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The Oncologist Jul 2023Human papillomavirus (HPV) types 16/18 drive oncogenesis for most patients with cervical, anal, and penile cancers. MEDI0457, a therapeutic DNA vaccine containing...
BACKGROUND
Human papillomavirus (HPV) types 16/18 drive oncogenesis for most patients with cervical, anal, and penile cancers. MEDI0457, a therapeutic DNA vaccine containing plasmids for E6 and E7 HPV-16/18 viral oncogenes and IL-12 adjuvant, is safe and provokes an immune response against E6/E7. We tested MEDI0457 with the anti-PD-L1 antibody durvalumab for patients with HPV-associated cancers.
METHODS
Patients with recurrent/metastatic, treatment-refractory HPV-16/18 cervical cancer, or rare HPV-associated (anal and penile) cancers were eligible. Prior immune checkpoint inhibition was not permitted. Patients received MEDI0457 7 mg intramuscularly (weeks 1, 3, 7, 12, and every 8 weeks thereafter) and durvalumab 1500 mg intravenously every 4 weeks. The primary endpoint was overall response (RECIST 1.1). In this Simon two-stage phase 2 trial (Ho: p < 0.15; Ha: p ≥ 0.35), ≥2 responses were needed in both cervical and non-cervical cohorts during the first stage for the trial to proceed to stage 2 with an additional 25 patients (34 total) enrolled.
RESULTS
Twenty-one patients (12 cervical, 7 anal, and 2 penile) were evaluable for toxicity and 19 for response Overall response rate was 21% (95% CI, 6%-46%) among evaluable patients. Disease control rate was 37% (95% CI, 16%-62%). Median duration of response among responders was 21.8 months (95% CI, 9.7%-not estimable). Median progression-free survival was 4.6 months (95% CI, 2.8%-7.2%). Median overall survival was 17.7 months (95% CI, 7.6%-not estimable). Grades 3-4 treatment-related adverse events occurred in 6 (23%) participants.
CONCLUSIONS
The combination of MEDI0457 and durvalumab demonstrated acceptable safety and tolerability in patients with advanced HPV-16/18 cancers. The low ORR among patients with cervical cancer led to study discontinuation despite a clinically meaningful disease control rate.
Topics: Female; Humans; Human Papillomavirus Viruses; Uterine Cervical Neoplasms; Papillomavirus Infections; Human papillomavirus 16; Neoplasm Recurrence, Local; Human papillomavirus 18
PubMed: 37104874
DOI: 10.1093/oncolo/oyad085 -
JAMA Oncology Dec 2023Human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma has an overall favorable prognosis, yet a subset of patients will experience devastating... (Review)
Review
IMPORTANCE
Human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma has an overall favorable prognosis, yet a subset of patients will experience devastating disease recurrence. Current surveillance standards for detection of recurrent disease are imperfect. There is growing interest in improving detection of recurrent disease through the use of plasma-based assays able to detect circulating tumor HPV DNA.
OBSERVATIONS
Although most circulating tumor HPV DNA assays remain in the research domain, the circulating tumor tissue-modified viral HPV DNA assay became commercially available in the United States in early 2020 and has been increasingly used in the clinical setting. With the rapidly increasing incidence of HPV-positive oropharyngeal squamous cell carcinoma and concomitant expansion of biomarker capabilities for this disease, it is critical to reexamine current posttreatment surveillance practices and to determine whether emerging technologies may be used to improve outcomes for a growing survivor population. However, caution is advised; it is not yet known whether biomarker-based surveillance is truly beneficial, and as is true with any intervention, it has the capacity to cause harm.
CONCLUSIONS AND RELEVANCE
Using Margaret Pepe's classic 5 phases of biomarker development for early detection of cancer as a framework, this article reviews the current state of knowledge, highlights existing knowledge gaps, and suggests research that should be prioritized to understand the association between biomarker-based surveillance and patient outcomes. Specific attention is paid to the commercially available tumor tissue-modified viral HPV DNA assay, given its increasing clinical use. This review may serve as a road map for future research and a guide for clinicians considering its adoption in practice. Enrollment of patients into clinical trials incorporating biomarker-based surveillance should be prioritized.
Topics: Humans; Squamous Cell Carcinoma of Head and Neck; Oropharyngeal Neoplasms; Papillomavirus Infections; Neoplasm Recurrence, Local; Head and Neck Neoplasms; Biomarkers; DNA, Viral; Papillomaviridae
PubMed: 37824111
DOI: 10.1001/jamaoncol.2023.4042 -
The Journal of Infectious Diseases Oct 2023The etiologic link between human papillomavirus (HPV) and lung cancer is still controversial. (Meta-Analysis)
Meta-Analysis
BACKGROUND
The etiologic link between human papillomavirus (HPV) and lung cancer is still controversial.
