Choosing the Appropriate HPV Testing and Treatment Algorithm: What Works for Different Contexts?

Cervical cancer can be eliminated, and the global community intends to achieve this goal in the next century. For this to successfully occur, concerted efforts to implement and scale-up available, evidence-based strategies including human papillomavirus vaccination, screening and treatment of precancerous lesions, and early detection and treatment for invasive cancers is paramount. While the World Health Organization has offered technical guidance and recommendations on implementation, several questions remain unanswered and require urgent high-quality research to inform policy and practice. We discuss the findings from the Cervical Cancer Screening and Treatment Algorithms pilot study in the context of the evidence synthesis conducted for the second edition of the World Health Organization guidelines for screening and treatment of cervical precancer lesions for cervical cancer prevention. Policymakers at the national level must consider the weight of evidence with country-level resources to make decisions on screening, triage, and treatment approaches. See related article by Sebitloane et al., p. 779.

Clinical evaluation of primary human papillomavirus (HPV) testing with extended HPV genotyping triage for cervical cancer screening: A pooled analysis of individual patient data from nine population-based cervical cancer screening studies from China.

OBJECTIVE: To assess the clinical values of extended human papillomavirus (HPV) genotyping in triage of high-risk HPV-positive women, focusing on the trade-off between cervical precancer detections and colposcopy referrals. METHODS: A bivariate random-effects model was used to estimate the diagnostic accuracy of primary HPV screening with following triage strategies to detect cervical precancers: (i) partial genotyping for HPV16/18 combined with cytological testing at atypical squamous cells of undetermined significance threshold (used as the comparator), (ii) genotyping for HPV16/18/58/52, (iii) genotyping for HPV16/18/58/52/33, (iv) genotyping for HPV16/18/58/33/31, (v) genotyping for HPV16/18/58/52/33/31, and (vi) genotyping for HPV16/18/58/52/33/31/39/51. Internal risk benchmarks for clinical management were used to evaluate the risk stratification of each triage strategy. RESULTS: A total of 16,982 women (mean age 46.1 years, range 17-69) were included in this analysis. For CIN3+ detection, triage with HPV16/18/58/33/31 genotyping achieved lower positivity (6.85% vs. 7.35%, p = 0.001), while maintaining similar sensitivity (91.35% vs. 96.42%, p = 0.32) and specificity (94.09% vs. 93.67%, p = 0.56) compared with the comparator strategy. Similar patterns were observed for CIN2+ detection. Women with a positive HPV16/18/58/33/31 genotyping test had high enough risk for CIN3+ for colposcopy referral, while the risk for women with a negative test was below the 1-year return decision threshold according to internal benchmarks. CONCLUSIONS: Our findings suggested extended HPV genotyping is of potential to be used as a triage technique integrated into HPV-based cervical cancer screening, leading to reduced need for colposcopy referral while maintaining similar disease detection and efficient risk stratification.

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

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

Precancerous cervical lesion and associated factors among HIV-infected women in Ethiopia: systematic review and meta- analysis.

BACKGROUND: Despite several preventative and control measures Ethiopia continues to see an increase in cervical cancer. Comprehensive evidence is very important to suggest ministry of health. Therefore, the aim of this study is to estimate the pooled violence of Precancerous Cervical Lesion and to identify associated factors among women living with HIV AIDS in Ethiopia. METHODS: From February 15, 2024 to March 17, 2024, systematic and methodical search of the literature was conducted using electronic databases such as PubMed, HINARI, Global Health, Scopus, EMBASE, Web of Science, African Journal online (AJOL), and Google Scholar. Quality appraisal was assessed based on Joanna Briggs Institute (JBI) critical appraisal checklist for analytical cross-sectional study using 9 criteria. The Cochrane Q and I2 test statistics were used to verify the heterogeneity of the studies. Using a fixed effect model, the pooled estimate prevalence of precancerous cervical lesion among women living with HIV was calculated. RESULTS: After reviewing 9,470 studies, 9 studies involving 2,910 women with HIV were included. The pooled estimate of precancerous cervical cancer among women living with HIV in Ethiopia was 15.34% (95% CI: 8.97, 21.72). Having history of sexual infection (POR = 3.12; 95% CI: 1.38, 7.05), having multiple sexual partner (POR = 3.14; 95% CI: 2.29, 4.30), and parity greater than two (POR = 4.97; 95% CI: 3.17, 7.78) were identified factors associated with precancerous cervical lesion. CONCLUSION: This study found that about one-six of HIV-positive women developed precancerous cervical lesion. According to this study, there was a substantial correlation between precancerous cervical lesion among HIV-positive women and having history of sexually transmitted infection, having multiple sexual partners, and being multipara. In order to reduce precancerous cervical lesion, FMOH, policy makers, and interested parties should pay particular attention to this issue.

