Positive High-risk Human Papillomavirus Research Articles

Evaluation of the relationship between Doppler predictors with human papillomavirus types, smear and cervical biopsy results

Objectives: The study aims to investigate whether there is any difference between human papillomavirus (HPV) types, smear results, and colposcopic biopsy results in terms of iliac, uterine, and cervical artery pulsatility and resistive index values in high-risk HPV positive patients.Methods: Iliac, uterine, and cervical artery pulsatility and resistive index values were determined by pelvic Doppler ultrasonography in patients who applied for high-risk HPV positivity and underwent colposcopyguided cervical biopsy. Results: There was no difference between HPV types and Pap-smear results and the pulsatility and resistive indices of the iliac artery, uterine artery, and cervical artery. It was observed that the mean cervical artery pulsatility index of the patients whose colposcopic cervical biopsy result was cervical intraepithelial neoplasia (CIN) 1 was 1.61 ± 0.43 and the cervical artery pulsatility index of the patients with CIN 2-3 was 1.15 ± 0.28, and a statistically significant difference was found between them (p = 0.038). There was no difference between other Doppler indices and colposcopic cervical biopsy results. Conclusions: Doppler indices such as cervical artery pulsatility index may be helpful in the evaluation of cervical cancer precursor lesions.

Human Papillomavirus genotypes associated with cervical intraepithelial lesions among Saudi women.

HPV is responsible for over 90% of cervical cancer worldwide. HPV has numerous subtypes with great variety distribution in different geographical regions. Thus, the present study aimed at assessing Human Papillomavirus (HPV) genotypes associated with cervical intraepithelial lesions among Saudi women. The current study collected cervical smears from 300 women transferred to a cytopathology laboratory between May 2020 and May 2021. The studied women were referred to do Pap smear because of gynecologic complaints. Positive HPV testing was established in 4.7%. Most positive cases were identified in the age range of 14-50 years, followed by 51-60 years, representing 50% and 35.7%, respectively. The risk of HPV infection was significantly high in the age between 40-50 years, the odds ratio (OR), 95% confidence interval (95% CI), OR (95% CI) = 3.0137 (1.0228 to 8.8797), p = 0.0454, z statistic = 2.001. About 57% of the cases of HPV were found with cytological atypia. The risk of HPV in inducing cytological atypia, the OR (95%CI) = 1.8546 (2.9386 to 27.0952), p = 0.0001, z statistic = 3.862. Inflammatory cells infiltrate was identified in 43% of HPV-positive cases. The risk of HPV in inducing inflammatory changes, the OR (95% CI) = 2.6423 (0.8850 to 7.8887), p = 0.0817, z statistic = 1.741. The prevalence of High-risk human papillomavirus is relatively low in the AL-Madinah area, Saudi Arabia. Cervical cytological atypia corresponds to the positive HR-HPV findings. HR-HPV infection or cervical cytological atypical changes induce inflammatory cell infiltrates. HR-HPV infection is more common among elderly Saudi women.

Risk factors predicting residual lesion in subsequent hysterectomy following cold knife conization (CKC) for high-grade squamous intraepithelial lesion (HSIL)

ObjectiveTo determine risk factors predicting residual lesion in a subsequent hysterectomy follow a cold knife conization (CKC) for high-grade squamous intraepithelial lesion (HSIL).MethodBetween January 2010 and December 2021, a total of 740 patients who underwent a hysterectomy within 3 months after CKC for HSIL were included in this study. We analyzed their demographic features and pathological parameters. A logistic regression model was used to analyze the relationship between parameters and residual lesion in subsequent hysterectomy specimens.Results104 (14.1%) had residual lesion in the hysterectomy specimen, 3 patients with microinvasive carcinoma. The rate of residual lesion in patients with positive endocervical margin was 31.3%, with positive ectocervical margin was 15.3%, with positive combine margin was 38.6%. In multivariate analysis, positive margin (OR 4.015; 95% CI 2.526–6.381; P < 0.001), glandular involvement (OR 3.484; 95% CI 1.457–8.330; P = 0.005), HPV16/18 infection (OR 2.804; 95% CI 1.705–4.611; P < 0.001) and multiple HR-HPV infection (OR 1.813; 95% CI 1.130–2.909; P < 0.014) were independent risk factors for residual lesion. The AUC calculated by logistic regression model was 0.78.ConclusionPositive margin, positive glandular involvement, HPV16/18 and multiple HR-HPV infection were independent high risk factors of residual lesion in a subsequent hysterectomy following CKC for HSIL.

