Papillomavirus Infection Research Articles

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.

Concomitant Cervical and Anal Screening for Human Papillomavirus (HPV) – Worth the effort or waste of time?

Abstract Background Human papilloma virus (HPV) infection represents the most common sexually transmitted disease and a major risk factor for disease progression to anal cancer. Aims This study aimed to analyze the rate of concomitant anal dysplasia in a prospectively surveilled cohort of sexually active women. Methods This study represents a follow-up analysis of the AnusGynecology (ANGY) study (doi.org/10.3390/cancers14205096). This prospective, cross-sectional single-center study recruited women for concomitant cervical and anal screening of HPV genotypes and cytology during a single appointment. Cervical / anal smears +/- biopsies if deemed necessary were performed by board-certified specialists during a single outpatient visit. All women with findings of either HPV or any type of dysplastic lesions on anal smears were offered follow-up in a specialized high-resolution anoscopy (HRA) outpatient clinic. Results Overall, 275 patients (mean age 42±12) were included. Among them, 102 (37%) had cervical high risk (HR)-HPV. Anal smear cytology was performed in 255 patients (93%), while 19 patients (7%) underwent anal biopsy during the combined visit. In total, HPV was (incidentally) revealed in 91 patients (33%) on anal smears, while any degree of anal dysplasia was found in 30 patients (11%), 6 if which were high-grade squamous intraepithelial lesions (H-SIL). Furthermore, 10 out of 19 biopsies were positive (3 H-SIL lesions). Only half (48/93, 52%) of women agreed to undergo the recommended specialized follow-up evaluation. Of them, 18 (38%) were diagnosed with dysplastic lesions (9 L-SIL and H-SIL, respectively) on biopsies, while the remaining visits revealed no abnormalities. Conclusion The present study revealed a significant number of dysplastic lesions in women willing to undergo specialized proctologic evaluation after abnormal findings on initial screening. Close follow-up of these women is hence strongly recommended.

Human papillomavirus infection and the risk of cancer at specific sites other than anogenital tract and oropharyngeal region: an umbrella review

Despite numerous studies having evaluated the associations between human papillomavirus (HPV) infection and risk of specific cancers other than anogenital tract and oropharyngeal, the findings are inconsistent and the quality of evidence has not been systematically quantified. We aimed to summarise the existing evidence as well as to evaluate the strength and credibility of these associations. We conducted an umbrella review of systematic reviews and meta-analyses of observational studies. PubMed, EMBASE, and Web of Science were searched from inception to March 2024. Studies with systematic reviews and meta-analyses that examined associations between HPV or HPV-associated genotypes infection and specific cancers were eligible for this review. The quality of the methodology was evaluated using A Measurement Tool to Assess systematic Reviews (AMSTAR). The credibility of the evidence was assessed using GRADE. The protocol was preregistered with PROSPERO (CRD42023439070). The umbrella review identified 31 eligible studies reporting 87 associations with meta-analytic estimates, including 1191 individual studies with 336,195 participants. Of those, 29 (93.5%) studies were rated as over moderate quality by AMSTAR. Only one association indicating HPV-18 infection associated with an increased risk of breast cancer (odds ratio [OR]=3.48, 95% confidence interval [CI]=2.24-5.41) was graded as convincing evidence. There were five unique outcomes identified as highly suggestive evidence, including HPV infection increased the risk of oral squamous cell carcinoma (OR=7.03, 95% CI=3.87-12.76), oesophageal cancer (OR=3.32, 95% CI=2.54-4.34), oesophageal squamous cell carcinoma (OR=2.69, 95% CI=2.05-3.54), lung cancer (OR=3.60, 95% CI=2.59-5.01), and breast cancer (OR=6.26, 95% CI=4.35-9.00). According to GRADE, one association was classified as high, indicating that compared with the controls in normal tissues, HPV infection was associated with an increased risk of breast cancer. The umbrella review synthesised up-to-date observational evidence on HPV infection with the risk of breast cancer, oral squamous cell carcinoma, oesophageal cancer, oesophageal squamous cell carcinoma, and lung cancer. Further larger prospective cohort studies are needed to verify the associations, providing public health recommendations for prevention of disease. National Key Research and Development Program of China, Natural Science Foundation of China, Outstanding Scientific Fund of Shengjing Hospital of China Medical University, and 345 Talent Project of Shengjing Hospital of China Medical University.

