDA Study.

High-risk human papillomavirus (HR-HPV) infection is a risk factor for anal cancer, yet no anal cancer screening guidelines exist for women with lower genital tract HPV-related disease. We sought to describe the prevalence of anal HR-HPV or cytologic abnormalities in such women. This cross-sectional study was performed between October 2018 and December 2021. Inclusion criteria were ≥21 years of age and a prior diagnosis of high-grade dysplasia/cancer of the cervix, vagina, or vulva. Participants underwent anal cytology and anal/cervicovaginal HR-HPV testing. Women with abnormal anal cytology were referred for high-resolution anoscopy (HRA). 324 evaluable women were enrolled. Primary diagnosis was high-grade dysplasia/cancer of the cervix (77%), vagina (9%), and vulva (14%). Anal HR-HPV was detected in 92 patients (28%) and included HPV-16 in 24 (26%), HPV-18 in 6 (7%), and other HR-HPV types in 72 (78%) patients. Anal cytology was abnormal in 70 patients (23%) and included atypical squamous cells of undetermined significance (80%), low-grade squamous intraepithelial lesion (9%), high-grade intraepithelial lesion (HSIL; 1%), and atypical squamous cells-cannot rule out HSIL (10%). Of these patients, 55 (79%) underwent HRA. Anal biopsies were performed in 14 patients: 2 patients had anal intraepithelial neoplasia (AIN) 2/3, 1 patient had AIN 1, and 11 patients had negative biopsies. Both patients with AIN 2/3 had a history of cervical dysplasia. Our results suggest an elevated risk of anal HR-HPV infection and cytologic abnormalities in women with lower genital tract dysplasia/cancer. These results add to the growing body of evidence suggesting the need for evaluation of screening methods for anal dysplasia/cancer in this patient population to inform evidence-based screening recommendations.

Can Adjuvant HPV Vaccination Be Helpful in the Prevention of Persistent/Recurrent Cervical Dysplasia after Surgical Treatment?-A Literature Review.

Simple SummaryPrimary prophylactic, early detection and the treatment of precancerous lesions are the main goals of cervical cancer screening. Despite effective surgical treatment methods, using loop electrosurgical excision procedures and conization, the overall risk of the recurrence of HSIL lesions remains at approximately 6.6%. There is increasing evidence of the potential role of HPV vaccines in the adjuvant setting and their impact on the reduction of disease recurrence. This review aims to analyze the up-to-date research concerning the use and efficacy of secondary human papilloma virus (HPV) vaccination as an adjuvant method to surgical treatment in patients diagnosed with cervical HSILs.Cervical cancer formation is preceded by precursor lesions, including low-grade squamous intraepithelial lesions (LSILs) and high-grade squamous intraepithelial lesions (HSILs), which are usually diagnosed in women of reproductive age. Despite the recent advanced diagnostic and treatment methods, including colposcopy, the loop electrosurgical excision procedure (LEEP), and surgical conization, the recurrence or residual disease affects as many as 6.6% of patients. The lesions are often associated with human papilloma virus (HPV) infection. As HPV persistence is the leading and only modifiable factor affecting the risk of progression of CIN lesions into high-grade cervical dysplasia and cancer, it has been proposed to conduct adjuvant vaccination in patients treated for high-grade cervical dysplasia. To date, no vaccine has been approved for therapeutic use in patients diagnosed with HSILs; however, attempts have been made to determine the use of HPV prophylactic vaccination to reduce recurrent HSILs and prevent cervical cancer. The aim of this review was to analyze the up-to-date literature concerning the possible use of secondary human papilloma virus (HPV) vaccination as an adjuvant method to surgical treatment in patients diagnosed with cervical HSILs. Adjuvant HPV vaccination after surgical treatment may reduce the risk of recurrent cervical dysplasia.