Predictors of treatment failure for adenocarcinoma in situ of the uterine cervix: Up to 14 years of recorded follow-up.

The incidence of adenocarcinoma-in-situ (AIS) of the uterine cervix is rising, with invasive adenocarcinoma becoming increasingly common relative to squamous cell carcinoma. The present study reviewed a cohort of 84 patients first-time treated by conization for histologically-confirmed AIS from January 2001 to January 2017, to identify risk factors associated with recurrent/persistent AIS as well as progression to invasive cervical cancer. Nearly 80% of the patients were age 40 or younger at conization. Endocervical and ectocervical margins were deemed clear in 42 of the patients. All but two patients had ≥1 follow-up, with post-conization high-risk human papilloma virus (HPV) results documented in 52 patients. Altogether, 12 histopathologically-confirmed recurrences (14.3%) were detected; two of these patients had microinvasive or invasive carcinoma. In three other patients cytology showed AIS, but without recorded histopathology. Eight patients underwent hysterectomy for incomplete resection very soon after primary conization; they were not included in bivariate or multivariate analyses. Having ≥1 post-follow-up positive HPV finding yielded the highest sensitivity for histologically-confirmed recurrence: 87.5 [95% confidence interval (CI) 47.4-99.7]. Current or historical smoking status provided highest specificity: 94.4 (95% CI 72.7-99.9) and overall accuracy: 88.0 (95% CI 68.8-97.5) for histologically-confirmed recurrence. With multiple logistic regression (MLR), adjusting for age at conization and abnormal follow-up cytology, positive HPV18 was the strongest predictor of histologically-confirmed recurrence (P<0.005). Having ≥2 positive HPV results also predicted recurrence (P<0.02). Any unclear margin yielded an odds ratio 7.21 (95% CI 1.34-38.7) for histologically-confirmed recurrence adjusting for age, but became non-significant when including abnormal cytology in the MLR model. The strong predictive value of HPV, particularly HPV18 and persistent HPV positivity vis-à-vis detected recurrence indicated that regular HPV testing for patients treated for AIS is imperative. In conclusion, furthering a participatory approach, including attention to smoking with encouragement to attend needed long-term follow-up, can better protect these patients at high risk for cervical cancer.

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.

Integrating cervical cancer screening and prevention treatment with voluntary family planning in Mozambique (038)

<b>Objectives:</b> Mozambique has cervical cancer incidence and mortality rates of 50.2 and 38.7 per 100,000 women, respectively. These high rates are due in part to a lack of access to cervical cancer screening and few medical providers skilled in the treatment of women with preinvasive cervical disease. The objective of this study was to develop, implement and test models integrating cervical cancer screening and prevention treatment with voluntary family planning programs using strategies to optimize the uptake and health impact of both services. <b>Methods:</b> Women aged 30 to 49 in Maputo City and Gaza Province, Mozambique, were prospectively enrolled in the study. Women were offered cervical cancer screening and/or voluntary family planning services as appropriate. Women were screened for high-risk human papillomavirus (HPV) DNA using the GeneXpert® (Cepheid Inc, Sunnyvale, CA, USA) platform. Participants were offered self-collection or provider collection of cervicovaginal samples. HPV-positive women underwent a pelvic examination by a nurse and visual assessment for treatment using visual inspection with acetic acid to determine eligibility for ablation. Prior to treatment, a photograph of the cervix was taken for quality assurance. Patients with lesions eligible for ablation underwent thermal ablation (87%) or cryotherapy (13%). If ineligible, women were referred to a gynecologist for evaluation and excisional treatment as appropriate. Local nurses and doctors were trained in cervical cancer screening and treatment of pre-invasive disease. Continuing education sessions were held weekly. Surveys were conducted to evaluate the integration of cervical cancer screening and family planning services, and these results will be reported separately. <b>Results:</b> From January 2020 to July 2021, 4,344 women were enrolled and screened with HPV testing. The median age of participants was 38 years. Among the participants, 45.7% of women were living with HIV (WLWH). The HPV positivity rate was 34.0% overall and 43.6% in WLWH. A total of 96% of the patients chose self-collection of HPV testing. Of the 1,477 HPV-positive women, 87.8% had been evaluated and treated. Treatments included ablation (<i>n</i>=1193, 80.8%), LEEP (<i>n</i>=84, 5.7%) or cold-knife-conization (<i>n</i>=4, 0.3%). Fifteen (1.0%) women were diagnosed with invasive cancer and navigated to gynecologic oncology treatment, whereas 12.2% were lost to follow-up. <b>Conclusions:</b> Preliminarily results indicate it is feasible to screen women for cervical cancer with primary HPV testing using self-collected samples in Mozambique. Almost 90% of screen-positive patients completed follow-up treatment. This study is ongoing, supporting a comprehensive approach to improve screening methods and uptake through integration with voluntary family planning, to test the feasibility of HPV testing and self-collection, and to improve provider education and skills through regular training.