High-Risk Human Papilloma Virus Genotype Distribution and Correlation with Cervical Cytomorphological Data in Turkish and Immigrant Women in Mersin Province.

Human papilloma virus (HPV) is the most common sexually transmitted viral agent in the world and the most common cause of cervical cancer. HPV prevalence and genotype distribution vary by region and demographic data. In a province in the south of Turkey that constantly receives immigration, we aimed to determine the prevalence of high-risk HPV (HR-HPV) genotypes, evaluate the compatibility between cervical Pap smear cytology results patients and HR-HPVs, and make an up-to-date contribution to the elucidation of epidemiological data. In this single-centre study, a total of 12,641 women aged 18 and over were evaluated retrospectively from January 2019 to July 2022. HPV detection and genotyping were analysed by the PCR method. Bethesda scoring was used for Pap smear cytological evaluation. The overall prevalence of HR-HPV was 12.6% (12.7% in Turkish women, 11.2% in foreign women). Among the typed HPVs that were detected, HPV-16 (31%) was found first, followed by HPV-18 (8%). The prevalence of HR-HPV was higher in women with abnormal cytology (977/1762, 55.4%) than in women with normal cytology (620/10879, 5.7%) (p<0.001). Turkey doesn't yet have a national HPV immunisation program. We think that determining the specific regional frequency of other HR-HPVs separately will be useful in the follow-up of the natural course of the type-specific infection and in vaccine studies in the future.

Culturally Competent Education and Human Papillomavirus Self-Sampling Achieves Healthy People 2030 Cervical Screening Target Among Low-Income Non-Hispanic Black and Hispanic Women.

PURPOSE: Disparities in cervical cancer screening, incidence, and mortality exist in the United States. Cervical cancer incidence and mortality rates in Texas are 20% and 32% higher, respectively, than national averages. Within Texas, these rates are significantly higher among non-Hispanic (NH) Black and Hispanic women. Cervical cancer screening uptake is lower among NH Black and Hispanic women (72.9% and 75.9%, respectively) compared with White women (85.5%) in Texas. METHODS: During March-August 2023, we conducted a pilot study that offered culturally competent education and human papillomavirus (HPV) self-sampling kits to women in two public housing projects in Houston, TX, that have predominantly NH Black or Hispanic residents. Among those eligible for cervical cancer screening, 35% (n = 24) of the NH Black and 34% (n = 16) of the Hispanic women were found to be underscreened per the US Preventive Services Task Force Guideline. We recruited 40 (24 NH Black and 16 Hispanic) eligible women for our study. The study was approved by the MD Anderson institutional review board and registered with ClinicalTrials.gov (NCT04614155-March 11, 2020). RESULTS: Seventy-five percent of the NH Black and 87% of the Hispanic participants completed the HPV self-sampling procedures per protocol. Samples of 17% NH Black and 12% Hispanic participants showed a performance error. Overall, cervical cancer screening uptake improved from 65% to 91% among NH Black and from 66% to 96% among Hispanic participants. CONCLUSION: Culturally competent education and HPV self-sampling resulted in remarkable improvement in cervical cancer screening uptake among underscreened NH Black and Hispanic women residents of Houston public housing projects. Implementing this strategy could significantly reduce cervical cancer incidence and mortality among similar populations in the United States and globally.

