Negative Human Papillomavirus Research Articles

Application of Machine Learning Algorithms for Risk Stratification and Efficacy Evaluation in Cervical Cancer Screening Among the ASCUS/LSIL Population: Evidence from the Korean HPV Cohort Study.

We assessed human papillomavirus (HPV) genotype-based risk stratification and the efficacy of cytology testing for cervical cancer screening in patients with atypical squamous cells of undetermined significance (ASCUS)/low-grade squamous intraepithelial lesion (LSIL). Between 2010 and 2021, we monitored 1,237 HPV-positive women with ASCUS/LSIL every 6 months for up to 60 months. HPV infections were categorized as persistent (HPV positivity consistently observed post-enrollment), negative (HPV negativity consistently observed post-enrollment), or non-persistent (neither consistently positive nor negative). HPV genotypes were grouped into high-risk (Hr) groups 1 (types 16, 18, 31, 33, 45, 52, and 58) and 2 (types 35, 39, 51, 56, 59, 66, and 68) and a low-risk group. Hr1 was subdivided into types a) 16 and 18; b) 31, 33, and 45; and c) 52 and 58. Cox regression and machine learning (ML) algorithms were used to analyze progression rates. Among 1,273 participants, 17.6% with persistent HPV infections experienced disease progression versus no progression in the HPV-negative group (p<0.001). Cox analysis revealed the highest hazard ratios (HRs) for Hr1-a (11.6, p<0.001), followed by Hr1-b (9.26, p<0.001) and Hr1-c (7.21, p<0.001). HRs peaked at 12-24 months, with Hr1-a maintaining significance at 24-36 months (10.7, p=0.034). ML analysis identified the final cytology change pattern as the most significant factor, with 14-15 months the optimal time for detecting progression from the first examination. In ASCUS/LSIL cases, follow-up strategies should be based on HPV risk types. Annual follow-up was the most effective monitoring for detecting progression/regression.

Promise and Perils of Primary HPV Testing.

Cervical cancer screening has reduced morbidity and mortality in many countries, but efforts to optimize screening modalities and schedules are ongoing. Using data from a randomized trial conducted in British Columbia, Canada, in conjunction with a provincial screening registry, Gottschlich and colleagues demonstrated that the estimated risk for precancerous disease (cervical intraepithelial neoplasia grades 2 or worse) at 8 years following a negative human papillomavirus (HPV) test was similar to the current standard of care (Pap testing after 3 years). The study supports extending screening intervals for those with a negative HPV test beyond currently recommended 5-year intervals. In an ideal world, the resources saved through less frequent routine cervical screening could be redirected to increasing screening uptake and follow-up of abnormalities to improve equity in cervical cancer prevention. However, implementation of extending screening intervals remains less than straightforward in settings with fragmented healthcare systems that lack information systems to support patient call/recall, such as the United States. To achieve the full promise of primary HPV testing, stakeholders at every level must commit to identifying and addressing the diverse spectrum of barriers that undergird existing inequities in care access, appropriately resource implementation strategies, and improve health information systems. See related article by Gottschlich et al., p. 904.

Identifying the intersection of parental HPV and COVID-19 vaccine hesitancy to inform health messaging interventions in community-based settings

PurposeParental human papillomavirus (HPV) vaccine hesitancy contributes to delays or refusals in adolescent uptake. It is unclear if COVID-19 vaccine hesitancy has further impacted the low HPV vaccine uptake trends among underrepresented minorities. This study examines the relationship between COVID-19 vaccine intent and HPV vaccine hesitancy among parents for their adolescents in communities with low vaccine uptake in Los Angeles County. MethodsParents from a school-based academic enrichment program serving low-income, first-generation immigrant families completed an online cross-sectional survey to understand parental HPV vaccine hesitancy, adolescent HPV vaccine behavior, and attitudes towards other vaccines, including intent to receive COVID-19 vaccines. In March 2021, parents with children ages 9–17 years completed online surveys. Using multivariate logistic regression models, we examined whether low parent intent to vaccinate their adolescent against COVID-19 was associated with hesitancy to vaccinate against HPV. ResultsA total of 291 surveys were completed. Among parents with high HPV vaccine hesitancy for their adolescent, 33 % did not intend to vaccinate their adolescent against COVID-19 compared to 7 % among parents with low HPV vaccine hesitancy. Low parent intention to vaccinate adolescent against COVID-19 was associated with higher HPV vaccine hesitancy (p < 0.01) after controlling for parent nativity status, medical mistrust, receiving the flu vaccination and negative HPV information. DiscussionOur findings indicate associations between low parental COVID-19 vaccine intent and higher HPV vaccine hesitancy for their adolescent. Identifying community-relevant health interventions to address parental vaccine hesitancy across multiple child and adolescent vaccines may help to achieve equitable vaccine uptake.