Cytology and High-Risk Human Papillomavirus Test for Cervical Cancer Screening Assessment.

Background: A new nationwide screening strategy was implemented in Germany in January 2020. No data are available for women referred to certified dysplasia units for secondary clarification after primary diagnosis by a local physician. We therefore investigated combined testing with Papanicolaou smears and high-risk human papillomavirus (hrHPV) and compared the data with the final histological findings. Methods: Between January 2015 and October 2020, all referred women who underwent colposcopy of the uterine cervix in our certified dysplasia unit were included. Cytology findings were classified using the Munich III nomenclature. Results: A total of 3588 colposcopies were performed in 3118 women, along with Pap smear and hrHPV co-testing, followed by histology. Women with Pap II-p (ASC-US) and a positive hrHPV co-test had a 22.4% risk for cervical intraepithelial neoplasia (CIN) 3/high-grade squamous intraepithelial lesion (HSIL). The risk of CIN 3/HSIL was 83.8% in women with Pap IVa-p (HSIL) and a positive hrHPV co-test. A positive hrHPV co-test increased the risk for HSIL+ (OR 5.942; 95% CI, 4.617 to 7.649; p < 0.001) as compared to a negative hrHPV co-test. Conclusions: The accuracy of Pap smears is comparable with the screening results. A positive hrHPV test increases the risk for HSIL+ fivefold. Colposcopy is necessary to diagnose HSIL+ correctly.

Colposcopy non-attendance following an abnormal cervical cancer screening result: a prospective population-based cohort study

BackgroundA considerable proportion of cervical cancer diagnoses in high-income countries are due to lack of timely follow-up of an abnormal screening result. We estimated colposcopy non-attendance, examined the potential factors associated and described non-attendance reasons in a population-based screening study.MethodsData from the MARZY prospective cohort study were analysed. Co-test screen-positive women (atypical squamous cells of undetermined significance or worse [ASC-US+] or high-risk human papillomavirus [hrHPV] positive) aged 30 to 65 years were referred to colposcopy within two screening rounds (3-year interval). Women were surveyed for sociodemographic, HPV-related and other data, and interviewed for non-attendance reasons. Logistic regression was used to examine potential associations with colposcopy attendance.ResultsAt baseline, 2,627 women were screened (screen-positive = 8.7%), and 2,093 again at follow-up (screen-positive = 5.1%; median 2.7 years later). All screen-positives were referred to colposcopy, however 28.9% did not attend despite active recall. Among co-test positives (ASC-US+ and hrHPV) and only hrHPV positives, 19.6% were non-attendees. Half of only ASC-US+ screenees attended colposcopy. Middle age (adjusted odds ratio [aOR] = 1.55, 95% CI 1.02, 4.96) and hrHPV positive result (aOR = 3.04, 95% CI 1.49, 7.22) were associated with attendance. Non-attendance was associated with having ≥ 3 children (aOR = 0.32, 95% CI 0.10, 0.86). Major reasons for non-attendance were lack of time, barriers such as travel time, need for childcare arrangements and the advice against colposcopy given by the gynaecologist who conducted screening.ConclusionsFollow-up rates of abnormal screening results needs improvement. A systematic recall system integrating enhanced communication and addressing follow-up barriers may improve screening effectiveness.

Cyberchondria levels in women with human papilloma virus.

