Human Papillomavirus Research Articles

The Role of Transoral Robotic Palatine and Lingual Tonsillectomy in the Diagnosis of Carcinoma of Unknown Primary in the Head and Neck Region.

The use of transoral robotic surgery (TORS) lingual tonsillectomy in the diagnostic algorithm for head and neck carcinoma of unknown primary (CUP) has gained recent popularity. The primary aim of our study was to determine the identification rate of primary tumors in our cohort undergoing lingual ± palatine tonsillectomy for the workup of head and neck CUP. This was a retrospective study of all patients undergoing diagnostic TORS for head and neck CUP over an eight-year period, across four centers in two countries. Fifty-six patients undergoing TORS to aid diagnosis of a primary site were included. Overall, TORS lingual ± palatine tonsillectomy identified a primary tumor in 41 (73.2%) patients. Over half were T1 tumors, with 25% measuring under 10 mm. Among those with human papilloma virus (HPV)+ nodal disease, the identification rate was 82.6%. TORS lingual tonsillectomy is an effective addition to the diagnostic workup of CUP, particularly in those with HPV+ nodal disease.

Excess Mortality in Persons with Concurrent HIV and Cancer Diagnoses: A Retrospective Cohort Study.

With extended lifespans for people with human immunodeficiency virus (PWH), there is a corresponding increased burden of chronic illnesses, including cancer. Our objective was to estimate the excess mortality for PWH with cancer compared with people without HIV (PWoH), accounting for the higher background mortality in the general PWH population. We identified 39,000 PWH and 387,767 demographically-matched PWoH in three integrated healthcare systems from 2000-2016. We estimated excess mortality for PWH with cancer, computed as the cancer mortality rate difference-in-difference comparing PWH and PWoH. We evaluated five cancer groups: any cancer; virus-, human papillomavirus-, and Epstein-Barr virus (EBV)-related cancers; virus-unrelated cancers, and common individual cancers. We fitted a multivariable additive Poisson model to estimate excess mortality for PWH with cancer. PWH with any cancer had excess mortality compared with PWoH (41.3/1000 person-years [py], 95% Confidence Interval [CI] 34.0, 48.7). The highest excess mortality was observed for EBV-related cancers (63.2/1000 py, 95% CI 47.8, 78.7), lung cancer (147.7/1000 py, 95% CI 41.1, 254.3) and non-Hodgkin lymphoma (70.5/1000 py, 95% CI 51.4, 89.6). Excess mortality for PWH was attenuated 2009-2016, and PWH with cancer had no excess mortality 5 years after diagnosis. PWH in care may have excess mortality from certain cancer types, although disparities may have attenuated over time and do not persist beyond 5 years after diagnosis. Findings may guide improved clinical practice, and suggest further research is needed to investigate whether cancer treatment or other factors contribute to mortality disparities for PWH with cancer.

Age-specific 3-year risk of cervical precancer among HPV-positive women attending screening: a post hoc analysis from a retrospective cohort

This post hoc analysis explored the age-specific risk of cervical precancer in women infected with human papillomavirus (HPV), using data from a cohort of 7263 participants aged 21-71years undergoing cervical screening. We found a slightly varied prevalence of high-risk HPV (hrHPV) in different age, with highest in women under 30 years old (9.28% for 13 hrHPVs tested by HC2-HPV, 10.82% for 14 hrHPVs tested by DH3-HPV). However, the prevalence of cytology abnormalities peaked in age 30–39 years (~ 3.6%). A total of 5840 women completed 3-year follow-up. Among them, 558 were positive for HC2 assay and 583 were positive for DH3-HPV at baseline. Of note, the 3-year cumulative risks for cervical intraepithelial neoplasia grade 2+ (CIN2+) or grade 3+ (CIN3+) in women infected with high-risk HPV did not increase with age but declined (e.g., 41.67%, 27.78%, 26.42%, 15.98%, and 18% for CIN2 + risk in HC2-positive women at year 25–29, year 30–39, year 40–49, year 50–59, and year 60–71, respectively). If stratified by the median age, younger women (25–48 years) positive with HC2-HPV at baseline had a higher 3-year CIN2+/CIN3 + risk than older women (49–71 years) [26.55% (95%CI = 21.8-31.92%) vs. 18.28% (95%CI = 14.11-23.34%), P = 0.019; 15.52% (95%CI = 11.81-20.14%) vs. 9.7% (95%CI = 6.71-13.83%), P = 0.039]. Similarly, for women positive with DH3-HPV at baseline, younger group had a higher 3-year CIN2+/CIN3 + risk than older group [26.44% (95%CI = 21.73-31.75%) vs. 17.01% (95%CI = 13.11-21.78%), P = 0.006; 15.25% (95%CI = 11.6-19.8%) vs. 9.03% (95%CI = 6.24-12.9%), P = 0.021]. These findings indicate the potential value of age-specific risk assessment in cervical cancer screening.