A portable thermal ablation device for cervical cancer prevention in a screen-and-treat setting: a randomized, noninferiority trial

Implementing standard-of-care cryotherapy or electrosurgical excision to treat cervical precancers is challenging in resource-limited settings. An affordable technological alternative that is as effective as standard-of-care techniques would greatly improve access to treatment. This randomized controlled trial aims to demonstrate the noninferiority efficacy of a portable, battery-driven thermal ablation (TA) device compared to cryotherapy and electrosurgical excision (large loop excision of transformation zone (LLETZ)) to treat cervical precancer in a screen-and-treat program in Zambia. A total of 3,124 women positive on visual inspection with acetic acid and eligible for ablative therapy were randomized to one of the treatment arms. Human papillomavirus (HPV) testing was performed at baseline and at the follow-up. The primary outcome was treatment success, defined as either type-specific HPV clearance at the follow-up in participants positive for HPV at baseline, or a negative visual inspection with acetic acid test for those who had a negative HPV test at baseline. After a median follow-up of 12 months, treatment success rates were 74.0%, 71.1% and 71.4% for the TA, cryotherapy and LLETZ arms, respectively, thus demonstrating noninferiority (P = 0.83). TA was a safe and well-accepted procedure. Only 3.6% of those randomized to TA reported moderate-to-severe pain, compared to 6.5% and 1.9% for the cryotherapy and LLETZ arms, respectively. Thus, our randomized controlled trial demonstrates the safety and efficacy of TA, which is not inferior to cryotherapy or surgical excision.ClinicalTrials.gov registration: NCT02956239.

Explainable prediction model for the human papillomavirus status in patients with oropharyngeal squamous cell carcinoma using CNN on CT images

Several studies have emphasised how positive and negative human papillomavirus (HPV+ and HPV−, respectively) oropharyngeal squamous cell carcinoma (OPSCC) has distinct molecular profiles, tumor characteristics, and disease outcomes. Different radiomics-based prediction models have been proposed, by also using innovative techniques such as Convolutional Neural Networks (CNNs). Although some of these models reached encouraging predictive performances, there evidence explaining the role of radiomic features in achieving a specific outcome is scarce. In this paper, we propose some preliminary results related to an explainable CNN-based model to predict HPV status in OPSCC patients. We extracted the Gross Tumor Volume (GTV) of pre-treatment CT images related to 499 patients (356 HPV+ and 143 HPV−) included into the OPC-Radiomics public dataset to train an end-to-end Inception-V3 CNN architecture. We also collected a multicentric dataset consisting of 92 patients (43 HPV+ , 49 HPV−), which was employed as an independent test set. Finally, we applied Gradient-weighted Class Activation Mapping (Grad-CAM) technique to highlight the most informative areas with respect to the predicted outcome. The proposed model reached an AUC value of 73.50% on the independent test. As a result of the Grad-CAM algorithm, the most informative areas related to the correctly classified HPV+ patients were located into the intratumoral area. Conversely, the most important areas referred to the tumor edges. Finally, since the proposed model provided additional information with respect to the accuracy of the classification given by the visualization of the areas of greatest interest for predictive purposes for each case examined, it could contribute to increase confidence in using computer-based predictive models in the actual clinical practice.

Counteracting HPV Cervical and Anal Infection through Dietary Supplementation of EGCG, Folic Acid, Vitamin B12 and Hyaluronic Acid: Clinical Case Reports.

Background: Human papilloma virus (HPV) infection and the management of its persistence is still a great medical challenge. Recently, scientific evidence has supported the potential therapeutic effects of four combined natural molecules-epigallocatechin gallate (EGCG), folic acid, vitamin B12 and hyaluronic acid (HA)-in counteracting HPV DNA positivity and related cytological lesions. Methods: Each patient of these five clinical cases had persistent HPV positivity in the anogenital site and assumed a dietary supplement based on a combination of 200 mg of EGCG, 50 mg of HA, 1 mg of vitamin B12 and 400 mcg of folic acid (Pervistop®, Farmares s.r.l., Rome, Italy) at a dosage of 1 or 2 caps/day for 6 or 3 months, respectively, depending on clinical history. Results: After treatment, all the patients reported a negative HPV DNA test and improved cytological lesions, thus demonstrating the ability of these combined molecules to counteract both anal and cervical HPV infection and related manifestations. Conclusions: Overall, these data corroborate previous evidence about the effectiveness of such natural molecules in the management of HPV infection and its persistence. Naturally, further studies with a larger population and long-term follow-up will contribute to reinforce the positive effects of this dietary supplement in counteracting HPV infection.