Characterizing the vaginal microbiome in patients with high grade cervical dysplasia (277)

Objectives: The influence of the vaginal microbiome on risk for cervical dysplasia and cancer is unknown. It is hypothesized that the microbiome can impact the infectivity of human papillomavirus, and some bacteria may even have pro-oncogenic effects. The impact of dysplasia and cancer treatment on the microbiome is also unknown. The objective of this study was to characterize the vaginal microbiome of patients with high-grade cervical dysplasia and determine whether microbiome phylotypes changed after the cervical loop electrosurgical excision procedure (LEEP). Methods: Pre-menopausal women undergoing LEEP for high-grade cervical dysplasia were recruited. Vaginal swabs were collected prior to the LEEP procedure and six weeks post-procedure. DNA was extracted, and the hypervariable V4 region of the bacterial and archaeal 16S rRNA gene was amplified and sequenced using Illumina next-generation sequencing. Sequenced reads were processed and quality-filtered using AdapterRemoval and clustered into operational taxonomic units (OTUs) using a closed-reference OTU-picking strategy implemented in QIIME. A 97% identity threshold was used, and taxonomy was assigned using the EZTaxon database. The resulting OTU table was rarefied to 10,000 sequences. Conclusions: Our findings are consistent with existing data demonstrating an association between an L. iners-dominant microbiome and severe cervical dysplasia. Additionally, a more diverse and less Lactobacillus-dominated vaginal microbiome has been shown to be more prevalent amongst HPV-positive women. In contrast to published data, our findings, while based on a small number of cases, did not demonstrate consistent alterations in vaginal microbiota after the LEEP procedure. We plan to collect more longitudinal data on the persistence and progression of dysplasia in association with vaginal microbiomes to better understand the relationship between these two entities. Objectives: The influence of the vaginal microbiome on risk for cervical dysplasia and cancer is unknown. It is hypothesized that the microbiome can impact the infectivity of human papillomavirus, and some bacteria may even have pro-oncogenic effects. The impact of dysplasia and cancer treatment on the microbiome is also unknown. The objective of this study was to characterize the vaginal microbiome of patients with high-grade cervical dysplasia and determine whether microbiome phylotypes changed after the cervical loop electrosurgical excision procedure (LEEP). Methods: Pre-menopausal women undergoing LEEP for high-grade cervical dysplasia were recruited. Vaginal swabs were collected prior to the LEEP procedure and six weeks post-procedure. DNA was extracted, and the hypervariable V4 region of the bacterial and archaeal 16S rRNA gene was amplified and sequenced using Illumina next-generation sequencing. Sequenced reads were processed and quality-filtered using AdapterRemoval and clustered into operational taxonomic units (OTUs) using a closed-reference OTU-picking strategy implemented in QIIME. A 97% identity threshold was used, and taxonomy was assigned using the EZTaxon database. The resulting OTU table was rarefied to 10,000 sequences. Conclusions: Our findings are consistent with existing data demonstrating an association between an L. iners-dominant microbiome and severe cervical dysplasia. Additionally, a more diverse and less Lactobacillus-dominated vaginal microbiome has been shown to be more prevalent amongst HPV-positive women. In contrast to published data, our findings, while based on a small number of cases, did not demonstrate consistent alterations in vaginal microbiota after the LEEP procedure. We plan to collect more longitudinal data on the persistence and progression of dysplasia in association with vaginal microbiomes to better understand the relationship between these two entities.

PANDA: A prospective study of the prevalence of anal dysplasia among women with high-grade cervical, vaginal, and vulvar dysplasia or cancer (107)