Expanding the clinical utility of liquid biopsy by using liquid transcriptome and artificial intelligence

Most of the current utilization of liquid biopsy (LBx) is based on analyzing cell-free DNA(cfDNA). There is limited data on using cell-free RNA (cfRNA) levels (liquid transcriptome) in LBx. The major hurdles for using liquid transcriptome is its low level in circulation and the dilutional effects of various tissues that may pour their RNA into circulation. We explored the potential of using artificial intelligence (AI) to normalize the cancer-specific cfRNA and to enable liquid transcriptome to predict diagnosis. cfRNA transcriptomic data from 1009 peripheral blood samples was generated by hybrid capture next generation sequencing (NGS). Using two-thirds of samples for training and one third for testing, we demonstrate that AI is able to distinguish between normal control (N = 368) and patients with solid tumors (N = 404) with AUC = 0.820 (95 % CI: 0.760–0.879), patients with myeloid neoplasms (N = 99) with AUC = 0.858 (95 % CI: 0.793–0.924) and patients with lymphoid neoplasms (N = 128) with AUC = 0.788 (95 % CI: 0.687–0.888). Specific diagnosis was also possible when patients with lung, breast, colorectal, and myelodysplastic subgroups were tested. This data suggests that liquid transcriptomics when used with AI has the potential of transforming “liquid biopsy” to “true” biopsy, replacing the need for tissue biopsy.

Multitargeted docking approach reveals droxidopa against DNA replication and repair-related protein of cervical cancer

Cervical cancer begins in the cells lining the cervix and is caused by persistent infection with certain types of human papillomavirus (HPV). Initially, it has no symptoms, and later it causes pelvic pain, abnormal vaginal bleeding, and pain during intercourse. It is the fourth-ranked cancer among women, and many women die from cervical cancer every year, particularly in low-income countries and the majority could be prevented with early detection and treatment. In this study, we have taken Cervical Cancer DNA Replication and Repair-Related Protein with the PDBID- 3H15, 5VBN, and 6NT9 and performed the multitargeted molecular docking with the FDA-approved drug library using HTVS, SP and XP docking. Then, the poses were filtered with MM\\GBSA for proper computations of free energy, identified a multitargeted inhibitor Droxidopa with docking and MM\\GBSA scores ranging from − 5.559 to − 6.835 Kcal/mol and − 26.04 to − 37.33 Kcal/mol, respectively. We also performed interaction fingerprints revealing 2VAL, 2LYS, 1ALA, 1ARG, 1ASN, 1CYS, 1GLN, 1GLU, 1ILE, 1MET, 1PHE, 1PRO, 1SER, and 1THR were most interacted residues and computed the ADMET properties with QikProp and DFT with Jaguar, which supported the study and compounds’ suitability. Moreover, we performed the 100ns MD simulation in water, showing the controlled deviation and fluctuations of the residues with many interactions, and MM\\GBSA was performed with the same trajectories, showing a better understanding of each frame’s total complex and binding-free energy. The whole study favours droxidopa as an inhibitor of cervical cancer DNA Replication and Repair-Related Proteins—however, experimental studies are needed before use.

Recent advances in HPV biotechnology: Understanding host-virus interactions and cancer progression-a review

Cervical cancer ranks as the fourth most common cancer among women globally, posing a significant mortality risk. Persistent infection with high-risk human papillomavirus (HPV) is the primary instigator of cervical cancer development, often alongside co-infection with other viruses, precipitating various malignancies. This study aimed to explore recent biotechnological advances in understanding HPV infection dynamics, host interactions, and its role in oncogenesis. The gathered data shed light on HPV biology, host-virus interplay, viral co-infections, and cellular transformations leading to HPV-associated cancers. Recent years have seen the introduction of diverse vaccination strategies, including live attenuated, subunit, and DNA-based vaccines, complemented by innovative nanotechnology and plant-based products. Despite rich data addressing research inquiries, urgent calls echo for the implementation of contemporary screening and therapeutic modalities at clinical levels. Moreover, extensive public awareness campaigns are imperative to alleviate the burden of HPV-related diseases, emphasizing the necessity for proactive intervention strategies in combating this global health challenge.