To investigate the level of cyberchondria in patients with high-risk human papilloma virus (HPV) positivity. One hundred and forty women who applied to our clinic between July 2020 and September 2020 and were diagnosed with high-risk HPV positivity or abnormal uterine bleeding (AUB) were included in the study. The Cyberchondria Severity Scale (CSS) was administered face-to-face to the participants. CSS and subscales scores of both groups of patients were evaluated and compared. The mean score of the patients on the CSS was 78.54 ± 22.09 and the patients with AUB and HPV(+) was 67.43 ± 19.87 and 84.16 ± 21.08, respectively. The mean subscale scores were as follows, compulsion 13.89 ± 6.49, distress 20.07 ± 7.54, excessiveness 22.40 ± 8.18, reassurance 15.07 ± 6.56, and mistrust of medical professionals 7.26 ± 3.62. The mean scores of the CSS and subscales except for the mistrust of medical professional subscale were higher in patients who were HPV-positive than in other patients. Women with HPV have higher levels of cyberchondria. Medical professionals can reduce this anxiety by giving information to patients.

Role of Immunity and Vaginal Microbiome in Clearance and Persistence of Human Papillomavirus Infection.

Cervical cancer disproportionately affects women of reproductive age, with 80% of cases occurring in low- and middle-income countries. Persistent infection with high-risk human papillomavirus (HPV) genotypes has been described as the most common non-systemic biological risk factor for the development of cervical cancer. The mucosal immune system plays a significant role in controlling HPV infection by acting as the first line of host defense at the mucosal surface. However, the virus can evade host immunity using various mechanisms, including inhibition of the antiviral immune response necessary for HPV clearance. Pro-inflammatory cytokines and the vaginal microbiome coordinate cell-mediated immune responses and play a pivotal role in modulating immunity. Recently, diverse vaginal microbiome (associated with bacterial vaginosis) and genital inflammation have emerged as potential drivers of high-risk HPV positivity and disease severity in women. The potential role of these risk factors on HPV recurrence and persistence remains unclear. This article reviews the role of cellular or cytokine response and vaginal microbiome dysbiosis in the clearance, persistence, and recurrence of HPV infection.

Human Papillomavirüs (HPV), Servikal Smear ve Kolposkopik Biyopsi Sonuçlarının Karşılaştırılması: Serviks Kanseri Taramasında Bir Üniversite Hastanesinin 4 Yıllık Deneyimi

Aim: Cervical cancer screening guidelines gradually recommend human papillomavirus (HPV) DNA testing since sensitivity of cytology is relatively low. This study aimed to evaluate correlation between HPV, cervical smear cytology and colposcopy directed biopsy results.&#x0D; Material and Methods: Patients who underwent colposcopy directed biopsy in Ordu University Training and Teaching Hospital between January 2018 and December 2021 were retrospectively reviewed. Patients with any high-risk HPV positivity who had cervical smear cytology and colposcopy directed biopsy results were included to this study. Results of HPV subtypes, cervical smear and histologic biopsy were recorded.&#x0D; Results: A total of 734 patients were included to this study. The mean age of the patients was 41.9 ± 7.36 years. Hundred and sixty-five (22.5%) patients had HPV 16 alone, 35 (4.8%) had HPV 18 alone, 354 (48.2%) had other high-risk HPV subtypes alone and 180 (24.5%) had more than one high-risk HPV subtypes. Two hundred and ninety-eight (40.6%) had HPV 16 or HPV 18 either alone or in combination with other subtypes. Majority of the patients (55.3%) had normal cervical smear results followed by ASC-US (27%). Colposcopy directed biopsy results were as follows: 452 (61.6%) normal, 199 (27.1%) CIN 1, 36 (4.9%) CIN 2, 42 (5.7%) CIN 3 and 5 (0.7%) squamous cell cancer. 66.1% of the patients with HPV 16 and/or HPV 18 had normal cervical cytology results, but they had significantly more ≥CIN 2 lesions compared to other high-risk HPV subtypes (19.8% vs 5.5%, p

Feasibility of self-sampling and human papillomavirus testing in rural and urban areas for cervical cancer prevention in Bolivia: an observational study