A Scoping Review of Complementary and Alternative Medicine for Human Papillomavirus Infections and Cervical Dysplasia.

The goal of this scoping review is to synthesize clinically relevant scientific literature on current complementary and alternative medications that address human papillomavirus (HPV) infections and cervical dysplasia. A systematic search of published studies was performed December 2021 for the following concepts: human papilloma virus, cervical dysplasia, and complementary and alternative medicine (CAM). Relevant publications were identified by searching Ovid MEDLINE ALL, Embase, Cochrane Library, AMED, and MEDLINE databases, in addition to clinical trial databases. Data were extracted based on specific study selection criteria and analyzed by 3 authors independently using Covidence software. A total of 2324 studies were identified of which 56 met inclusion criteria. Treatment outcomes measured regression of HPV, improvement of cervical cytology, and/or regression of histopathology with varied definitions of success across all studies. The CAM therapies found to have the most clinical benefit and best supporting data via randomized control trials were topical mushroom ( Coriolus versicolor) gel, oral and topical selenium therapies, and oral indol-3-carbinol. Adverse events were reported in only 28/56 (50%) of included studies. The evidence for treating HPV and cervical dysplasia with CAM is of low quality because of lack of standardized, clinically relevant treatment outcomes, lack of standardization of products, and minimal reporting on adverse and long-term effects. Future large, randomized control trials are needed to further assess efficacy and safety of CAM therapies to address HPV and cervical dysplasia.

Determination of Opinions on HPV Infection and HPV Vaccine among Nursing Students by Focus Group Discussion.

Purpose: This study aimed to determine nursing students' opinions about human papillomavirus (HPV) infection and HPV vaccine. Methods: This is a qualitative focus group discussion study, in which a state university in Western Turkey, undergraduate nursing students are recruited through purposive sampling. The research data were collected on an online platform with the focus group interview method by using the Participant Information Form and Semistructured Interview Form. Results: Three main themes (HPV infection/vaccine perception, severity perception, and suggestions and requests/facilitators) and eight subthemes were developed based on the thematic analysis of the research findings. Conclusions: According to the findings, it was concluded that nursing students' opinions on HPV infection and HPV vaccine were affected by factors related to cultural, religious, and sexual behaviors. Based on study results, it is suggested to organize national cervical screening programs to increase public's knowledge and awareness on the subject in accordance with the sociocultural norms of the society with the agreement and cooperation of educated health service providers, policy makers, and educators.

Special RCA based sensitive point‐of‐care detection of HPV mRNA for cervical cancer screening

AbstractDeveloping the sensitive point‐of‐care testing (POCT) of oncogenic nucleic acids from human papillomavirus (HPV) infection is essential in preventing cervical cancer, especially in resource‐limited settings. Rolling circle amplification (RCA) is attractive in achieving POCT via nucleic acid‐based aggregation under isothermal conditions. However, the influence of RCA product structure on the aggregation remains unexplored resulting in limited sensitivity. Here, a minimum secondary structured RCA technique (MSS‐RCA) is developed by designing a unique circular template, demonstrating significantly enhanced detection sensitivity with only one amplification step and one primer under isothermal conditions. The amplification efficiency of MSS‐RCA could be kinetically manipulated by controlling the secondary structure of the circular template. Introducing the invertase probe to MSS‐RCA, HPV16 E6/E7 nucleic acid target was detected with a personal glucose meter (PGM) with a sensitivity of 5 fm (50 zmol in 10 µL). This integrated MSS‐RCA‐PGM detection system was successfully applied to detect HPV16 E6/E7 mRNA extracted from 54 cervical swab samples reaching a positive predictive value of 100.00% and negative predictive values of 96.00% (77.77% to 99.40%, 95% CI). MSS‐RCA‐PGM provides a sensitive POCT platform for the detection of nucleic acid biomarkers for screening of cervical cancer or other diseases.