HPV genotyping in clinical samples using long-read single-molecule real-time sequencing.

Human papillomavirus (HPV) genotyping is widely used, particularly in combination with high-risk (HR) HPV tests for cervical cancer screening. We developed a genotyping method using sequences of approximately 800 bp in the E6/E7 region obtained by PacBio single molecule real-time sequencing (SMRT) and evaluated its performance against MY09-11 L1 sequencing and after the APTIMA HPV genotyping assay. The levels of concordance of PacBio E6/E7 SMRT sequencing with MY09-11 L1 sequencing and APTIMA HPV genotyping were 100% and 90.8%, respectively. The sensitivity of PacBio E6/EA7 SMRT was slightly greater than that of L1 sequencing and, as expected, lower than that of HR-HPV tests. In the context of cervical cancer screening, PacBio E6/E7 SMRT is then best used after a positive HPV test. PacBio E6/E7 SMRT genotyping is an attractive alternative for HR and LR-HPV genotyping of clinical samples. PacBio SMRT sequencing provides unbiased genotyping and can detect multiple HPV infections and haplotypes within a genotype.

Changes in intrahost genetic diversity according to lesion severity in longitudinal HPV16 samples.

Human papillomavirus type 16 (HPV16) is the most common cause of cervical cancer, but most infections are transient with lesions not progressing to cancer. There is a lack of specific biomarkers for early cancer risk stratification. This study aimed to explore the intrahost HPV16 genomic variation in longitudinal samples from HPV16-infected women with different cervical lesion severity (normal, low-grade, and high-grade). The TaME-seq deep sequencing protocol was used to generate whole genome HPV16 sequences of 102 samples collected over time from 40 individuals. Single nucleotide variants (SNVs) and intrahost SNVs (iSNVs) were identified in the viral genomes. A majority of individuals had a unique set of SNVs and these SNVs were stable over time. Overall, the number of iSNVs and APOBEC3-induced iSNVs were significantly lower in high-grade relative to normal and low-grade samples. A significant increase in the number of APOBEC3-induced iSNVs over time was observed for normal samples when compared to high-grade. Our results indicates that the lower incidence of iSNVs and APOBEC3-induced iSNVs in high-grade lesions may have implications for novel biomarkers discoveries, potentially aiding early stratification of HPV-induced cervical precancerous lesions.

Sociodemographics, behaviour and knowledge of first South African HPV-vaccine recipients.

BACKGROUND:  Infection with the human papillomavirus (HPV) is a necessary cause of cervical cancer and is one of the most prevalent sexually transmitted infections worldwide. Primary prevention strategies target reducing HPV acquisition through vaccination, limiting exposure (e.g. delayed sexual debut, barrier contraception) and health education focusing on sexual behaviour and tobacco use. METHODS:  The ImmunoVACCS study, conducted from 2019 to 2022 in two provinces in South Africa, examined sociodemographic characteristics, sexual practices, and knowledge of cervical cancer and the HPV vaccine among young female vaccine recipients. It encompassed participants from the previously conducted vaccine implementation trials, VACCS 1 and VACCS 2 (2011-2014). Recruitment involved telephonic contact with eligible potential participants. Data were collected through self-administered questionnaires. RESULTS:  One hundred and eleven participants took part in the current study (median age: 20 years; age range: 16-22 years). Most sexually active participants had their first engagement in secondary school (96.2%), and 77.2% used contraception during their last sexual activity. Knowledge gaps were evident, with only 13.5% recognising cervical cancer's cervix origin and 3.6% attributing it to a virus. Despite this, 70.3% had heard of a vaccine for cervical cancer. Less than half knew about the importance of regular Pap smears (49.5%), vaccine protection (44.1%) or condom use (20.7%) against HPV and cervical cancer. CONCLUSION:  The current study demonstrates that young women still lack complete information on cervical cancer and its risk factors even after receiving health education linked with vaccination.Contribution: This study underscores the necessity of ongoing education about HPV, its risks and preventive measures among young women to combat cervical cancer.