Analysis of factors affecting the accuracy of colposcopic diagnosis of cervical lesions: a retrospective cohort study.

Cervical cancer is a leading cause of cancer-related deaths among women. However, in developing countries, the primary focus for cervical cancer prevention and control remains on the timely detection and treatment of precancerous lesions. This study aims to evaluate the accuracy of colposcopic diagnosis of cervical intraepithelial lesions and analyze the factors influencing its accuracy. This study collected data from 512 eligible patients who visited the gynecology outpatient clinic of the Second Hospital of Jilin University from January 2022 to August 2023. The final diagnosis was based on the highest grade observed in both biopsy pathology and postoperative pathology. A self-controlled, retrospective analysis was conducted to evaluate the accuracy of colposcopic diagnosis. Univariate analysis was used to assess the impact of factors such as menopausal status, duration of menopause, high-risk human papillomavirus (HR-HPV) genotypes, and transformation zone (TZ) types on the accuracy of colposcopic diagnosis of cervical lesions. The overall colposcopy diagnostic concordance rate was 78.71%. The concordance rates between the premenopausal and postmenopausal groups differed significantly (χ 2 = 75.450, p < 0.05). The HPV16/18 positive group and the non 16/18 HR-HPV positive group also showed a significant difference in concordance rates (χ 2 = 5.890, p < 0.05). There were significant differences in concordance rates between TZ2 and TZ3 (χ 2 = 10.585, p < 0.05), as well as between TZ1 and TZ3 (χ 2 = 14.607, p < 0.05). Factors such as menopausal status, duration of menopause, HR-HPV genotypes, and TZ types influence the accuracy of colposcopic diagnosis. Therefore, a comprehensive evaluation incorporating these factors should be performed in clinical practice to enhance diagnostic accuracy.

HPV-Independent Cervical Adenocarcinoma Discovered by Cytology-Based Screening: A case report of gastric type adenocarcinoma of the uterine cervix from cytopathology to histopathology

Abstract Introduction/Objective In recent years, the relative prevalence of adenocarcinoma has increased, comprising 20–25% of all cervical carcinomas in developed countries. Approximately 15% of cervical adenocarcinomas are unrelated to human papilloma virus (HPV) infection. With the shift toward HPV primary testing, an increased understanding of HPV-independent cervical adenocarcinomas becomes more important. Methods/Case Report This case report demonstrates a rare case of gastric-type adenocarcinoma (GAS) of the cervix discovered during a routine well-woman exam. Patient-reported episodes of vaginal spotting were noted prior to screening. HPV testing by PCR on the initial pap smear was negative. Cytology findings raised concerns about endocervical glandular cell abnormalities. Subsequent cervical biopsy revealed GAS, a finding supported by positive CK7, MUC5AC, CDX2, and aberrant (mutant) p53 expression by immunohistochemistry. HPV independence was further confirmed by negative results on mRNA ISH for high-risk HPV and HPV16/18. Results (if a Case Study enter NA) NA Conclusion Here we discuss the impact of cytology-based screening on HPV-independent cervical cancers, with focus on adenocarcinoma. While the move to primary HPV screening has been shown to be effective at identifying HPV-related neoplasms, it ineffectively addresses HPV-independent malignancies. In this particular population, cytology-based screening remains indispensable. The described case demonstrated subtle cytologic features consistent with endocervical glandular abnormality, ultimately correlating with subsequent histologic findings of HPV-independent GAS. Negative HPV results combined with subtle cytomorphologic changes displayed by some adenocarcinomas on PAP smear could present a significant diagnostic pitfall. Additionally, p16+ expression attributable to aberrant p53 pathways (rather than HPV) may further contribute to potential diagnostic errors. While further research into best practices for early detection of HPV-independent cervical neoplasias should be conducted, this team suggests both clinical survey and referral for cytologic screening following reports of abnormal vaginal bleeding and/or watery discharge and screener education focused on cervical GAS.