Clinical vaginal-microecology testing using double-fluorescence staining in patients with high-risk human papillomavirus infection

High-risk human papillomavirus (hrHPV) infection is associated with cervical cancer; imbalanced vaginal microecology may contribute to HPV progression. Currently used methods for clinical vaginal-microecology (CVM) testing are associated with several disadvantages, such as low accuracy and complicated operation. This retrospective study presents a novel testing method to examine vaginal microecology via double-fluorescence staining and explores the relationship between hrHPV and CVM. We analyzed 1242 patients who underwent hrHPV testing at our hospital over a two-month period; of these, 695 also underwent clinical vaginal-microecology testing (CVMT). Patients underwent routine leukorrhea detection (n=322), functional testing (n=277), and our novel double-fluorescence staining-based CVMT approach (n=376). Patients with hrHPV exhibited more epithelial cells, miscellaneous bacteria, and hyphae than those without hrHPV on double-fluorescence staining-based CVMT approach. Double-fluorescence staining was effective in identifying indicators of hrHPV infection and may serve as an auxiliary tool for clinical hrHPV screening.

Exposure to polycyclic aromatic hydrocarbons promotes the progression of low-grade cervical intraepithelial neoplasia: A population-based cohort study in China.

Low-grade cervical intraepithelial neoplasia (CIN1) is an early stage of cervical cancer development. Previously, we reported that exposure to polycyclic aromatic hydrocarbons (PAHs) increases the risk of cervical precancerous lesions, especially in females with a high-risk human papillomavirus (HR-HPV) infection. However, the effects of PAHs on CIN1 progression remain unclear. A community-based prospective cohort study was conducted to evaluate the role of exposure to PAHs in the progression of CIN1. A total of 564 patients diagnosed with CIN1 were followed-up at 6, 12, and 24 months, post-diagnosis, to determine CIN1 reversion, persistence, and progression. Exposure to PAHs was determined by the urine 1-hydroxipayrene (1-OHP) level. Our results showed that the 1-OHP level was significantly higher in patients with CIN1 persistence/progression than in those with reversion (P < .05). High exposure to PAHs increased the risk of CIN1 persistence/progression, with hazard ratios (HR), 95% confidence intervals (CI) of (1.62, 1.24-2.67), (1.98, 1.42-2.75), and (2.37, 1.61-3.49) at 6, 12, and 24 months, post-diagnosis, respectively. The effect was enhanced with HR-HPV positivity, as determined at 6 (1.82, 1.24-2.67), 12 (3.02, 1.74-5.23), and 24 (2.51, 1.48-4.26) months, post-diagnosis. Moreover, the predictive value of exposure to PAHs for CIN1 persistence/progression was higher in HR-HPV-positive patients than in HR-HPV-negative patients. The results revealed that exposure to PAHs facilitated the malignant progression of CIN1 and hindered its reversal, particularly in patients with HR-HPV infection. Our findings provide novel insights into early prevention and intervention targeting the initiation and progression of cervical neoplasia.

Placental human papillomavirus infections and adverse pregnancy outcomes

IntroductionKnowledge on prevalence and association of human papillomavirus (HPV) in third trimester placentae and adverse pregnancy outcomes is limited. We investigated the prevalence of placental HPV at delivery, explored urine HPV characteristics associated with placental HPV and whether placental HPV increased the risk adverse pregnancy outcomes. MethodsPregnant women were enrolled in the Scandinavian PreventADALL mother-child cohort study at midgestation. Human papillomavirus genotyping was performed on placental biopsies collected at delivery (n = 587) and first-void urine at midgestation and delivery (n = 556). Maternal characteristics were collected by questionnaires at gestational week 18 and 34. Adverse pregnancy outcomes were registered from chart data including hypertensive disorders of pregnancy, gestational diabetes mellitus and newborns small for gestational age. Uni- and multivariable regression models were used to investigate associations. ResultsPlacental HPV was detected in 18/587 (3 %). Twenty-eight genotypes were identified among the 214/556 (38 %) with midgestational urine HPV. Seventeen of the 18 women with placental HPV were midgestational HPV positive with 89 % genotype concordance. Midgestational high-risk-(HR)-HPV and high viral loads of Any- or HR-HPV were associated with placental HPV. Persisting HPV infection from midgestation to delivery was not associated with placental HPV. Adverse pregnancy outcomes were seen in 2/556 (0.4 %) of women with placental HPV. DiscussionIn this general cohort of pregnant women, the prevalence of placental HPV was 3 %, and midgestational urinary HPV 38 %. High HPV viral load increased the risk for placental HPV infections. We observed no increased risk for adverse pregnancy outcomes in women with placental HPV.