<b>Objectives:</b> Infection with high-risk human papillomavirus (HR HPV) is a risk factor for anal cancer, yet no evidence-based anal cancer screening guidelines exist for women with lower genital tract HPV-related dysplasia and/or cancer. We sought to describe the prevalence of anal dysplasia in women with cervical, vaginal, and vulvar dysplasia or cancer. <b>Methods:</b> This cross-sectional study was performed at a tertiary cancer center and its partner public safety-net hospital. Inclusion criteria were ≥21 years of age and a diagnosis of high-grade dysplasia or cancer of the cervix, vagina, or vulva. Women with a history of anal dysplasia or cancer were excluded. Participants underwent anal cytology, as well as anal and cervical HR HPV testing. Participants also underwent cervical cytology and/or colposcopy indicated as part of their standard of care management. Women with abnormal anal cytology were referred for high-resolution anoscopy (HRA). <b>Results:</b> A total of 275 evaluable women were prospectively enrolled between October 2018 and June 2021. The median age was 45 years (range: 21-78). Primary diagnosis was high-grade dysplasia/cancer of the cervix (<i>n</i>=209, 76.0%), vagina (<i>n</i>=25, 9.1%), and vulva (<i>n</i>=41, 14.9%). Five participants (2.0%) were HIV positive. Anal cytology was abnormal in 62 patients (23.8%) and included HSIL (<i>n</i>=1, 1.6%), ASC-H (<i>n</i>=7, 11.3%), ASCUS (<i>n</i>=48,77.4%), and LSIL (<i>n</i>=6, 9.7%). HR anal HPV was detected in 81 patients (32.3%), and included HPV16 in 15 (18.5%), HPV18 in three (3.7%), and other HR HPV types in 63 (77.8%) patients. Nine patients (11.1%) had more than one type of HR anal HPV. HR cervical HPV was detected in 129 patients (47.1%) and included HPV16 in 37 (28.7%), HPV18 in five (3.9%), and other high-risk HPV types in 87 (67.4%) patients. Twelve patients (9.3%) had more than one type of HR cervical HPV. Of those who tested positive for HR HPV, 55 patients (38.5%) had both anal and cervical HR HPV detected. In contrast, 26 (18.2%) had positive anal but negative cervical HR HPV, and 62 (43.4%) had negative anal but positive cervical HR HPV. Anal samples were insufficient for cytology in seven patients (2.6%) and HR HPV testing in 21 patients (7.7%). Of the 62 patients with abnormal anal cytology, 44 (71.0%) underwent HRA. Anal biopsies were performed in 12 patients and showed high-grade anal dysplasia in two patients and were negative in ten patients. Both patients with high-grade anal dysplasia had a primary diagnosis of high-grade cervical dysplasia. There was no association between abnormal anal cytology or positive anal HR HPV testing and the primary site of disease (cervix, vagina, or vulva). There were no cases of anal cancer diagnosed. <b>Conclusions:</b> Our results suggest a high prevalence of anal HR HPV infection and cytologic abnormalities in women with lower genital tract dysplasia or cancer. Further study is needed to determine the rate of progression to high-grade anal dysplasia and cancer to inform appropriate screening guidelines in this population.

A pilot study of a collaborative screening program for HPV-related dysplasia and malignancy in gynecologic oncology patients (376)

<b>Objectives:</b> Human papillomavirus (HPV)-related dysplasia or malignancy is associated with a significantly increased risk of second site dysplasia or malignancy. However, screening for additional potential sites of HPV-related pathology is not routinely performed. The primary objective of this study was to determine the feasibility and acceptability of concurrent anal, cervical, or vulvovaginal screening in patients with a history of HPV-related gynecologic high-grade dysplasia or malignancy. The secondary objective was to assess patient knowledge regarding HPV screening and risks. <b>Methods:</b> Women with a diagnosis of cervical high-grade dysplasia or cancer and vulvovaginal high-grade dysplasia or cancer were enrolled during a one-year pilot period. Clinical data on all enrolled subjects were obtained using electronic medical records. All enrolled subjects completed a baseline HPV-knowledge survey. Subjects with cervical dysplasia or malignancy underwent vulvar examination with acetic acid and anoscopy. Subjects with vulvovaginal dysplasia or malignancy underwent a Pap test if indicated and anoscopy. Gynecologic oncologists were trained in anoscopy by colorectal surgery colleagues. Appropriate referrals were made for abnormal findings on screening exams. Feasibility was assessed by compliance using study acceptance rate, screening procedure adherence, and referral adherence. Acceptability was assessed using an acceptability Likert scale completed by subjects after screening procedures were performed. Descriptive statistics were used to assess the data. <b>Results:</b> A total of 103 women with a diagnosis of high-grade vulvovaginal or cervical dysplasia or carcinoma were approached regarding study enrollment; of these, 74 (71.8%) enrolled. Thirty-three (44.5%) had a primary diagnosis of cervical dysplasia or malignancy, and 43 (58.1%) had a primary diagnosis of vulvovaginal dysplasia or malignancy. About 50/74 (68%) were White, and 17/74 (23%) were Black. The median score on the HPV knowledge assessment was 8.1 ± 1.6 (max score of 10). Fifty-two patients (69%) reported that their provider discussed a possible diagnosis of HPV with them; 56 patients (75%) believed that HPV caused ovarian cancer. All enrolled subjects completed screening procedures, and 73/74 (98.6%) patients rated the procedure as acceptable (score of 5/5). On exam, 14 (18.9%) subjects had abnormalities noted; seven (9.5%) were referred for colorectal surgical evaluation, and 6/7 (85.7%) were compliant with their referral appointments. <b>Conclusions:</b> Screening exams for other HPV-related dysplasias and malignancies, including Pap tests, vulvovaginal inspection, and anos- copy, can be performed by gynecologic oncologists and are acceptable to patients with abnormal findings in almost one in five women. Improvements in communication and patient education regarding HPV should be the focus of future research efforts.