Long-term outcomes of high-risk human papillomavirus in anal infection support HPV men vaccination

Abstract Introduction/Objective The clinical laboratory in a local hospital has an important role in population surveillance. The clinical laboratory performs analyses on patients admitted to the hospital as inpatients or critical patients and it is also a reference point for people’s health check-ups and health surveillance. Infectious diseases normally have severe symptoms. To ensure benefits from therapeutic treatment, a timely diagnosis is necessary. The human papillomavirus (HPV) virus is among the most diagnosed sexually transmitted infections worldwide, and the male gender is not exempt from it. In fact, 1 out of 3 male individuals is infected with HPV and 1 out of 5 male individuals is infected with a high-risk strain (1). In Italy, vaccination is underway for women only. Vaccine prevention extended to male individuals could lead to a halving of HPV cases. Methods/Case Report From 2018 to 2022, we performed 7362 HPV tests using DNA extraction technique (QiaSimphony) and real-time Multiplex PCR (SeeGene 28 strains). Results (if a Case Study enter NA) 3762 out of 7362 HPV tests performed were positive for one (2059 patients) or more (1969 patients) HPV strains. Women, who are more aware of prevention, are more represented in our sample of subjects. The tests performed on women are 6499 and half (3331) are positive for at least one strain of HPV. Regarding men, 863 tests were performed. About half (431 patients) were positive for at least one HPV strain. Noteworthy, out of 175 anal HPV tests, 48% were positive and 1 patient had squamous cell carcinoma. Furthermore, in our male patients tested 2 - 12% had low or medium-risk injuries. In total, out of 7529 tests carried out from 2018 to 2022, over than 50% were found to be high-risk viral strains (5231). Of these, however, approximately half (2781) are now preventable with the monovalent HPV vaccine (strains covered: 6, 11, 16, 18, 31, 33, 45, 52, 58). Conclusion The Ospedale Isola Tiberina – Gemelli Isola is an Institution in the center of Rome, Italy. It is also a reference center for birthrates and women’s prevention. Therefore, our Institution is very efficient in raising awareness of the prevention of HPV-related cancer. Current data indicate that male cases are not negligible, being positive in almost 50% of anal tests, and associated with an increased risk of the related cancers. These data can have an important impact on the Italian population, both in terms of the spread of HPV and healthcare burden and in terms of high healthcare costs.

Evaluation of Automatic Signal Detection of In Situ Hybridization for Detecting HPV DNA in Cervical Tissue Derived from Patients with Cervical Intraepithelial Neoplasia

Background: Cervical cancer is fourth the most common cancer in women worldwide. Due to the prevalence of human papillomavirus (HPV) in the population (80–90%), scientists are likely to discover even more associations of this pathogen with other diseases in the future. In recent years, In Situ Hybridization (ISH) assays that use automated signal-detecting methods in formalin-fixed, paraffin-embedded (FFPE) cervical tissue, such as the enzyme-categorized signal-detecting system, have shown a higher sensitivity. Objectives and Methods: To evaluate automatic signal detection of ISH assay for detecting HPV DNA, we compared the ability of an ISH probe, Inform HPV II and III (Ventana Medical Systems, Tucson, AZ), to that of PCR assays to detect HPV DNA in cervical tissue specimens with cervical intraepithelial neoplasia (CIN; CIN 1, 28 cases; CIN 2, 22 cases; and CIN 3, 20 cases) and normal cervix (2 cases). Results: Our findings showed a significant relation was confirmed between ISH III level and HPV outcome (positive/negative). Patients with positive HPV outcomes had significantly lower ISH III levels, MD = −7961.82 CI95 [−17,230.00; −199.21], p = 0.005. Conclusions: Automatic signal detection of ISH assay is not particularly applicable to cervical tissue material. A more useful method of confirming the presence of HPV in the cervix is the HPV test with genotyping, as it allows for collecting a larger amount of material from the cervical disc and canal. The interpretation of a positive or negative ISH test must be guided in the context of clinical history and morphology.

A Quality Improvement Study for Cervical Cancer Screening: Estimating the use of cotesting versus Reflex HPV testing at the time of screening