Transcriptionally Active Human Papillomavirus Infection in a Minority of Esophageal Squamous Cell Carcinomas in North America.

The role of Human papillomavirus (HPV) infection in esophageal squamous cell carcinoma (ESCC) is a topic of ongoing debate. This study used two screening approaches to look for evidence of HPV infection in esophageal squamous cell carcinoma. We initially checked for HPV infection in a randomly selected group of 53 ESCC cases. We did not detect any tumors positive for high-risk HPV. However, during clinical practice, we identified an HPV-positive ESCC in the distal esophagus, which tested positive for HPV16. This index case was TP53 wild-type, as determined by next-generation DNA sequencing (NGS). Since TP53 mutations are rare in other HPV-driven cancers, we improved our screening method by limiting our screen to a subset of ESCC cases without TP53 mutations. A second screen of 95 ESCCs (from 93 patients) sequenced by NGS revealed an additional 7 ESCCs with TP53 wild-type status (7.3% of the total). Of the 7 cases, 2 cases were found to be high-risk HPV positive. Both patients also tested positive for circulating cell-free HPV DNA and had a complete response to neoadjuvant chemoradiation. The index patient had microscopic residual tumor following neoadjuvant therapy. The patient underwent adjuvant immunotherapy and remained disease free after 22 months of surveillance. This study affirms the transcriptionally active status of high-risk HPV in a minority of ESCC patients in North America.

Human Papilloma Virus Vaccination and Cervical Screening in the Italian Regions: An Overview of the Current State of the Art.

Human Papilloma Virus (HPV) infection and HPV-related cancers can be prevented through vaccinations and mass cervical screening programmes. The Ministry of Health in Italy provides recommendations on primary and secondary prevention of HPV-related diseases, but the 19 Italian regions and 2 autonomous provinces have organisational and decision-making autonomy, with differences in the strategies for offering prevention. The aim of this study is to describe the HPV vaccination and cervical screening offered in all Italian regions. Regional official documents up until 31 December 2021 were first identified. Subsequently, primary and secondary prevention experts from each region were interviewed to validate the previously collected data. The National Immunisation Plan (NIP) 2017-2019 recommends HPV vaccination from the age of 11 for both sexes, with a coverage target of 95%. HPV vaccination is offered free of charge or co-payment. All regions have screening programmes for cervical cancer, using PAP or HPV-DNA tests every three to five years. All regions have an electronic registry for vaccination and screening status. All regions have developed awareness-raising campaigns. It is important to harmonise regional policies with the implementation of information systems integration. The collected data could enhance both regional and national public health initiatives, bolstering the resilience of vaccination programs.

Chimera RNA transcribed from integrated HPV18 genome with adjacent host genomic region promotes oncogenic gene expression through condensate formation.

Most cervical cancers are caused by human papillomavirus (HPV) infection. In HeLa cells, the HPV18 viral genome is integrated at chromosome 8q24.21 and activates transcription of the proto-oncogene c-Myc. However, the mechanism of how the integrated HPV genome and its transcribed RNAs exhibit transcription activation function has not been fully elucidated. In this study, we found that HPV18 transcripts contain an enhancer RNA-like function to activate proximal genes including CCAT1-5L and c-Myc. We showed that the human genome-integrated HPV18 genes are activated by transcription coregulators including BRD4 and Mediator. The transcribed HPV18 RNAs form a liquid-like condensate at chromosome 8q24.21 locus, which in turn accumulates RNA polymerase II. Moreover, we focused on a relatively uncharacterized transcript from the upstream region of CCAT1, named URC. The URC RNA is transcribed as a chimera RNA with HPV18 and is composed of the 3'-untranslated region of the HPV18 transcript. We experimentally showed that the URC contributes to stabilization of HPV18 RNAs by supplying a polyadenylation site for the HPV18 transcript. Our findings suggest that integrated HPV18 at 8q24.21 locus produces HPV18-URC chimera RNA and promotes tumorigenesis through RNA-based condensate formation.