METHODS
PubMed and Cochrane databases were searched from inception to December 2020 to identify studies on the infection of HPV in lung cancer. We calculated the attributable proportion of HPV in lung cancer by pooling the infection of cases positive for both HPV DNA and biomarkers of carcinogenesis that may be induced by HPV (E6/E7 messenger RNA or p16INK4a).
RESULTS
A total of 117 studies, comprising data of 12 616 lung cancer cases from 22 countries across 5 continents, were included. The overall HPV DNA positivity in primary lung cancer cases worldwide was 16.4% (95% confidence interval, 12.7%-20.5%). HPV DNA positivity of lung cancer varied significantly by pathological type and geographic region. Notably, the expression rate of p16INK4a is significantly higher than the positivity of HPV DNA and of HPV E6/E7 mRNA (P < .05). The estimate of HPV attributable proportion defined by expression of E6/E7 mRNA was 0 and of p16INK4a was 7.3%.
CONCLUSIONS
The data in this systematic review is robust enough to contradict the possible participation of HPV in lung cancer carcinogenesis. Prophylactic vaccines targeting HPV cannot have the potential to prevent lung cancer.
Topics: Female; Humans; Uterine Cervical Neoplasms; Oncogene Proteins, Viral; Human Papillomavirus Viruses; Papillomavirus Infections; RNA, Messenger; DNA, Viral; Lung Neoplasms; Carcinogenesis; Papillomavirus E7 Proteins; Papillomaviridae; RNA, Viral
PubMed: 37506267
DOI: 10.1093/infdis/jiad295 -
JNMA; Journal of the Nepal Medical... Aug 2023Cervical cancer is one of the leading causes of morbidity and mortality among women globally as well as in Nepal. It is attributable to persistent infection by high-risk...
Knowledge of Cervical Cancer Screening and Prevention by Human Papillomavirus Deoxyribonucleic Acid and Human Papillomavirus Vaccination among Women Attending a Tertiary Care Centre.
INTRODUCTION
Cervical cancer is one of the leading causes of morbidity and mortality among women globally as well as in Nepal. It is attributable to persistent infection by high-risk human papillomavirus, especially human papillomavirus-16 and human papillomavirus-18. The aim of this study was to find out the knowledge of cervical cancer screening and prevention by human papillomavirus deoxyribonucleic acid and human papillomavirus vaccination among women attending a tertiary care centre.
METHODS
A descriptive cross-sectional study was conducted in patients attending the outpatient Department of Gynaecology in a tertiary care centre from 18 March to 30 April 2023. After calculating sample size and taking a convenience sampling a survey questionnaire on knowledge of Cervical Cancer Screening and Prevention by Human Papillomavirus Deoxyribonucleic Acid and Human Papillomavirus Vaccination was collected. The point estimate was calculated at a 95% confidence interval.
RESULTS
Among 508 women, 42 (8.25%) (5.86-10.64, 95% Confidence Interval) had knowledge of cervical cancer screening and prevention by human papillomavirus deoxyribonucleic acid and human papillomavirus vaccination. According to the questionnaires with a total sample of 508, 164 (32.28%) know about cervical cancer, 15 (2.95%) know about HPV infection, 14 (2.76%) know about HPV infection causes cervical cancer, and 21 (4.13%) know about HPV transmitted through multiple sex partners.
CONCLUSIONS
The knowledge of cervical cancer screening and prevention by human papillomavirus deoxyribonucleic acid and human papillomavirus vaccination among women is very low. This study recommends having a health education and awareness programme on it to increase knowledge.
KEYWORDS
cervical cancer; human papillomavirus; pap smear; sexual intercourse; vaccination.
Topics: Female; Humans; Uterine Cervical Neoplasms; Papillomavirus Infections; Human Papillomavirus Viruses; Early Detection of Cancer; Cross-Sectional Studies; Tertiary Care Centers; Health Knowledge, Attitudes, Practice; Papillomaviridae; Papillomavirus Vaccines; Vaccination; DNA
PubMed: 38289809
DOI: 10.31729/jnma.8248 -
Viruses Sep 2023Cervical cancer, a major health concern among women worldwide, is closely linked to human papillomavirus (HPV) infection. This study explores the evolving landscape of...
Cervical cancer, a major health concern among women worldwide, is closely linked to human papillomavirus (HPV) infection. This study explores the evolving landscape of HPV molecular epidemiology in Taiwan over a decade (2010-2020), where prophylactic HPV vaccination has been implemented since 2007. Analyzing data from 40,561 vaginal swab samples, with 42.0% testing positive for HPV, we reveal shifting trends in HPV genotype distribution and infection patterns. The 12 high-risk genotypes, in order of decreasing percentage, were HPV 52, 58, 16, 18, 51, 56, 39, 59, 33, 31, 45, and 35. The predominant genotypes were HPV 52, 58, and 16, accounting for over 70% of cases annually. The proportions of high-risk and non-high-risk HPV infections varied across age groups. High-risk infections predominated in sexually active individuals aged 30-50 and were mixed-type infections. The composition of high-risk HPV genotypes was generally stable over time; however, HPV31, 33, 39, and 51 significantly decreased over the decade. Of the strains, HPV31 and 33 are shielded by the nonavalent HPV vaccine. However, no reduction was noted for the other seven genotypes. This study offers valuable insights into the post-vaccine HPV epidemiology. Future investigations should delve into HPV vaccines' effects and their implications for cervical cancer prevention strategies. These findings underscore the need for continued surveillance and research to guide effective public health interventions targeting HPV-associated diseases.