Pharmacological correction of immunological disorders in perimenopausal women with recurrent epithelial cervical dysplasia associated with human papillomavirus infection

Despite the successes achieved in implementing screening programs and treating diseases caused by human papillomavirus (HPV) infection, the frequency of cervical intraepithelial neoplasia (CIN) of moderate and high grades associated with high-risk human papillomavirus (HR-HPV) remains between 9% to 21%. Vaginal dysbiosis and the development of immunodeficient states due to persistent HR-HPV infection require effective immunomodulatory and antiviral therapy before cervical surgery in perimenopausal women with recurrent CIN II.The objective: to evaluate the effectiveness of antiviral and immunomodulatory therapy by determining the state of vaginal biocenosis, immunological status and papillomavirus load of the cervical mucosa before surgical treatment in perimenopausal women with recurrent CIN II.Materials and methods. A prospective study was conducted on 98 women aged 40 to 55 years old, including 60 patients with morphologically verified recurrent CIN II associated with high-risk HPV, forming the main group. The control group comprised 38 women with negative HPV test results and without significant gynecological or somatic pathology. In the main group, a complex consisting of a blend of plant extracts of sod pike grass (Deschampsia caespitosa), ground cinquefoil grass (Calamagrostis epigeios), and echinacea purpurea grass (Echinaceae purpureae) was administered orally.Vaginal microbiota was assessed using Hey-Іson criteria, and immunological status was examined in patients using solid-phase enzyme-linked immunosorbent assay to determine IgG, IgM, IgA antibodies in serum and cervical mucus, levels of interleukin-1β (IL-1β), interferons alpha (IFN-α), gamma (IFN-γ), tumor necrosis factor alpha (TNF-α). Additionally, the DNA of high-risk HPV in cervical mucosa was quantitatively assessed using real-time PCR. The investigations were conducted before and after the applied therapy.Results. The investigation of vaginal content revealed the presence of bacterial vaginosis in 65.0% of patients in the main group, the frequency of which decreased by 2 times after treatment, with the number of women with an intermediate type of vaginal content increasing by 2.8 times (51.7%) and those with normal microbiota increasing by 2.5 times. Disruptions in cellular and humoral immunity systems were identified. After treatment, there was an increase in viral load in the significant «threshold» category (3–5 lg) by 1.25 times and in the «above threshold for progression» category (&gt;5 lg) by 2.3 times, reflecting natural HPV clearance. No direct correlation was found between viral load activity and the degree of CIN or positive morphological changes regarding regression of cervical intraepithelial lesions.Conclusions. The use of a complex containing a blend of plant extracts of sod pike grass (Deschampsia caespitosa), ground cinquefoil grass (Calamagrostis epigeios), and echinacea purpurea grass (Echinacea purpureae) improves the state of vaginal biocenosis, indicators of cellular and humoral immunity, and promotes HPV elimination, it has adequate safety and tolerability, which determines the feasibility of its use in the complex treatment of cervical intraepithelial neoplasia at the preparatory stage before surgery and in the postoperative period to prevent complications and relapses.

Evidence of Decreased Long-term Risk of Cervical Precancer after Negative Primary HPV Screens Compared with Negative Cytology Screens in a Longitudinal Cohort Study.