Role of the epithelium in human papillomavirus and human immunodeficiency virus infections in the female genital tract.

Two-thirds of people living with human immunodeficiency virus type 1 (HIV-1) infection reside in Sub-Saharan Africa, where there are the highest prevalence and incidence rates of human papillomavirus (HPV) infection. Both infections are sexually transmitted and enter the body via the epithelium. This review describes the extent of involvement of the epithelium in each infection in the female genital tract. A narrative review was conducted on the role of the epithelium in HPV and HIV-1 infections. An intact epithelial barrier is the predominant form of protection against viral entry and infection, including from HIV-1 and HPV. HPV is an intraepithelial pathogen, and thus, its growth and amplification, which are dependent on squamous cell differentiation, occur in the epithelium. It gains entry to the basal cells of the stratified squamous epithelium via micro-abrasions or other epithelial injuries that expose the basement membrane. HIV-1, conversely, passes through the epithelium to infect subepithelial tissues. Following deposition of the HIV-1-containing inoculum into the lumen, the virus enters the mucosa through breaks in the epithelial barrier within hours of infection. Further, HIV-1 penetrates the epithelium via various mechanisms, including paracellular passage or across epithelial cells through transcytosis. The capture of the virus from the mucosal surface by intraepithelial and/or subepithelial target cells has also been documented. Epithelial disruption is the major pathogenetic pathway in HIV-1 and HPV infections. Therefore, biochemical compounds that strengthen the epithelial barrier must be prioritized to prevent these infections.

Impact of Human Papillomavirus (HPV) Infection on the Treatment Outcome of Concomitant Chemoradiotherapy (CRT) in Cervical Cancer

Background: Human Papilloma Virus (HPV) infection and its persistence are responsible for the development of cervical cancer (CaCx). Chemoradiotherapy (CRT) is the only treatment option, especially in advanced stages. However, it is not influenced by the status of HPV infection. CRT controls cancer growth along with mild to severe adverse effects. Objective: The aim of this study was to assess the HPV-associated risk factors and correlate them with chemoradiation therapy (CRT) response in cervical cancer. Methods: The study was undertaken in 103 histologically positive CaCx patients. Anthrodemographic and obstetric characterizations were conducted by face-to-face interviews, and HPV testing was done by conventional PCR. All the patients received a 40-50Gy total effective dose using tele‑ and brachytherapy. The treatment response, survivorship and statistical analysis were made using GraphPad Prism 9 and SPSS (ver.25.0). Results: Out of 103 patients, 84% were HPV infected, and 16% CaCx were HPV-negative. Advanced age, lower-middle socioeconomic status (SES), illiteracy, and patients from rural backgrounds were significantly higher in CaCx patients with HPV infection. Multiparity, irregular menstrual cycle, poor menstrual hygiene, and use of contraception were significantly associated with HPV positivity. Patients with HPV infection showed a better clinical response (P =0.031), alive vital status (P =0.007), and 59 months of median survival (P &lt;0.001) with a poor hazard ratio (HR 0.29 at 95% CI). Conclusion: HPV-infected CaCx patients showed better response to definitive chemoradiation therapy compared to HPV-negative with a poor hazard ratio. Therefore, HPV testing can potentially stratify CaCx patients for more effective therapeutic regimens, treatment assessments and follow-ups.

The Female Genital Tract Microbiome: a review

The human microbiome, a complex ecosystem consisting of microorganisms and their genetic material, profoundly impacts physiological processes crucial for human health. Among various niches within the human body, the female genital tract harbours a diverse microbial community, known as the vaginal microbiota, which plays a pivotal role in maintaining vaginal health and preventing infections. This review explores the intricate relationship between the vaginal microbiota and gynaecological conditions, including bacterial vaginosis, human papillomavirus (HPV) infection, cervical neoplasia, endometrial cancer, ovarian cancer, preterm birth, and infertility. Changes in the composition of the vaginal microbiota, known as dysbiosis, have been associated with a higher risk of these conditions. Notably, dysbiosis characterized by a reduction in protective Lactobacillus species and an increase in anaerobic organisms is associated with bacterial vaginosis, HPV infection persistence, and neoplastic development. Furthermore, alterations in the vaginal microbiota during pregnancy have implications for gestational outcomes, with a low frequency of lactobacilli predisposing women to preterm birth. Moreover, abnormal vaginal flora has been implicated in female infertility, affecting embryo implantation, tubal factors and pregnancy outcomes. Although there has been progressing in understanding the role of the vaginal microbiome in gynaecological health, additional research, particularly randomized controlled trials, is necessary to clarify the underlying mechanisms and devise targeted therapies.