Abstract Introduction/Objective The recommendations for cervical cancer screening have changed over the years. One of the major changes include inclusion of HPV testing in the screening protocols. A brief scan of our lab data indicated that during the period of Jan-Oct 2023, a small group of women over the age of 30 have not been co-tested. While cytology alone is acceptable, it is less sensitive than other recommended screening options. Therefore, the quality of care these women receive is acceptable but not preferred. We aim to quantify those cases, find reasons why HPV testing was not ordered, and estimate the usage of reflex HPV testing. Methods/Case Report A retrospective analysis was performed of patients screened for cervical cancer with pap testing over 10 months (Jan - Oct 2023) at Geisinger Medical Laboratories. Out of 32849 patients screened for cervical cancer, we identified 546 cases without HPV testing. A chart review of the cases was performed, followed by sending a survey to the respective providers to find out when they prefer reflex HPV testing over cotesting. Results (if a Case Study enter NA) Data analysis showed that 546 out of 32849 cases were screened without co- testing by 102 providers. These providers checked the “HPV if ASCUS” option in the HPV permission section of the cytology requisition form. These cases were diagnosed as Negative for Intraepithelial Lesion on a pap test. We sent a survey to the providers, and responses showed that the reflex HPV testing option is used for patients younger than 30 years by 90% of the providers. Only 10% of providers use cytology alone due to cost issues for patients over 30. Most providers (60%) do not want the reflex testing option to be removed from the HVP permission section. Conclusion The majority of the women above 30 years of age are screened for cervical cancer with co-testing, but a small group (1.6%) is tested with cytology alone mainly due to cost-benefit hence compromising on the sensitivity of the screening test. We recommend the following changes to our cytology requisition form. If the provider selects HPV Reflex testing, the HPV test should be performed in the following scenarios: a) The pap test’s final diagnosis is NIL, and the patient is between ages 30-64. b) The pap test’s final diagnosis is ASCUS, and the patient is between ages 21 and 64. c) The pap test’s final diagnosis is LSIL; the patient is non-pregnant and between ages 25 and 64. Modifying the HPV Reflex option will improve the quality of our patient care and align our practices with current recommendations.

Human Papillomavirus (HPV) Vaccination Rates Among U.S. Military Veteran Females and Males and Non-Veterans in the National Health Interview Survey.

Human papillomavirus (HPV) infection is a major risk factor for the development of multiple cancers. Active duty service members have higher rates of HPV infection than civilians, while Veterans are diagnosed with a disproportionately high burden of HPV-associated cancers compared to civilians without prior service. While a highly effective HPV vaccine has been available for over a decade, vaccination rates in the United States remain suboptimal. The objective of this study was to investigate HPV vaccination rates among male and female Veterans compared with their non-Veteran counterparts. We performed a secondary analysis of cross-sectional National Health Interview Survey (NHIS) data pooled from 2015 to 2018 to analyze HPV vaccination rates for respondents aged 18-45 years. We used multivariable logistic regression to compare HPV vaccination rates between Veterans and non-Veterans stratified by sex while controlling for sociodemographic factors, including age, race/ethnicity, education level, income, insurance coverage, and VA coverage. All analyses used NHIS survey weights to produce national estimates. Among 45,493 respondents aged 18 to 45 years, vaccination rates were low across all groups: 9.6% of male Veterans and 8.4% of male non-Veterans (P = .21) had received at least one HPV immunization, whereas 32.0% of female Veterans and 25.1% of female non-Veterans (P = .02) were immunized. After controlling for sociodemographics, both male Veterans (AOR 1.79; 95%CI 1.31, 2.44) and female Veterans (AOR 1.56; 95%CI 1.1, 2.21) exhibited higher odds of HPV vaccination compared to their non-Veteran counterparts. VA coverage was also independently associated with higher odds of HPV vaccination among female Veterans (AOR 2.39; 95%CI 1.10, 5.21). Veterans of both sexes are more likely to be vaccinated than their non-Veteran civilian counterparts. However, vaccination rates overall remain low. To our knowledge, ours is the first study of its kind to establish HPV vaccination rates among female Veterans. These findings underscore the important role of DoD and VA health care systems in improving HPV vaccine uptake and mitigating HPV-associated cancer risk among Veterans.

High-risk human papillomavirus diversity among indigenous women of western Botswana with normal cervical cytology and dysplasia