Cervical cancer is a major health problem in Latin America. In 2019, the Italian Agency for Development Cooperation (La Paz regional site) conducted a pilot study to estimate the prevalence of high-risk human papillomavirus (HPV) and the feasibility of HPV screening in Bolivia through self-sampling and portable and transportable laboratory instruments for HPV testing in urban and rural areas. Women aged 20-65 years from La Paz (urban area), Torotoro (rural area), and Acasio (rural area) were enrolled by invitation from local public health centres between Dec 1, 2019, and June 30, 2021. Self-sampling was carried out with the Viba-Brush system (Rovers, Oss, Netherlands) and samples were preserved in ThinPrep containers (Hologic Corporation, San Diego, CA, USA). The GeneXpert system (Cepheid, Sunnyvale, CA, USA) for high-risk HPV testing detects HPV E6 and E7 DNA via real-time PCR in a mobile system of easy execution requiring minimal manual intervention. The system provides results in about 1 h. Women with a positive test for HPV types 16, 18, or 45 were invited for a follow-up colposcopy. Data analysis was done considering the following age groups: <20, 20-34, 35-44, and 45-65 years. The study terminated later than expected (in June, 2021, instead of in November, 2020) due to the COVID-19 pandemic, and follow-up test retrieval is still ongoing. 2201 women were enrolled: 622 (28·3%) in La Paz, 768 (34·9%) in Torotoro, and 811 (36·8%) in Acasio. Only one sample was collected from each participant. 2076 (94·3%) of 2201 samples were adequate (yielding a negative or positive result) for HPV testing. 264 (12·7%) samples were positive for high-risk HPV. The observed prevalence was higher in the 20-34 age group (145 [15·5%] of 938) than in the 35-44 age group (60 [10·5%] of 571) and in the 45-65 years age group (37 [8·3%] of 444). Ages were not recorded for 123 samples, which are not included in the prevalence-per-age analysis. HPV positivity was detected in 94 (15·3%) of 614 samples from women from La Paz, 86 (12·9%) of 667 samples from patients from Torotoro, and 84 (10·6%) of 795 samples from patients from Acasio (risk ratio urban vs rural 1·4 [95% CI 1·04-1·80], p=0·029). Overall positivity was 58 (7·3%) of 795 for HPV type 16 and 38 (1·8%) of 2076 for HPV types 18 and 45. From the follow-up data available to date, all high-grade lesions detected on follow-up colposcopy were related to HPV types 16, 18, or 45, isolated or in co-infection with other high-risk HPV types. The total and age-adjusted prevalence of high-risk HPV infection in rural and urban areas in Bolivia, as measured with a validated test for screening, is similar to that observed in Europe and the USA. Our study shows that a screening protocol for HPV testing with self-sampling would be feasible in urban and rural areas in Bolivia, and that the high prevalence of cervical cancer in Bolivia is likely to be related to the scarcity of screening programmes, and not to a higher occurrence of high-risk HPV infections. Carrying out HPV tests locally avoids the issues associated with transport and storage of the material collected, and allows the participant to wait in the clinic for the test result. However, the cost of HPV testing, at about €15 per test, is still a major hurdle for low-income countries. Joint initiatives between the national scientific community, international institutions, and manufacturers could allow widespread testing of HPV to be rolled out in Bolivia and other countries with similar contexts. Italian Agency for Development Cooperation (Italian Ministry of Foreign Affairs), as a part of an ongoing technical assistance programme with the Bolivian Ministry of Health.

Serum vitamin D levels in high-risk HPV infected patients, is there any relation?

Objective: Human Papilloma Virus (HPV) is a sexually transmittable virus and is the main etiologic cause of uterine cervical cancers. Beyond that, vitamin D is a steroid structured lipid-soluble vitamin, enhancing both humoral and cellular immune responses. In our study, we aimed to investigate the relationship between vitamin D levels and high-risk HPV infections. Material and methods: A total of 143 patients who applied to the gynecology outpatient clinic between June 2020 and August 2020 were included in the study. Patients with high-risk HPV positivity constituted the study group, and HPV-negative patients constituted the control group. Serum vitamin D levels were compared between the groups. Results: The mean vitamin D level of all patients included in the study, HPV(+) and HPV(-) patients were 17.57±8.73, 17.54±9.20 and 17.63±7.83, respectively. In the study group 10.2% of the patients and in the control group 8.5% had adequate vitamin D levels. No significant differences in vitamin D levels and in terms of distribution according to categorical vitamin D level have been observed between the groups (p=0.774, p=0.989). Conclusion: Vitamin D levels were comparable between HPV positive and HPV negative groups, but study and controls both had very low sufficient vitamin D levels. In Turkey and especially in our region (Zonguldak), vitamin D deficiency is almost endemic, and this might be the main reason that both of the groups have very similar vitamin D measurements.