The growing use of primary human papillomavirus (HPV) cervical cancer screening requires determining appropriate screening intervals to avoid overtreatment of transient disease. This study examined the long-term risk of cervical precancer after HPV screening to inform screening interval recommendations. This longitudinal cohort study (British Columbia, Canada, 2008 to 2022) recruited women and individuals with a cervix who received 1 to 2 negative HPV screens (HPV1 cohort, N = 5,546; HPV2 cohort, N = 6,624) during a randomized trial and women and individuals with a cervix with 1 to 2 normal cytology results (BCS1 cohort, N = 782,297; BCS2 cohort, N = 673,778) extracted from the provincial screening registry. All participants were followed through the registry for 14 years. Long-term risk of cervical precancer or worse [cervical intraepithelial neoplasia grade 2 or worse (CIN2+)] was compared between HPV and cytology cohorts. Cumulative risks of CIN2+ were 3.2/1,000 [95% confidence interval (CI), 1.6-4.7] in HPV1 and 2.7/1,000 (95% CI, 1.2-4.2) in HPV2 after 8 years. This was comparable with the risk in the cytology cohorts after 3 years [BCS1: 3.3/1,000 (95% CI, 3.1-3.4); BCS2: 2.5/1,000 (95% CI, 2.4-2.6)]. The cumulative risk of CIN2+ after 10 years was low in the HPV cohorts [HPV1: 4.7/1,000 (95% CI, 2.6-6.7); HPV2: 3.9 (95% CI, 1.1-6.6)]. Risk of CIN2+ 8 years after a negative screen in the HPV cohorts was comparable with risk after 3 years in the cytology cohorts (the benchmark for acceptable risk). These findings suggest that primary HPV screening intervals could be extended beyond the current 5-year recommendation, potentially reducing barriers to screening.

When cervical microglandular hyperplasia coincides with high-risk human papillomavirus infection: Diagnostic challenges and evidence

ABSTRACT Cervical microglandular hyperplasia (MGH) is a benign cervical lesion mimicking cervical malignancy, thereby making its pathogenesis diagnostically challenging for gynecologists and pathologists. While MGH is often associated with physiological or external hormonal factors, several cases remain unexplained. In this report, we present a case of a young primiparous woman without evident hormonal risk factors seeking gynecologic evaluation owing to abnormal vaginal discharge. During her clinical examination, we observed an irregular cervical lesion raising malignancy-related concerns and consequently planned a colposcopy. The human papillomavirus (HPV) polymerase chain reaction tested positive for two high-risk HPV genotypes (16 and 52), denoting that the patient did not have an HPV infection history. During colposcopy, we identified a friable papillary cervical mass at the transformation zone, bleeding significantly with minimal handling, from which we obtained multiple biopsies. Our subsequent histopathological examinations eventually confirmed the MGH diagnosis, ruling out malignancy. Intriguingly, a follow-up colposcopy 7 months later revealed the resolution of the initial cervical lesion, coinciding with negative HPV test and Pap smear cytology results. This case highlights the rare encounter of MGH concurrent with an initial high-risk HPV infection. Beyond a comprehensive review of related literature and clinical guidelines, we discuss the clinical and histopathological results in such a case.

Post-Conization HPV Vaccination and Its Impact on Viral Status: A Retrospective Cohort Study in Troms and Finnmark, 2022.

Human papillomavirus (HPV) is associated with cellular changes in the cervix leading to cancer, which highlights the importance of vaccination in preventing HPV infections and subsequent cellular changes. Women undergoing the loop electrosurgical excision procedure (LEEP), a treatment for high-grade cervical intraepithelial neoplasia (CIN2+), remain at risk of recurrence. This study assessed the effect of post-conization HPV vaccination on the viral status of women at six months post-conization, aiming to evaluate the vaccine's effectiveness in preventing recurrence of CIN2+. A retrospective cohort study was conducted among women in Troms and Finnmark who underwent conization in 2022. Using the SymPathy database and the national vaccination register (SYSVAK), we analyzed the vaccination statuses and HPV test results of women born before 1991, who had not received the HPV vaccine prior to conization. Out of 419 women undergoing conization, 243 met the inclusion criteria. A significant association was found between post-conization HPV vaccination and a negative HPV test at six months of follow-up (ARR = 12.1%, p = 0.039). Post-conization HPV vaccination significantly reduced the risk of a positive HPV test at the first follow-up, suggesting its potential in preventing the recurrence of high-grade cellular changes. However, the retrospective design and the insufficient control of confounding variables in this study underscore the need for further studies to confirm these findings.

Human Papilloma Virus Typing as a Triage Tool for Women with Postcoital Bleeding: A Retrospective Cohort Study.