[Research progress on the differences between T and B cell responses to three different forms of human papilloma virus (HPV) vaccination].

One of the most prevalent malignancies in women is cervical cancer. Cervical cancer is mostly brought on by chronic high-risk human papillomavirus 16 (HPV16) and HPV18 infection. Currently, the widely used HPV vaccines are the bivalent Cervarix, the tetravalent Gardasil, and the 9-valent Gardasil-9.There are differences in T cell effector molecule changes, B cell antibody level, duration, age and the injection after vaccination of the three vaccines.

Cervical cancer screening practices in HIV positive females - a missing link in health care delivery in Pakistan.

Objectives: To probe cervical cancer screening practices in local women positive for human immunodeficiency virus, and to determine the cervical cytological changes in them. METHODS: The serial cross-sectional study was conducted at the Jinnah Hospital and Services Hospital, Lahore, Pakistan, from April 2019 to October 2020, and comprised female patients aged 18-45 years who were positive for human immunodeficiency virus or acquired immunodeficiency syndrome and were registered with the relevant programme being run by the provincial government in Punjab. Blood samples of all the patients were collected for the determination of human immunodeficiency virus viral load and cluster of differentiation 4+ count. Cervical smears were taken for cytopathological analysis, while the swabs were analysed for culture sensitivity. The same individuals were subjected to the same testing one year later, and the status of the disease and clinical stability or disease progression was explored. Data was analysed using SPSS 25. RESULTS: There were 150 women with mean age 32.08±7.13 years (range: 21-45 years). Age at marriage/sexual activity was 17.33±4.73 years in 15(10%) subjects. Cytological examination showed atypical squamous cells of undetermined significance in 6(4%) of the cases whereas 3(2%) cases showed atypical squamous cells, which cannot rule out high grade squamous intraepithelial lesion on cytology, while the rest were classified as negative for intraepithelial lesion or malignancy. Cervical microbial changes revealed methicillin-resistant staphylococcus aureus infection in 9(6%) cases, extended-spectrum beta-lactamase in 15(10%) cases, whereas fungal infection and trichomonas vaginalis infection were found in 30(20%) smears. There was a significant association between cluster of differentiation 4+ cell count and stability of high-risk patients (p<0.001). After one year, 84(56%) patients remained clinically stable, while 51(34%) developed some chronic illness. There was a significant association between cluster of differentiation 4+ cell count <200/mm3 and the risk of developing a chronic illness (p<0.001). CONCLUSIONS: There was a dire need to educate healthcare workers to offer regular cervical screening to patients with high-risk sexually-transmitted infections to prevent them from the morbidity and mortality related to cervical cancer.

Distribution of HPV types among women with HPV-related diseases and exploration of lineages and variants of HPV 52 and 58 among HPV-infected patients in China: A systematic literature review.

To summarize the distribution of types of human papillomavirus (HPV) associated with HPV-related diseases and investigate the potential causes of high prevalence of HPV 52 and 58 by summarizing the prevalence of lineages, sub-lineages, and mutations among Chinese women. We searched PubMed, EMBASE, CNKI, and WanFang from January, 2012 to June, 2023 to identify all the eligible studies. We excluded patients who had received HPV vaccinations. Data were summarized in tables and cloud/rain maps. A total of 102 studies reporting HPV distribution and 15 studies reporting HPV52/HPV58 variants were extracted. Among Chinese women, the top five prevalent HPV types associated with cervical cancer (CC) were HPV16, 18, 58, 52, and 33. In patients with vaginal cancers and precancerous lesions, the most common HPV types were 16 and 52 followed by 58. For women with condyloma acuminatum (CA), the most common HPV types were 11 and 6. In Chinese women with HPV infection, lineage B was the most prominently identified for HPV52, and lineage A was the most common for HPV58. In addition to HPV types 16, which is prevalent worldwide, our findings revealed the unique high prevalence of HPV 52/58 among Chinese women with HPV-related diseases. HPV 52 variants were predominantly biased toward lineage B and sub-lineage B2, and HPV 58 variants were strongly biased toward lineage A and sub-lineage A1. Further investigations on the association between the high prevalent lineage and sub-lineage in HPV 52/58 and the risk of cancer risk are needed. Our findings underscore the importance of vaccination with the nine-valent HPV vaccine in China.