Abstract 2230: Extended human papillomavirus genotyping to predict progression to high-grade cervical precancer: A prospective cohort study in the southeastern United States

Abstract Background: High-risk human papillomavirus (hrHPV) testing is recommended for primary cervical cancer screening and is used alongside cytology to triage screening abnormalities to colposcopy. Most screening-based hrHPV tests involve pooled detection of any hrHPV type or of HPV 16/18 only. Extended HPV genotyping, particularly of non-16/18 hrHPV types, may improve risk stratification for millions of cervical abnormalities detected each year, but HPV genotype-specific progression risks are not well characterized. HPV genotype-specific incidence of high-grade cervical intraepithelial neoplasia or more severe (CIN2+) was examined among individuals with normal or low-grade (CIN1) histology following an abnormal screening cytology result. Methods: A US-based prospective, multiracial cohort of 343 colposcopy referral patients with normal (n=226) or CIN1 (n=117) histology was assessed. Baseline cervical samples underwent HPV DNA genotyping. Participants were followed for up to five years. Genotype-specific CIN2+ incidence rates (IR) were estimated with accelerated failure time models for interval-censored data. Cumulative CIN2+ risk over five years was estimated non-parametrically and compared for HPV risk groups (HPV 16/31/18, else HPV 33/58/52/45, else HPV 39/68/35/51/59/56/66) and age groups (ages 21-24, 25-29, 30+). Results: At enrollment, median participant age was 30.1 years; 67.1% were hrHPV-positive. During follow-up (median 24.3 months), 24 participants progressed to CIN2+ (7.0%; 6.2% among normal histology and 8.6% among CIN1). CIN2+ IR among hrHPV-positive participants was 3.2/1,000 person-months. CIN2+ IRs were highest for HPV 16 (IR 8.3; 95% CI 4.1, 16.6), HPV 33 (IR 7.8; 95% CI 2.0, 31.3), and HPV 58 (IR 4.9; 95% CI 1.2, 19.6). IRs were highest for HPV 16, 68, and 33 among normal histology and for HPV 33, 31, 16, and 58 among CIN1. Five-year CIN2+ risks were 0.27 for HPV 16/31/18, 0.11 for HPV 33/58/52/45, and 0.13 for HPV 39/68/35/51/59/56/66 (p=0.04). CIN2+ risk did not differ by age group. Conclusion: In addition to the established HPV type 16, HPV 33 and 58 were consistently predictive of progression to CIN2+ over a five-year period in this cohort. These findings also support the utility of HPV risk groups to stratify women with non-16/18 hrHPV positivity who exhibit differential risks of progression. Additionally, HPV risk groups appear to predict progression regardless of age; thus, although hrHPV testing is not recommended for initial screening of women under 30 years of age, it may be a risk-stratification tool for these younger women, once a cervical abnormality is found. In conclusion, extended genotyping of non-16/18 hrHPV may be useful to identify individuals with normal or low-grade histology results who are at increased risk of progression to CIN2+, thereby improving the efficacy of cervical cancer screening. Citation Format: Alexandra Bukowski, Cathrine Hoyo, Michael G. Hudgens, Wendy R. Brewster, Fidel Valea, Rex C. Bentley, Adriana C. Vidal, Rachel L. Maguire, John W. Schmitt, Susan K. Murphy, Kari E. North, Jennifer S. Smith. Extended human papillomavirus genotyping to predict progression to high-grade cervical precancer: A prospective cohort study in the southeastern United States [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2230.

Women with a positive high-risk human papillomavirus (HPV) test remain at increased risk of HPV infection and cervical precancer ≥15 years later

Little is known about the long-term association between high-risk human papillomavirus (hrHPV) test results in women participating in a hrHPV-based cervical cancer screening program. To address this question, we collected data of 2217 women who participated in the POBASCAM hrHPV-based screening trial (enrolment 1999/2002) and also attended the Dutch hrHPV-based screening program between January 2017 and March 2018. Among 143 women who tested hrHPV-positive in 1999/2002, 45 (31.5%) had ≥ CIN2 or hysterectomy before 2017 and 17 (11.9%) tested hrHPV-positive at the 2017/2018 screen. In comparison, among 2074 women who tested hrHPV-negative in 1999/2002, 10 (0.5%) had ≥ CIN2 or hysterectomy before 2017 and 119 (5.7%) tested hrHPV-positive at the 2017/2018 screen. It follows that in the group of women who were not treated for ≥ CIN2 or had a hysterectomy in between the two screens 15 years apart (N = 2162), women who were hrHPV-positive in 1999/2002 had a higher risk of being hrHPV-positive in 2017/2018 than those who were hrHPV-negative in 1999/2002 (OR 3.4, 95% CI 1.8–6.1). A similar association was found at the genotype level for genotype-concordant results (5.1, 1.0–11.3) and for genotype non-concordant results (3.7, 1.6–6.7). Women who were hrHPV-positive in 2017/2018 had a higher risk of CIN3 after a hrHPV-positive result in 1999/2002 than after a hrHPV-negative result (5.8, 1.0–27.8). In conclusion, a positive hrHPV result in screening gives a long-term increased risk of a hrHPV-positive result, also for different genotypes, and a long-term increased risk of CIN3. This supports the concept of risk-stratification in hrHPV-based cervical cancer screening where previous hrHPV results are included in screening recommendations.