Effectiveness, immunogenicity, and safety of the quadrivalent HPV vaccine in women and men aged 27–45 years

ABSTRACT Among women aged 27–45 years, the quadrivalent human papillomavirus (qHPV; HPV6/11/16/18) vaccine was generally well tolerated, efficacious, and immunogenic in the placebo-controlled FUTURE III study (NCT00090220; n = 3253). The qHPV vaccine was also generally well tolerated and highly immunogenic in men aged 27–45 years who participated in the single-cohort mid-adult male (MAM) study (NCT01432574; n = 150). Here, we report results of a long-term follow up (LTFU) extension of FUTURE III with up to 10 years follow-up. To understand the relevance of the mid-adult women LTFU study in the context of mid-adult men vaccination, we report results from post-hoc, cross-study immunogenicity analyses conducted to compare immunogenicity (geometric mean titers; GMTs) at 1-month post-qHPV vaccine dose 3 in women and men aged 27–45 years versus women and men aged 16–26 years from prior efficacy studies. The qHPV vaccine demonstrated durable protection against the combined endpoint of HPV6/11/16/18-related high-grade cervical dysplasia and genital warts up to 10 years (median 8.9) post-dose 3 and sustained HPV6/11/16/18 antibody responses through approximately 10 years in women aged 27–45 years. Efficacy of qHPV vaccine in men aged 27–45 years was inferred based on the cross-study analysis of qHPV vaccine immunogenicity demonstrating non-inferior HPV6/11/16/18 antibody responses in men aged 27–45 years versus 16–26 years. In conclusion, durable effectiveness of the qHPV vaccine was demonstrated in women 27–45 years of age, and vaccine efficacy was inferred in men 27–45 years of age based on the serological results.

An investigation into human papillomavirus (HPV) vaccination for patients undergoing surgery for high-grade cervical or vulvar dysplasia

IntroductionEligibility for the human papillomavirus (HPV) vaccine now includes adults 27 through 45 years. It has not been reported how providers are addressing HPV vaccination in patients with existing preinvasive disease. Our objectives were to determine the rates at which vaccination is offered to and received by patients undergoing surgery for high-grade cervical or vulvar dysplasia. Materials and MethodsThis was a single-institution retrospective cohort study including patients ages 18 through 45 years undergoing surgery for high-grade cervical or vulvar dysplasia from 10/2018 to 2/2020. Our primary outcome was the rate at which HPV vaccination was discussed at the pre- and/or post-operative visits. The secondary outcome was the rate of vaccine uptake in these individuals. Characteristics of those offered HPV vaccination were compared to those not offered vaccination. ResultsOf the 115 patients included, 36 (31.3%) had HPV vaccination addressed in the perioperative setting. Thirty-two of these patients had never been vaccinated, and 21 of these (65.6%) went on to receive partial or complete HPV vaccination. Those in whom HPV vaccination was addressed were more likely to be under 27 years (RR 3.2; 95% CI 2.1–4.8) and less likely to be smokers (RR 0.5; 95% CI 0.2–0.9) or have prior excisional procedures (RR 0.3; 95% CI 0.1–0.9). The absolute rate of discussing HPV vaccination with patients improved from 26.0% within six months of vaccine age eligibility expansion, to 35.4% after six months (P = 0.32). ConclusionsProviders did not consistently address HPV vaccination among patients being treated for high-grade cervical or vulvar dysplasia despite the potential benefits. However, a high proportion of these patients are amenable to vaccination. Quality improvement initiatives are warranted to increase the rate of HPV vaccine counseling in this context.