Effect of the HPV vaccination programme on incidence of cervical cancer and grade 3 cervical intraepithelial neoplasia by socioeconomic deprivation in England: population based observational study.

OBJECTIVES: To replicate previous analyses on the effectiveness of the English human papillomavirus (HPV) vaccination programme on incidence of cervical cancer and grade 3 cervical intraepithelial neoplasia (CIN3) using 12 additional months of follow-up, and to investigate effectiveness across levels of socioeconomic deprivation. DESIGN: Observational study. SETTING: England, UK. PARTICIPANTS: Women aged 20-64 years resident in England between January 2006 and June 2020 including 29 968 with a diagnosis of cervical cancer and 335 228 with a diagnosis of CIN3. In England, HPV vaccination was introduced nationally in 2008 and was offered routinely to girls aged 12-13 years, with catch-up campaigns during 2008-10 targeting older teenagers aged <19 years. MAIN OUTCOME MEASURES: Incidence of invasive cervical cancer and CIN3. RESULTS: In England, 29 968 women aged 20-64 years received a diagnosis of cervical cancer and 335 228 a diagnosis of CIN3 between 1 January 2006 and 30 June 2020. In the birth cohort of women offered vaccination routinely at age 12-13 years, adjusted age standardised incidence rates of cervical cancer and CIN3 in the additional 12 months of follow-up (1 July 2019 to 30 June 2020) were, respectively, 83.9% (95% confidence interval (CI) 63.8% to 92.8%) and 94.3% (92.6% to 95.7%) lower than in the reference cohort of women who were never offered HPV vaccination. By mid-2020, HPV vaccination had prevented an estimated 687 (95% CI 556 to 819) cervical cancers and 23 192 (22 163 to 24 220) CIN3s. The highest rates remained among women living in the most deprived areas, but the HPV vaccination programme had a large effect in all five levels of deprivation. In women offered catch-up vaccination, CIN3 rates decreased more in those from the least deprived areas than from the most deprived areas (reductions of 40.6% v 29.6% and 72.8% v 67.7% for women offered vaccination at age 16-18 and 14-16, respectively). The strong downward gradient in cervical cancer incidence from high to low deprivation in the reference unvaccinated group was no longer present among those offered the vaccine. CONCLUSIONS: The high effectiveness of the national HPV vaccination programme previously seen in England continued during the additional 12 months of follow-up. HPV vaccination was associated with a substantially reduced incidence of cervical cancer and CIN3 across all five deprivation groups, especially in women offered routine vaccination.

[Research progress of tumor-associated macrophages in cervical cancer].

Tumor-associated macrophages (TAM) can be differentiated into M1-type and M2-type macrophage phenotypes in the tumor microenvironment (TME), with M2-type macrophages playing a crucial role in malignant tumors. In cervical cancer, TAM exacerbates human papilloma virus (HPV) infection, promotes the proliferation, invasion, and metastasis of tumor cells, stimulates angiogenesis, and induces immune tolerance. TAM targeting strategies have emerged as a hot topic in cervical cancer immunotherapy.

Enhanced cervical cancer and HIV interventions reduce the disproportionate burden of cervical cancer cases among women living with HIV: A modeling analysis.