Superficial spreading cervical squamous cell carcinoma in situ involving the endometrium: a case report and review of the literature

BackgroundThe spread of cervical squamous cell carcinoma to the inner surface of the uterus with replacement of the endometrium is rare. Continuity of the lesion must be demonstrated to confirm superficial spread and rule out concomitant endometrial cancer.Case presentationWe present the case of a 66-year-old white woman with superficial spreading squamous cell carcinoma of the cervix that involved the endometrium. Her relevant past history included conization of the cervix to treat cervical intraepithelial neoplasia III with positive margins. She subsequently had three negative cervical vaginal cytology results, each with a positive high-risk human papillomavirus test. Transvaginal ultrasound showed occupation of the entire uterine cavity by dense material consistent with pyometra in addition to myometrial thinning due to tension and cervical dilation. The patient presented with greenish vaginal discharge of 3 months’ duration. The cervix was not visible during speculum examination. Access for endometrial sampling was not possible, raising suspicion of post-conization cervical stenosis. The patient was treated with laparoscopic hysterectomy with double adnexectomy. Histologic examination showed superficial squamous cell carcinoma invading the cervix to a depth of 2.8 mm; superficial spreading squamous cell carcinoma in situ was also observed in the lower uterine segment and endometrium. The patient was free of symptoms 12 months after surgery.ConclusionsSquamous cell carcinoma of the cervix with superficial spread to the endometrium is not included in the 2020 (fifth edition) World Health Organization Classification of Female Genital Tract Tumors or the 2018 International Federation of Gynecology and Obstetrics cervical cancer staging system. More clinical cases are needed to identify other prognostic factors and inform clinical practice guidelines on the management of this disease.

Early Mini-Invasive Treatment of Persistent Cervical Dysplasia: Clinical Outcome and Psycho-Relational Impact.

IntroductionAfter the diagnosis of L-SIL, 77. 3% had a persistent infection and anomalous Pap Test results. Many of these patients had highlighted psychological consequences such as anxiety, hypochondria, fear of cancer, and sexual problems. Several studies suggested that the clearance of HR-HPV infection could be accelerated by cervical excisional procedures, especially in L-SIL. In consideration of the psychological implications for HPV infection and related dysplasia in patients with CIN1 at PAP-smear and HR-HPV positivity at least for 6 months, we decided to plan a prospective study where we tried to anticipate excisional cervical using a minimally invasive treatment: thin loop electrosurgical excision procedure (t-LEEP). This study aims to analyze the clearance of HR-HPV after 6 and 12 months, clinical outcomes related to t-LEEP, and the psycho-relational impact at 12 months after t-LEEP.Materials and MethodsWe enrolled patients with the diagnosis of L-SIL at PAP-smear and HR-HPV positivity with a persistent CIN 1 (at least for 6 months), confirmed by cervical biopsy. All enrolled patients underwent t-LEEP. We followed prospectively and performed for all patients the HPV DNA test at 6 (T1) and 12 months (T2) and STAI-Y and FSFI scores at T0 and T2.ResultsWe prospectively enrolled 158 patients, 22 are excluded for the established criteria. Patients with HR-HPV and CIN 1 lesions treated with t-LEEP had an overall clearance of 83.8% at T2. In subgroups analysis at T2, we had a regression: in smoker 71.8%, in contraceptive users 69.5%, in patients aged <25 years 100%, aged 25–30 years 85%, aged 30–35 years 94.4%, aged 35–40 years 92%, and aged ≥40 years 89.1%, in HPV-16 96.4%, in HPV-53 89.5%, in HPV-18 87.5%, in HPV-31 86.6%, and in coinfected 3.5%. STAI-Y and FSFI after t-LEEP (T2) were statistically significant, reducing anxiety status and improving sexual function.ConclusionBased on these results, the use of t-LEEP in patients with persistent CIN 1 and HPV-HR at least for 6 months could be useful for accelerating HPV-HR clearance, in particular, for a subpopulation patient with an increased risk of progression and/or patients with psychological and sexual consequences of carrying an HR-HPV infection.