BackgroundCervical cancer remains a public health problem despite heavy global investment in health systems especially in low-and-middle-income countries (LMIC). Prophylactic vaccines against the most commonly detected human papillomavirus (HPV) types in cervical cancers are available and decisions on the selection of vaccine design depends on the prevalence of high-risk (hr) HPV genotypes for a particular region. In 2015, Botswana adopted the use of a quadrivalent HPV vaccine as a primary prevention strategy. Secondary prevention includes cervical smear screening whose uptake remains notably low among indigenous and marginalized communities despite efforts to improve access.AimTo determine the prevalence of hrHPV genotypes and cervical lesions’ burden in women from the indigenous and marginalized communities of Botswana.MethodsThis prospective survey enrolled 171 non-HPV vaccinated women aged 21 years and older. Face-to-face interviews, Pap smear screening, hr-HPV and Human Immuno-deficiency virus (HIV) testing were carried out. Conventional Papanicolau smears were analyzed and cervical brushes were preserved for hrHPV testing using the Ampfire Multiplex HR-HPV protocol which detects the following genotypes: HPV 16, 18, 31, 35, 39, 45, 51, 52, 53, 56, 58, 59 and 68.ResultsIn this study, 168/171 (98.6%) of the women consented to HIV testing; 53/171 (31%) were living with HIV and self-reported enrolment on antiretroviral therapy. Among the women examined, 23/171 (13.5%) had cervical dysplasia with most presenting with Atypical Squamous Cells of Undetermined Significance 8/23 (35%), Low-Grade Squamous Intraepithelial Lesions 8/23 (35%), Atypical Squamous Cells-High Grade 4/23 (17%), Atypical Endocervical Cells 2/23 (9%) and Atypical Endocervical Cell favoring neoplasia 1/23(4%). However, no High-Grade Squamous Intraepithelial Lesions (HSIL) or squamous cell carcinoma (SCC) were detected. Overall hrHPV prevalence in this study was at 56/171 (32.7%). The most commonly detected hrHPV genotypes in women with cervical dysplasia were HPV39 (6.25%), HPV51 (14.5%), HPV52 (12.5%) and HPV56 (4%). Notably, HPV 16 and 18 were not found in women with cervical dysplasia.ConclusionsOur study provides valuable insights into the prevalence and distribution of hrHPV genotypes in indigenous and marginalized communities in Botswana, and the need for further investigation of their potential role in cervical carcinogenesis in this population. These results may also serve as baseline data to facilitate future evaluation of the HPV vaccine needs.

Utility of The Paris System for Reporting Urinary Cytology in patients with HPV-positive urinary tract carcinoma.

Human papillomavirus (HPV)-positive urinary tract carcinomas (UTCas) have distinct morphology and molecular features with potential treatment implications. Cytomorphologic analysis of these tumors on urine cytology specimens has not yet been reported. The authors evaluated the cytomorphologic findings of HPV-positive UTCa on urine cytology using The Paris System for Reporting Urinary Cytology (TPS) criteria. HPV-positive cases were identified by a retrospective review of surgical specimens that had UTCa confirmed by HPV in situ hybridization. Cases that had concurrent urine cytology were reviewed using TPS. Cytomorphologic features of high-grade urothelial carcinoma (HGUC) were evaluated as well as the presence of atypical squamous cells (ASCs) and basaloid features. Sixteen cytology specimens from eight patients with HPV-positive UTCa were included. On original diagnosis, none of the cytology specimens were suggested to be HPV-associated. TPS diagnostic criteria identified eight cases with at least atypical findings, including five HGUC cases, one case that was suspicious for HGUC, and two atypical urothelial cases. Common cytomorphologic features included basaloid clusters (six of eight cases; 75%) and ASCs (four of eight cases; 50%) that matched the corresponding surgical specimens. Most cases exhibited urothelial cell hyperchromasia (seven of eight cases; 88%), and hypochromasia was a frequently observed variant (four of eight cases; 50%), either alone or in addition to hyperchromasia. HPV-positive UTCa can be identified reliably as HGUC by using TPS criteria; however, these cases may not be recognized as HPV-associated. The presence of basaloid cells or ASCs can help suggest screening for HPV in urine specimens. Larger scale studies are warranted to validate cytomorphologic differences and determine the impact of HPV infection on clinical outcomes for patients with UTCa.

Prevalence and distribution of human papillomavirus genotypes in women with abnormal cervical cytology in Ethiopia: a systematic review and meta-analysis.