Objective: To investigate the performance of human papilloma virus (HPV) typing as a triage tool in the management of patients with postcoital bleeding (PCB). Methods: All patients referred for colposcopy at a cervical pathology clinic of a nationwide health insurance organization, due to PCB and had a preceding high-risk HPV (hrHPV) test between 2018 and 2020, were retrospectively located. Demographic and pathologic data were collected from electronic medical files. Sensitivity, specificity, and negative and positive predictive value of hrHPV test according to final pathology were calculated. Results: Three hundred ninety patients referred for colposcopy due to PCB with a preceding hrHPV test were located. HrHPV-positive patients were significantly younger (33.7 ± 10 vs. 37.2 ± 9, p < 0.006) with a higher proportion of nulliparous, nonmarried, and smokers compared with hrHPV-negative patients (75% vs. 47%, p < 0.001; 75.4% vs. 45.1%, p < 0.001; and 24.6% vs. 12.8%, p < 0.028, respectively). No case of high-grade cervical intraepithelial neoplasia (CIN2/3) was identified among hrHPV-negative patients. The sensitivity and NPV of the hrHPV test for high-grade cervical lesions were both 100%, decreasing to 36% and 95%, respectively, for any cervical dysplasia (CIN1/CIN2/CIN3). Adding cytology to HPV typing had a negligible effect on test performance. At univariate analysis, age, HPV vaccine status, nulliparity, and positive HPV typing were independently associated with cervical dysplasia. At multivariate analysis, only positive HPV typing remained significantly associated with cervical dysplasia (hazard ratio 2.75, confidence interval 1.1-6.5, p = 0.023). Conclusion: A negative HPV test even in the presence of PCB may rule out cervical dysplasia with extremely high accuracy and may save unnecessary colposcopies.

The role of cervical elastography in the differential diagnosis of preinvasive and invasive lesions of the cervix.

This study aims to evaluate the role of cervical elastography in the differential diagnosis of preinvasive and invasive lesions of the cervix. A total of 95 women participated in this prospective study and were divided into the following groups: 19 healthy subjects (group 1) with normal cervicovaginal smear (CVS) and negative human papillomavirus test (HPV DNA), 19 women with normal cervical biopsy and normal final pathological result of cervical biopsy (group 2), 19 women with low-grade squamous intraepithelial lesion (LSIL) (group 3), 19 women with high-grade squamous intraepithelial lesion (HSIL) (group 4), and 19 women with cervical cancer (group 5). Clinical, demographic, histopathological, and elastographic results were compared between these groups. Comparing groups, age (40.42 ± 8.31 vs. 39.53 ± 8.96 vs. 38.79 ± 9.53 vs. 40.74 ± 7.42 vs. 54.63 ± 12.93, p < 0.001 respectively), gravida (1.74 ± 1.33 vs. 2.16 ± 1.68 vs. 2.21 ± 1.96 vs. 2.53 ± 1.93 vs. 4.63 ± 2.17 p < 0.001 respectively), parity (1.37 ± 0.68 vs. 1.68 ± 1.20 vs. 1.58 ± 1.30 vs. 2.00 ± 1.67 vs. 3.37 ± 1.61, p < 0.001 respectively), and the proportion of patients at menopause (10.5% vs., 15.8% vs. 10.5% vs. 5.3% vs. 57.9%, p < 0.01 respectively), a statistically significant difference was found (Table1). However, no statistically significant difference was found in the number of abortions, BMI, mode of delivery, smoking, additional disease status, history of surgery, and family history (p > 0.05) (Table2. As a result of the applied roc analysis, mean cervical elastographic stiffness degree (ESD) was found to be an influential factor in predicting cervical cancer (p < 0.05). The mean cut-off value was 44.65%, with a sensitivity of 94.7% and a specificity of 96.1% (Table7). Measurement of ESD by elastography is a low-cost, easily applicable, and non-invasive indicator that can distinguish cervical cancer from normal cervical and preinvasive lesions. However, it is unsuitable for determining preinvasive cervical lesions from normal cervix.

Efficacy of Cobas HPV testing for predicting grade 2+ cervical intraepithelial neoplasia in a cancer prevention center and a gynecologic oncology clinic: A single-institution experience.

To evaluate the efficacy of Cobas human papillomavirus (HPV) testing to predict cervical intraepithelial neoplasia of grade 2 or higher (CIN2+), Cobas HPV testing results were correlated with follow-up biopsy in patients from Cancer Prevention Center (CPC) and Gynecologic Oncology Clinic (GOC) of The University of Texas MD Anderson Cancer Center. Institutional data for patients who underwent Cobas HPV and Papanicolaou (Pap) cytology cotesting from 2019 to 2020 were retrospectively reviewed. Surgical follow-up results were compared with Cobas HPV testing results in two populations. A total of 2226 patients, including 921 women (mean age, 55.2years) seen at the CPC and 1305 women (mean age, 49.3years) seen at the GOC, were included. Specimens from GOC patients had a significantly higher HPV positivity rate than did those from CPC patients (22.9% vs. 10.1%; p<.001). Cobas HPV testing was positive in all seven CPC patients with surgical follow-up results showing CIN2+. Among 36 GOC patients with CIN2+ lesions, five patients had HPV-/Pap+testing results. Although only seven CPC patients had CIN2+, Cobas HPV testing showed 100% sensitivity for predicting CIN2+ in this group. Sensitivity for CIN2+ was 86.5% in the GOC group, whereas 13.9% of GOC patients with CIN2+ had negative HPV testing results. Cobas HPV testing was highly efficacious for predicting CIN2+ lesions in the low-risk CPC population, which supports HPV primary screening for cervical cancer in low-risk populations. For high-risk patients, especially those with a history of CIN2+/cervical cancer, HPV/Pap cotesting may still be necessary to maintain a high clinical sensitivity for CIN2+.