Effects of HPV Positivity in Women on Couples Sexual Behavior

We aimed to analyze the effect of HPV positivity in women, on women’s psychology, sexual health, and male sexuality. Participants in the study were sexually active patients with high-risk HPV positivity and without any cancerous and precancerous lesions in the pathological examination. Participants and their partners’ sexual health were evaluated with the FSFI questionnaire and the International Index of Erectile Function (IIEF) Score. The Beck anxiety inventory (BAI) form was used to determine participants’ anxiety status. The presence of premature ejaculation was analyzed using the premature ejaculation diagnosis tool (PEDT) form. Comparison of FSFI scores at the time of diagnosis and one month later revealed a significant decrease (18.1 vs 15.1, p = 0.001). Partners’ IEFF score decreased from 27.7 at diagnosis to 25.5(p = 0.001). The mean BAI score rose from 13.9 at diagnosis to 25.5 one month later (p = 0.001). Participants’ partners had a significantly worse PEDT score one month after diagnosis (6.0 vs 10.8, p = 0.001). The present study demonstrated a significant deterioration in female psychological and sexual health caused by HPV positivity. Moreover, after their partner’s diagnosis with HPV positivity, men were significantly more likely to suffer from erectile dysfunction and premature ejaculation.

Evaluation of High-Risk Human Papillomavirus Testing in Women with Atypical Squamous Cells of Undetermined Significance to Detect Cervical Intraepithelial Neoplasia

Introduction We retrospectively examined the changes in the management and outcomes of the cases with atypical squamous cells of undetermined significance (ASC-US) according to the Bethesda system (TBS). Materials and Methods Between May 2009 and December 2018, 432 cases with ASC-US were retrospectively examined for the implementation of high-risk human papillomavirus (hrHPV) testing and/or cervical biopsy and clinical courses. Results The hrHPV testing was performed in 277 cases (64.1%). Of these, there were 80 with positive hrHPV (28.9%). Of the 80 cases, cervical biopsy was performed in 71 (88.9%) cases based on the finding of colposcopy. Cervical intraepithelial neoplasia (CIN) was diagnosed in 55 cases (77.4%). The sensitivity, specificity, positive predictive value, and negative predictive value of CIN diagnosis by hrHPV testing in cases of ASC-US were 72.5, 95.0, 88.7, and 86.3%, respectively (p &lt; 0.01). Conclusion The conducting of hrHPV test on women who were evaluated as ASC-US according to TBS affirmed its clinical usefulness.

Correlation between Vaginal Microecological Status and Prognosis of CIN Patients with High-Risk HPV Infection.

Many microorganisms live in the vagina of healthy women. They interact with and compete with the microenvironment in the female vagina to form a dynamic balance of the microenvironment in the female vagina. However, imbalanced vaginal microecology can lead to vaginal resistance to pathogenic microorganisms. Poor capacity can cause women to develop infections of the reproductive tract. This article analyzes the vaginal microecological status of women with high-risk HPV infection for more than 6 months and healthy women and explores the risk factors that cause long-term high-risk HPV infection for timely detection and regulation of possible vaginal microecological imbalance in women with high-risk HPV infection for more than 6 months to prevent further development of cervical lesions in such patients. This article covers women with a sexual life history who attended the gynecology department of a hospital from January 2020 to September 2021. There were 280 patients in the experimental group: positive high-risk HPV; and there were 140 patients in the control group: negative high-risk HPV test. The correlation between vaginal microecology of CIN patients and patient prognosis according to the subject's vaginal microecology test results and prognosis of various levels of cervical lesions was analyzed. The experiment proved that the detection rate of normal vaginal microecology in the experimental group was 12.14% (34/280) compared with the detection rate of 29.29% (41/140) in the control group, and there was a trend of decrease, and the difference was statistically significant (χ2 = 17.23, P < 0.05). The detection rate of vaginal BV in the experimental group was 10.36% (29/280) compared with the detection rate of 5.0% (7/140) in the control group, and the difference was statistically significant (χ2 = 5.19, P < 0.05). This indicates that women with high-risk HPV infections for 6 months or longer have a higher incidence of vaginal microecological imbalances than healthy individuals and aggressive vaginal microecological screening. It is necessary to carry out the program. Detect and treat possible abnormal conditions in time to prevent the further onset of the disease.