INTRODUCTION: Women living with HIV experience heightened risk of cervical cancer, and over 50% of cases in Southern Africa are attributed to HIV co-infection. Cervical cancer interventions tailored by HIV status delivered with HIV antiretroviral therapy (ART) for treatment can decrease cancer incidence, but impact on HIV-related disparities remains understudied. METHODS: Using a dynamic model calibrated to KwaZulu-Natal, South Africa, we projected HIV prevalence, cervical cancer incidence, and proportion of cancer cases among women living with HIV between 2021-2071. Relative to the status quo of moderate intervention coverage, we modeled three additive scenarios: 1) ART scale-up only; 2) expanded human papillomavirus (HPV) vaccination, screening, and treatment; and 3) catch-up HPV vaccination and enhanced screening for women living with HIV. RESULTS: Under the status quo, HIV prevalence among women aged 15+ decreased from a median of 35% [Uncertainty Range (UR): 26-42%] in 2021 to 25% [19-34%] in 2071. The proportion of cervical cancer cases that were women living with HIV declined from 73% [63-86%] to 58% [47-74%], but incidence remained 4.3-fold [3.3-5.7] that of women without HIV. ART scale-up reduced HIV prevalence in 2071, but increased the incidence rate ratio to 5.2 [3.7-7.3]. Disparities remained after expanding cancer interventions for all women (incidence rate ratio: 4.8 [3.6-7.6]), while additional catch-up HPV vaccination and screening for women living with HIV decreased the incidence rate ratio to 2.7 [1.9-3.4] in 2071. CONCLUSIONS: Tailored cervical cancer interventions for women living with HIV can counteract rising cancer incidence incurred by extended life expectancy on ART and reduce disparate cancer burden.

Human Papilloma Virus Infection and Gene Subtypes Analysis in Women Undergoing Physical Examinations: A 2015-2020 Study in Wenzhou, China.

BACKGROUND: Persistent infection with high-risk human papillomavirus (HPV) is closely related to cervical cancer. The epidemiologic characteristics of cervical HPV have regional differences. Therefore, it is necessary to develop the most favorable policies according to the actual situation of each region to prevent and reduce the prevalence of cervical cancer. This retrospective cross-sectional study investigated the prevalence, gene subtypes, and temporal trends of HPV in women undergoing physical examination in Wenzhou, to provide a decision-making basis for further prevention and control of HPV. METHODS: A total of 31 131 cervical exfoliated cell specimens obtained from physical examinations in Wenzhou, a coastal city of China, from 2015 to 2020 were collected. The age distribution was analyzed using the chi-squared test, and the time change trend was analyzed using the Mann-Kendall trend test. On this basis, the distribution characteristics of the HPV subtypes were analyzed. RESULTS: The total prevalence rate was 9.55%, and the prevalence rate in different age groups ranged from 7.77% to 14.16%. The prevalence rate in different years was 8.84%-11.83%. The prevalence rate was bimodal; it was highest in the group 25 years old, followed by the group >61 years old. The top five high-risk gene subtypes were HPV52, HPV58, HPV53, HPV16, and HPV39, whereas the low-risk subtypes were HPV61, HPV81, HPV44, HPV43, and HPV55. Of all the positive samples, 76.03% were infected with a high-risk subtype. CONCLUSION: Most female HPV patients in Wenzhou are infected with high-risk gene subtypes. Therefore, physical examination and screening for HPV should be further strengthened, and the corresponding vaccination policy should focus on high-risk gene subtypes.