Cervical cancer is the 4th most common cancer in women globally. Determining the prevalence of the high-risk human papillomavirus (HR-HPV) and low-risk (LR-HPV) genotypes and the distribution in abnormal cervical cytology will be essential in a future population-based cervical cancer prevention program. Primary studies with women with abnormal cervical cytology were systematically searched for in Medline, CINHAL, Google Scholar, African Journal Online, and the University of Antwerp repository from 19-30 May 2023. A weighted inverse-variance random effects model was used. Variations across the studies were checked using a forest plot, I2 statistics, and Egger's test. Group analysis was performed for evidence of heterogeneity. The pooled prevalence of human papillomavirus (HPV) genotypes with abnormal cervical cytology of a precancerous cervical lesion was 38.74% (95% CI: 27.56-49.93). The leading pooled prevalence estimates by subgroup analysis were 18% (95% CI: 13-26), 14% (95% CI: 111-16), and 66% (51-79) for women with retroviral infection (RVI), DNA genotyping with amplification, and central parts of Ethiopia respectively. There were 25 HPV variants identified by genotyping techniques with the five most prevalent HPV genotypes being HPV-16 and HPV-18 coexisting at 54%; HPV-16 alone at 29%; HPV-51 at 16%; HPV-52 at 13%; and HPV-31 and HPV-33 each contributing approximately 12%. The pooled prevalence of HPV genotypes was higher than in other countries. HPV-51, HPV-52, HPV-31, and HPV-33 are the most prevalent genotypes. Hence, the nonavalent vaccine type would be the one that includes all the most prevalent HPV genotypes, but HPV-51in Ethiopia. Additional data on similar DNA test techniques for comparisons with precancerous lesions and invasive cancer are needed. Cervical cancer prevention and control programs in Ethiopia should be aligned with the most prevalent genotypes. https://www.crd.york.ac.uk/prospero/, identifier CRD42023428955.

RPA-CRISPR-Cas-Mediated Dual Lateral Flow Assay for the Point-of-Care Testing of HPV16 and HPV18.

The incidence of cervical cancer caused by human papillomavirus (HPV) infection has increased in recent years. More than half of all cervical cancer cases are due to HPV16 and HPV18 infection, so HPV16 and HPV18 testing is essential to prevent cervical cancer. HPV testing is mainly carried out in hospitals, but it is subject to time and specialized medical facilities. On the other hand, home self-testing using simple diagnostics would present an attractive alternative due to privacy and flexibility with regard to time and place, provided sufficient sensitivity and specificity can be achieved. In this work, a dual lateral flow assay based on RPA-CRISPR-Cas12a/13a (named RC-LFA) for HPV detection was described. Taking advantage of the cleavage specificity of Cas12a and Cas13a, a CRISPR-Cas12a/Cas13a system was designed to detect HPV16 and HPV18. The lateral flow strip with two test lines was designed to suit the CRISPR-Cas12a/Cas13 system. RC-LFA achieves rapid and simultaneous detection of HPV16 and HPV18 with high specificity and sensitivity (10 copies/μL) in about 40 min from the extraction of nucleic acid to an instrument-free readout. RC-LFA is user-friendly and instrument-free, making it a promising method for HPV self-tests at home.

Advanced Human Papillomavirus–Negative Head and Neck Squamous Cell Carcinoma: Unmet Need and Emerging Therapies

Abstract Despite notable progress in the treatment of advanced head and neck squamous cell carcinoma (HNSCC), survival remains poor in patients with recurrent and/or metastatic (R/M) human papillomavirus (HPV)–negative HNSCC. Worse outcomes in patients who are HPV-negative may be partly related to loss of cell-cycle regulators and tumor suppressors as well as a noninflamed and hypoxic tumor microenvironment, both of which contribute to treatment resistance and disease progression. Anti–programmed cell death protein 1–based regimens as current standard-of-care treatment for R/M HNSCC are associated with durable responses in a limited number of patients. The anti-EGFR mAb, cetuximab, has antitumor activity in this treatment setting, but responses are short-lived and inevitably curtailed due to treatment resistance. Crosstalk between the EGFR and hepatocyte growth factor–dependent mesenchymal–epithelial transition (c-MET) receptor tyrosine kinase pathway is a known mechanism of resistance to cetuximab. Dual targeting of EGFR and c-MET pathways may overcome resistance to cetuximab in patients with HPV-negative HNSCC. Here, we review clinical data of treatments evaluated in patients with R/M HPV-negative HNSCC and highlight the potential role of combining hepatocyte growth factor/c-MET and EGFR pathway inhibitors to overcome cetuximab resistance in this population.