Prevalence of Human Papillomavirus Infection and Cervical Abnormalities among Women Attending a Tertiary Care Center in Saudi Arabia over 2 Years.

Human papillomavirus (HPV) genotype distribution varies according to the assessment method and the population targeted. This study aimed to assess HPV infection prevalence in women aged 23 to 82 with abnormal cytology attending King Fahad Medical City (KFMC), Riyadh, Saudi Arabia, using retrospective data collected from January 2021 to December 2022. Cytological distribution included 155 samples of atypical squamous cells of undetermined significance (ASCUS) (n = 83), low-grade squamous intraepithelial lesion (LSIL) (n = 46), high-grade squamous intraepithelial lesion (HSIL) (n = 14), atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion (ASC-H) (n = 10), and squamous cell carcinoma (SCC) (n = 2). All samples were submitted to HPV detection and genotyping using Xpert HPV assay specimens. The most prevalent epithelial abnormalities were ASCUS (53.50%). Positive HPV infection results were observed in 52.9% of the samples. The highest prevalence of HPV genotypes, accounting for 31%, was attributed to the other high-risk genotypes, including 31, 33, 35, 39, 51, 52, 56, 58, 59, 66, and 68, followed by high-risk genotype 16, which counted in 11.60% of cases. Individuals who tested positive for HPV 16 were at a high risk of ASC-H, HSIL, and LSIL. Those testing positive for HPV 18-45 exhibited an elevated risk of LSIL, and those with positive results for other high-risk HPV genotypes were at an increased risk of ASCUS and LSIL, suggesting a low oncogenic potential. The results suggest that the percentage of association between samples with abnormal cervical presentation and negative high-risk HPV diagnosis is noticeably increasing. This underscores the need for effective screening programs and an understanding of the impact of specific HPV genotypes on cervical abnormalities.

A qualitative study of primary care clinician’s approach to ending cervical cancer screening in older women in the United States

The United States Preventive Services Task Force (USPSTF) recommends that cervical cancer screening end in average-risk patients with a cervix at 65 years of age if adequate screening measures have been met, defined as having 1) at least three normal consecutive cytology (Pap) tests, or 2) two normal cytology tests and/or two negative high-risk human papillomavirus tests between ages 55–65; the last test should be performed within the prior 5 years. Up to 60 % of all women aged 65 years and older who are ending screening do not meet the criteria for adequate screening. The objective of this study was to understand the process and approach that healthcare clinicians use to determine eligibility to end cervical cancer screening. In 2021 we conducted semi-structured interviews in San Francisco, CA with twelve healthcare clinicians: two family medicine physicians, three general internal medicine physicians, two obstetrician/gynecologists and five nurse practitioners. Thematic analysis, using inductive and deductive coding, was utilized. Three major themes emerged: following guidelines, relying on self-reported data regarding prior screening, and considering sexual activity as a factor in the decision to end screening. All interviewees endorsed following the USPSTF guidelines and they utilized self-report to determine eligibility to end screening. Clinicians’ approach was dependent in part on their judgement about the reliability of the patient to convey their screening history. Sexual activity of the patient was considered when making clinical recommendations. Shared decision-making was often utilized. Clinicians voiced a strong reliance on self-reported screening history to end cervical cancer screening.

Risk Profile of High-grade Cervical Lesions and Cervical Cancer Considering the Combination of Cytology, HPV Genotype, and Age among Women Undergoing Colposcopy.