From primary HPV infection to carcinoma in situ: A mathematical approach to cervical intraepithelial neoplasia

AbstractCervical intraepithelial neoplasia (CIN) is the development of abnormal cells on the surface of the cervix, caused by a human papillomavirus (HPV) infection. Although in most of the cases it is resolved by the immune system, a small percentage of people might develop a more serious CIN which, if left untreated, can develop into cervical cancer. Cervical cancer is the fourth most common cancer in women globally, for which the World Health Organization (WHO) recently adopted the Global Strategy for cervical cancer elimination by 2030. With this research topic being more imperative than ever, in this paper, we develop a nonlinear mathematical model describing the CIN progression. The model consists of partial differential equations describing the dynamics of epithelial, dysplastic, and immune cells, as well as the dynamics of viral particles. We use our model to explore numerically three important factors of dysplasia progression, namely, the geometry of the cervix, the strength of the immune response, and the frequency of viral exposure.

Prevalence of HPV in Oral Squamous Cell Carcinoma Through p16 IHC: A Hospital-Based Study in Eastern India

Abstract Context: Oral squamous cell carcinoma (OSCC), the third most prevalent solid cancer in India with 45% incidence, is associated with 20%–50% of cases having human papillomavirus (HPV) infection; however, the current role of HPV in managing OSCC remains unclear, particularly in high-incidence areas such as Eastern India. Aim: The study aims to determine the prevalence of HPV in OSCC patients and evaluate its role as an independent risk factor in the progression of OSCC. Settings and Design: This cross-sectional study, conducted in an Eastern Indian tertiary care hospital, involved 140 identified and treated OSCC patients. Materials and Methods: Immunohistochemistry (IHC) was used to determine HPV immunoreactivity using the marker p16. The data were analyzed using SPSS version 27.0 with a significance level of P &lt; 0.05. Results: Among 140 patients, 11 showed strong P16 positivity (&gt;70%) for HPV, resulting in a prevalence rate of 7.86%. However, no statistically significant association of HPV (p16 positivity) with any groups was found. Interestingly, all P16-positive patients in our study had a history of tobacco use (9.5%), suggesting that HPV may not be considered an independent factor for oral cancer. Conclusion: In our cases, p16 positivity is seen in 7.85% of cases. This finding suggests that further sub-analysis concerning p16 as a prognostic marker and its therapeutic implication is further required in oral cancer. Correlation with PCR is also required to substantiate TNM staging of p16 by the IHC method.

The Prognostic Value of Human Papillomavirus Status in Penile Cancer: Outcomes From a Norwegian Cohort Study

IntroductionPenile squamous cell carcinoma (PSCC) can develop from human papillomavirus (HPV) infection. This study investigates if the prognostic value of the TNM stage groups or the components tumor stage (pT), grade of differentiation (Grade), lymphovascular invasion (LVI), and nodular stage (pN) depend on HPV status. Also, whether the value of tumor parameters (pT, Grade, and LVI) for predicting node-positive disease depends on HPV status was investigated. Patients and MethodsStored tumor tissue from 226 patients treated for PSCC in Western Norway between 1973 and 2023 was investigated for HPV DNA. Histopathological variables were reevaluated according to the current TNM classification. Disease course was registered from hospital records. Inclusion of an interaction term between HPV and TNM stage groups in Cox regression enabled analysis of whether cancer-specific survival (CSS) of the stage groups depended on HPV status. This was also done separately for pT, Grade, LVI, and pN. Logistic regression with interaction terms between HPV and the tumor parameters were used to investigate if their predictive value depended on HPV status. ResultsHPV DNA was detected in 43% of the tumors. Stratified by HPV status, there was no significant interaction term in the Cox regression between HPV status and TNM stage groups (P = .74). Similar results were found for pT (P = .94), Grade (P = .08), LVI (P = .91) and pN (P = .77). Moreover, there were no significant interaction terms in the logistic regression between HPV status and the tumor parameters pT, Grade, and LVI (all P > .2). ConclusionsThis study found that prognosis of the TNM stage groups and the components pT, Grade, LVI, and pN were not modified by HPV in PSCC. The value of pT, Grade, and LVI for predicting lymph node-positive disease was not affected by HPV status.