Pediatric non-nasopharyngeal head and neck squamous cell carcinoma: Analysis of the Surveillance, Epidemiology, and End Results (SEER) program with review of the literature

BackgroundDespite its prevalence in adults, head and neck squamous cell carcinoma (HNSCC) is considered a rare entity in pediatrics where lymphomas, neural tumors, and soft tissue sarcomas predominate in the head and neck. Given the association of squamous cell carcinoma with the human papillomavirus, a risk factor that may be present from birth, and the difficulties in staging this disease for prognostication in children, it is important to revisit nationally collected data for prevalence and outcomes assessments. ObjectiveTo examine a publicly available national database to describe the incidence, pathology, treatment, and survival of pediatric HNSCC. To review the available literature regarding management, outcomes, and risk factors for this disease process. MethodsThe National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) tumor database was queried to identify pediatric subjects ages 0 to 19 diagnosed HNSCC between 1973 and 2019. ResultsTwo-hundred ninety-two cases were identified. Subjects were 62.7 % male (n = 183) and the average age was 15.4 years (range 2–19, median 16). Subjects were 65.8 % white (n = 192), 22.9 % black (n = 67), 8.9 % Asian/Pacific Islander (n = 26), 1 % American Indian (n = 3), and 1.4 % unknown (n = 4). The most common primary sites were nasopharynx (45.9 %), oral cavity (30.5 %), larynx (8.6 %), salivary gland (4.1 %), nasal cavity & paranasal sinus (3.4 %), and lip (2.7 %). There was no statistically significant difference between primary subsite and age, race, histologic grade, or extent of disease. The 5-year overall survival was 83.6 %. DiscussionHead and neck squamous cell carcinoma is more likely to present in older children and is more prevalent in White populations. The nasopharynx is the most common subsite involved, which differs from adult populations in which non-nasopharyngeal subsites including the larynx, oral cavity, and oropharynx are most frequently affected. ConclusionHead and neck squamous cell carcinoma is rare in pediatric patients but should not be overlooked by physicians in the differential diagnosis, particularly in teenagers. Further study is needed to determine whether this represents a unique entity or can be staged and treated according to adult guidelines.

HPV Vaccination Stages and Associated Factors Among Children of Immigrant Women.

This study aimed to identify key determinants by stage of implementation of human papillomavirus (HPV) vaccination among children of immigrant women in South Korea. Cross-sectional descriptive study. The sample comprised 262 Chinese, Vietnamese, and Korean-Chinese women with children living in South Korea. The survey was conducted using self-report questionnaires. The HPV vaccination levels in children were classified into four transition stages. Sequential logistic regression analysis was conducted to identify the factors affecting the transition of HPV vaccination status. Social norms had the greatest influence on the intention to vaccinate. Perceived barriers were a significant factor associated with intention or initiation of vaccination, whereas perceived severity and susceptibility were associated with the intention and initiation stages, respectively. Upon the initiation of HPV vaccination, low perception of discrimination in healthcare was associated with continued vaccination. Given the importance of completing multiple doses of the HPV vaccine within a given timeframe, it is important to provide culturally appropriate interventions in stages to prevent dropouts.

The role of co-infections on cervical intraepithelial neoplasia prevalence in western Kenya.

Background Screening for co-infections with HIV, HSV-2 and Chlamydia trachomatis (CT ) among high-risk human papilloma virus (hr-HPV) positive women remains essential in alleviating high morbidity of cervical cancer (CC). The aim of this study was to determine the prevalence of cervical intraepithelial neoplasia (CIN) among women referred for CC screening at a referral hospital in Kisumu County, Kenya; and to establish the role of co-infection on CIN. Method In a cross-sectional study, we collected HPV, HIV, HSV-2 and CT data, cervical cytology results, and demographic information from 517 referrals. Blood samples were obtained for HIV and HSV-2 tests; urine for CT test and cervical swabs for hr-HPV test. Results The overall prevalence of CIN was 18.4% (95/517) with CIN1 observed in 56(29.6%), CIN2 in 27(`14.3%), CIN3 + in 12(6.3%) and normal biopsy in 94(49.7%) of the patients out of which high grade CIN2 and above (CIN2+) was 7.54% (39/517) equivalent to 32.5 per 100,000 women per year. HPV/HIV co-infection (infected vs. uninfected: OR 2.79; 95% CI 1.56-5.10, p < 0.001); HPV/HSV-2 co-infection (infected vs. uninfected: OR 2.41, 95% CI: 1.12-5.46, p < 0.024); HPV/CT co-infection (infected vs. uninfected: OR 3.83; 95% CI 1.84-8.51, p < 0.001) were found to be significantly associated with CIN. Conclusion Overall prevalence of CIN was high in the region although high-grade CIN2 + remained relatively lower as reported earlier. Age factor, widowhood and co-infections with HIV, HSV-2 or Chlamydia trachomatis were associated with increased risk of testing positive for CIN.