BACKGROUND: Persistent infection with high-risk human papillomavirus (HPV) is closely related to the occurrence of cervical cancer. The epidemic characteristics of cervical HPV have regional differences, Therefore, it is necessary to formulate the most favorable policies according to the actual situation of each region, so as to prevent and reduce the prevalence of cervical cancer. This retrospective cross-sectional study investigated the prevalence, gene subtypes and temporal trends of HPV in women undergoing physical examination in Wenzhou. To provide decision-making basis for further prevention and control of HPV. METHODS: A total of 31,131 cervical exfoliated cell specimens obtained from physical examinations in Wenzhou, a coastal city of China from 2015 to 2020, were collected. The age distribution was analyzed by the chi-squared test, and the time change trend was analyzed by the Mann­Kendall trend test. On this basis, the distribution characteristics of HPV subtypes were analyzed. RESULTS: The total prevalence rate was 9.55%, and the prevalence rate in different age groups ranged from 7.77% to 14.16%. The prevalence rate in different years was 8.84%-11.83%. The prevalence rate was bimodal; it was highest in the group less than or equal to 25 years old, followed by the group greater than 61 years old. The top five high-risk gene subtypes were HPV52, HPV58, HPV53, HPV16 and HPV39, while for low-risk were HPV61, HPV81, HPV44, HPV43 and HPV55, respectively. Of all the positive samples, 76.03% were infected with a high-risk subtype.

Human papillomavirus and occupational exposure: The need for vaccine provision for healthcare providers.

To probe the understanding of healthcare providers regarding occupational exposure to human papillomavirus and their knowledge about human papillomavirus vaccination in relation to the American Society for Colposcopy and Cervical Pathology (ASCCP) recommendations. In this cross-sectional study, the healthcare providers at Mayo Clinic Arizona, Florida, and Minnesota were delivered an electronic survey. The survey was completed by 349 healthcare providers, with one respondent excluded for inconsistent entry. The mean age of respondents was 42.7 ± 10.9, and of those, 68% were female and 32% were male. Of the unvaccinated respondents, 43.3% were ≤ 45 y of age (eligible for vaccination), while those vaccinated formed 41% of the respondents. Healthcare providers are highly concerned about their cancer safety, as shown by their awareness of occupational human papillomavirus hazards and broad knowledge about vaccine efficacy. The use of personal protective equipment varied widely, including eyewear, double gloving, procedural face mask, N95 face mask, and/or nothing. Human papillomavirus and cancer risk was clearly perceived by healthcare providers. For professions, pairwise comparisons revealed that nurse practitioners, physician assistants, certified registered nurse anesthetists, and allied healthcare providers had lower scores than medical doctors. Despite the high level of understanding among healthcare providers of occupational human papillomavirus exposure, only a few of them knew of the recommendations of the ASCPP for vaccination of healthcare providers treating human papillomavirus-related diseases. In such cases, most of those surveyed embraced vaccination, which was considered 100% safe by medical doctors and allied health professionals.

Tobacco Smoke Condensate Induces Morphologic Changes in Human Papillomavirus-Positive Cervical Epithelial Cells Consistent with Epithelial to Mesenchymal Transition (EMT) with Activation of Receptor Tyrosine Kinases and Regulation of TGFB.

High-risk human papillomavirus (HR-HPV; HPV-16) and cigarette smoking are associated with cervical cancer (CC); however, the underlying mechanism(s) remain unclear. Additionally, the carcinogenic components of tobacco have been found in the cervical mucus of women smokers. Here, we determined the effects of cigarette smoke condensate (CSC; 3R4F) on human ectocervical cells (HPV-16 Ect/E6E7) exposed to CSC at various concentrations (10-6-100 µg/mL). We found CSC (10-3 or 10 µg/mL)-induced proliferation, enhanced migration, and histologic and electron microscopic changes consistent with EMT in ectocervical cells with a significant reduction in E-cadherin and an increase in the vimentin expression compared to controls at 72 h. There was increased phosphorylation of receptor tyrosine kinases (RTKs), including Eph receptors, FGFR, PDGFRA/B, and DDR2, with downstream Ras/MAPK/ERK1/2 activation and upregulation of common EMT-related genes, TGFB SNAI2, PDGFRB, and SMAD2. Our study demonstrated that CSC induces EMT in ectocervical cells with the upregulation of EMT-related genes, expression of protein biomarkers, and activation of RTKs that regulate TGFB expression, and other EMT-related genes. Understanding the molecular pathways and environmental factors that initiate EMT in ectocervical cells will help delineate molecular targets for intervention and define the role of EMT in the initiation and progression of cervical intraepithelial neoplasia and CC.