Comparison of Long-Term Outcomes of Surgical Treatment of Human Papillomavirus-Dependent Neoplastic Lesions in Patients With Chronic Immunosuppression After Allogenic Organ Transplantation and Patients With Primary or Acquired Immunodeficiency—A One-Center Experience

Immunodeficiency predisposes to severe manifestations of human papillomavirus (HPV) infection, including extensive, recalcitrant anogenital lesions and their progression towards carcinomas. This holds for primary and acquired immunodeficiencies, and post-transplant immunosuppressive therapy. About 50% to 90% of patients receiving chronic immunosuppression after allogenic transplantation develop HPV-associated lesions within 4 to 5 years, comprising 10% to 15% of patients presenting with (pre)cancerous HPV-dependent anogenital lesions. Immunodeficiency is one of the highest risk factors associated with severe clinical manifestations of HPV-associated cancers. The primary objective of this work is to compare the long-term therapeutic effectiveness of surgical intervention for HPV-dependent lesions in transplant recipients undergoing chronic immunosuppression and patients burdened with primary or acquired immunodeficiencies. Two groups of 30 patients (selected for most extensive presentations of HPV-dependent neoplastic anogenital lesions), who underwent surgical treatment of these lesions were followed up for 3 to 5 years. The first group comprised patients who qualified and underwent kidney or liver transplantation (10 for a rare disease indication) and are under chronic immunosuppressive regimens. The second group comprised patients burdened by primary or acquired immunodeficiency (15 each). The recurrence rate in the follow-up period was the primary compared parameter. The recurrence rate was higher in the second group, amounting to >15%. For the first group a <5% recurrence rate was observed for recipients without rare disease indications, compared to <15% for recipients with such indications. The importance of rapid surgical intervention and the need for postoperative monitoring for recurrence is highlighted. Chronic immunosuppression demonstrates high relative safety and efficacy in terms of HPV-dependent anogenital lesion recurrence.

A Systematic Review of Knowledge, Attitudes, and Factors Influencing HPV Vaccine Acceptance Among Adolescents, Parents, Teachers, and Healthcare Professionals in the Middle East and North Africa (MENA) Region.

Human Papillomavirus (HPV) infection is the most common sexually transmitted infection, affecting both men and women globally. Men and women are at risk of type HPV16 and HPV18 viruses leading to cervical, anal, vulvar, and oropharyngeal cancers. The HPV vaccines are highly effective in preventing various strains of HPV infection, and effective vaccines are available only in the Middle East and North Africa (MENA) region. Hence, this systematic review explored knowledge and attitudes toward HPV infection and HPV vaccination and factors influencing HPV vaccination uptake among the MENA populations. Various databases, such as Medline, Science Direct, CINHAL, EBSCO, PsycINFO, and PubMed, were systematically searched to include English studies assessing knowledge, attitudes toward HPV infection, and factors influencing HPV vaccination acceptance in the MENA region. Twenty-two papers met the inclusion criteria. The number of participants ranged from 99 to 7223. While knowledge, attitude, and vaccine hesitancy association factors were generally reported in cross-sectional studies, the HPV vaccine acceptancy over time from longitudinal studies was mixed and inconclusive due to inadequate information on HPV infection and vaccination, the cost of the vaccine, cultural beliefs, and safety concerns. Results demonstrated that low HPV vaccine acceptance is due to a lack of HPV understanding among the MENA population, coupled with access issues. Factors such as awareness, confidence in vaccination, and involvement in decision-making positively influence vaccine uptake. Therefore, tailored programs addressing vaccine hesitancy in the MENA communities are necessary.