The present study aims to establish a risk profile for high-grade cervical lesions and cervical cancer (CIN2 + ) in women undergoing colposcopy at the Hospital do Câncer de Barretos, through the analysis of Human Papillomavirus (HPV) infection, cervical cytology, and patient's age. Retrospective cross-sectional study based on a computerized database of women aged ≥ 18 years old who underwent colposcopy at the Prevention Department of the Hospital do Câncer de Barretos from 2017 to 2019. A total of 3,411 women were included, 58.0% were positive for high-risk-HPV test, with a higher prevalence of CIN2+ for HPV16 (30.3%) and other HPV (45.0%). Cytological findings that suggest invasive cervical cancer (squamous cells or adenocarcinoma), regardless of the status of HPV test, showed 100% diagnosis of CIN2 + , while atypias that suggest high-grade lesions, HSIL and ASC-H, positive for HPV test, showed in 86 and 55.2%, respectively, diagnosis of CIN2 + . ASC-H cytological results among women aged > 40 years old and negative HPV were mainly associated with benign findings. We observed that ≤ CIN1 has a higher prevalence among older women with negative HPV, while for high-grade lesions there is an increase among young women HPV16- and/or 18-positive. In cancer diagnosis, we observed a predominance of HPV 16/18 regardless of the age group. The highest risks of precursor lesions and cervical cancer were found among women with positive HPV 16/18 tests and severe cytological atypia in population screening tests. In addition, cytological findings of ASC-H HPV negative in women > 40 years old usually represent benign findings in histological investigation.

Unveiling Hidden Risks: Intentional Molecular Screening for Sexually Transmitted Infections and Vaginosis Pathogens in Patients Who Have Been Exclusively Tested for Human Papillomavirus Genotyping.

This analytical, prospective, cross-sectional study included 408 males and females. Eligible participants had positive and negative HPV genotyping test results and agreed to early detection or had HPV antecedents. They provided the same urogenital samples used for HPV detection and, through our multiplex in-house PCR assay, we screened for Candida spp., Ureaplasma spp., Trichomonas vaginalis, Neisseria gonorrhoeae, Chlamydia trachomatis, herpes simplex virus 1 and 2 (HSV), Mycoplasma spp., molluscum contagiosum virus (MCV), Treponema pallidum, Haemophilus spp., Staphylococcus aureus, and Klebsiella spp. The subsequent statistical analysis aimed to reveal correlations between HPV genotypes and the identified pathogens. Of the participants, 72.1% (n = 294) tested positive for HPV genotypes. HR-HPV (high-risk HPV) genotypes comprised 51 (8.1%), 66 (7.1%), and 58 (6.1%). Haemophilus spp., Ureaplasma spp., Candida spp., Staphylococcus aureus, and Mycoplasma spp. frequently co-occurred with HPV infection (p < 0.05). Gender-based variations were notorious for Ureaplasma spp., Mycoplasma spp., and MCV (p < 0.05). Coinfections were prevalent (43.9%), with a positive HPV result elevating the risk for Trichomonas vaginalis, Mycoplasma spp., Staphylococcus aureus, HSV, and MCV (OR > 1, p < 0.05). HPV 16 correlated with HSV and Ureaplasma spp., while HPV 6 was linked with HSV and MCV (p < 0.05). This screening strategy uncovered significant coinfections and associations between HPV genotypes and pathogens, underscoring the importance of routine screening to explore clinical implications in urogenital health.

The Role of Human Papilloma Virus in the Pathogenesis of Sinonasal Inverted Papilloma; A Metanalytical Study

Abstract Background Sinonasal inverted papilloma (SNIP) is a benign and relatively rare tumor of the nasal cavity and paranasal sinuses, most commonly originates from the lateral nasal wall or maxillary sinus from the schneiderian sinonasal epithelium. There is a male predominance with a male-to-female ratio of 3.4:1. Sinonasal Squamous Cell Carcinoma (SCC) associated with IP has an incidence of approx. 0.38 cases/million persons/year. Patients with carcinoma in IP are older than those IP patients without carcinoma. Some authors assume an influence of Human Papilloma Virus (HPV) subtyping. Transcripts of HPV DNA were found in malignant IP. Objective To perform a meta-analytical study to determine the relationship between human papilloma virus and the occurrence of sinonasal inverted papilloma. Patients and Methods The review will be restricted to RCTs, clinical trials, and comparative studies, either prospective or retrospective, which studied the outcome of Negative HPV group versus Positive HPV group of patients. Data Sources Medline databases (PubMed, Medscape, ScienceDirect. EMF-Portal) and all materials available in the Internet till 2021. Data Extraction If the studies did not fulfill the inclusion criteria, they were excluded. Study quality assessment included whether ethical approval was gained, eligibility criteria specified, appropriate controls, and adequate information and defined assessment measures. Results In our study HPV positive cases were (23.6%) (107/ 452) among SNIP patients. Malignant SNIP rate was (10.8%) (49/ 452). HPV positive cases among malignant SNIP patients was (51.02%) (25/49). Conclusion In this meta-analytical study HPV positive cases were (23.6%) (107/ 452) among SNIP patients. Malignant SNIP rate was (10.8%) (49/ 452). Though the etiology of SNIP remains controversial, the studies reviewed in this study indicate a role for HPV infection. Further studies in the future regarding the impact of other risk factors on the occurrence of SNIP would be of value, these factors include angiogenic factors, environmental factors, genetic, viral and chronic sinonasal inflammation.

P16INK4a and pRb expression in laryngeal squamous cell carcinoma with and without infection by EBV or different genotypes of HPV: a retrospective study

BackgroundLaryngeal squamous cell carcinoma (LSCC) represents one of the principal tumors of the head and neck. Human papillomavirus (HPV) and Epstein–Barr virus (EBV) are considered risk factors for the development and the clinical prognosis of LSCC. High levels of p16INK4a are suggested as a surrogate marker of HPV or EBV infection in some head and neck tumors but in LSCC is still controversial. Furthermore, pRb expression may be considered an additional biomarker but it has not been clearly defined. This work aimed to compare the expression of pRb and p16INK4a as possible biomarkers in tumor tissues with and without infection by EBV or different genotypes of HPV from patients with LSCC.MethodsTumor samples from 103 patients with LSCC were previously investigated for the presence and genotypes of HPV using the INNO-LiPA line probe assay and for the infection of EBV by qPCR. p16 INK4a and pRb expression was assessed by immunohistochemistry.ResultsOf the 103 tumor samples, expression of p16INK4a was positive in 55 (53.4%) and of this, 32 (56.1%) were positive for HPV whereas 11 (39.3%) were EBV positive but both without a significantly difference (p > 0.05). pRb expression was positive in 78 (75.7%) and a higher frequency of this expression was observed in HPV negative samples (87.0%) (p = 0.021) and in high-risk HPV negative samples (85.2%) (p = 0.010). No difference was observed when comparing pRb expression and EBV infection status (p > 0.05).ConclusionOur results support the suggestion that p16INK4a is not a reliable surrogate marker for identifying HPV or EBV infection in LSCC. On the other hand, most of our samples had pRb expression, which was more frequent in tumors without HPV, suggesting that pRb could indicate HPV negativity. However, more studies with a larger number of cases are required, including controls without LSCC and evaluating other molecular markers to determine the real role of p16INK4a and pRb in LSCC.

Programmed death-ligand 1 and p53 as a biomarker in predicting oropharyngeal squamous cell carcinoma

Introduction. Currently, the pathogenetic role of the human papillomavirus (HPV) in carcinogenesis is well studied, that most cases of oropharyngeal squamous cell carcinoma are associated with the persistence of this infection. In addition to HPV infection, the involvement of programmed death-ligand 1 (PD-L1) and p53 proteins in the initiation and progression of oropharyngeal squamous cell carcinoma provides their formation as additional biomarkers in predicting the disease.Aim. To study the prognostic role of PD-L1 and p53 expression in oropharyngeal squamous cell carcinoma depending on HPV status.Materials and methods. The study included 62 patients with oropharyngeal squamous cell carcinoma T1–4N0–3M0 (Tumor, Nodus and Metastasis, (TNM), 7th edition) treated in 2015–2020 at the Republican Specialized Scientific and Practical Medical Center of Oncology and Radiology and in the Tashkent and Samarkand city branches. All patients underwent immunohistochemical analysis for the presence of p16INK4a, PD-L1 and p53 protein expression in formalin-fixed and paraffin-embedded tumor tissue samples.Results. Based on the results of the assessment, it was found that positive HPV status, low and medium levels of PD-L1 expression and positive regulation of wild-type p53 are associated with favorable outcomes in patients with oropharyngeal squamous cell carcinoma. Negative HPV status, high and very high levels of PD-L1 expression, loss of wild type p53 function with upregulation of p53 mutant type leads to worse disease outcomes.Conclusion. Thus, the assessment of the expression of the onco-suppressor protein p53 helps to determine the biology of cancer cells in patients with oropharyngeal squamous cell carcinoma and suggest sensitivity to ongoing therapy, and by studying the regulation of the PD-L1 protein, antitumor immune regulation can be suggested in these patients.