Topics: Humans; Female; Uterine Cervical Neoplasms; Human Papillomavirus Viruses; Papillomavirus Infections; Molecular Epidemiology; Papillomavirus Vaccines; Papillomaviridae; Genotype; Human papillomavirus 31; Prevalence
PubMed: 37896791
DOI: 10.3390/v15102015 -
The American Journal of Surgical... Aug 2023Recently, the World Health Organization (WHO) recognized the existence of human papillomavirus (HPV)-independent invasive cervical squamous cell carcinoma (SCC), but...
Recently, the World Health Organization (WHO) recognized the existence of human papillomavirus (HPV)-independent invasive cervical squamous cell carcinoma (SCC), but HPV-independent precursor lesions were not included due to the lack of description of this rare entity. We present the histologic spectrum of highly differentiated squamous HPV-negative and p16 ink4a -negative precursor lesions adjacent to and/or preceding invasive HPV-negative cervical SCC in 3 patients. The histologic features resembled those described for vulvar HPV-negative precursor lesions. One precursor featured a proliferation of atypical basal keratinocytes with mitotic activity, premature squamatization in elongated epithelial rete, and mostly regular superficial squamous differentiation with TP53 mutation and immunohistochemical p53 overexpression termed differentiated cervical intraepithelial neoplasia (d-CIN). The other 2 precursors included verruciform acanthosis with plump rete, minimal atypia, and an EGFR mutation that resembled vulvar acanthosis with altered differentiation, and an exophytic papillary proliferation with a PIK3CA mutation resembling the differentiated exophytic vulvar intraepithelial lesion. Two precursors that preceded the invasive SCC harbored an additional pathogenic SMARCB1 mutation. The cytologic smears of d-CIN revealed 3-dimensional branched basaloid tubular structures and eosinophilic squamous cell clusters mimicking the histologic features. In conclusion, highly differentiated cervical HPV-negative precursors are characteristic intraepithelial squamous lesions with somatic mutations that resemble those described in vulvar HPV-independent carcinogenesis. For optimal reproducibility, we propose a simplistic classification of these HPV-negative cervical precursors in TP53 -mutated d-CIN and p53 wild-type verruciform intraepithelial neoplasia.
Topics: Female; Humans; Tumor Suppressor Protein p53; Papillomavirus Infections; Reproducibility of Results; Vulvar Neoplasms; Carcinoma in Situ; Carcinoma, Squamous Cell; Papillomaviridae; Uterine Cervical Dysplasia; Cyclin-Dependent Kinase Inhibitor p16
PubMed: 37283469
DOI: 10.1097/PAS.0000000000002067 -
Journal of Medical Virology Jan 2024Human papillomavirus (HPV) infection can lead to HPV-related cancer in men, including the anus, penile, and oropharyngeal cancers and precancerous lesions. This study...
Human papillomavirus (HPV) infection can lead to HPV-related cancer in men, including the anus, penile, and oropharyngeal cancers and precancerous lesions. This study retrospectively investigated HPV prevalence and genotype distribution in Liaocheng men between 2016 and 2022. The total HPV positive rate was 64.87% (2388/3681, 95% confidence interval [CI]: 63.32%-66.40%), where high risk (HR)-HPV and low risk (LR)-HPV accounted for 42.49% (1564/3681, 95% CI: 40.90%-44.09%) and 69.71% (2566/3681, 95% CI: 68.20%-71.17%), respectively. The mixed HPV infection rate of two and more genotypes was 35.72%. The infection rate of HR-HPV increased with the number of positive cases annually from 2016 (16.91%) to 2022 (46.59%). The most common HR-HPV genotypes were HPV16 (11.60%), HPV52 (6.95%), and HPV59 (6.28%), whereas the least common HR-HPV was HPV26. The most common LR-HPV genotypes were HPV6 (56.99%), HPV11 (23.79%), and HPV43 (6.37%). The 9 v HPV vaccine preventable for LR-HPV and HR-HPV accounted for 80.78% and 30.40%, respectively, in this study. Most HPV-positive patients aged 1-86 were in the 30-39 age group. This study confirmed that HPV prevalence in Liaocheng men was common and diverse. HPV16, HPV52, and HPV59 are widely distributed in Liaocheng men, and the male HR-HPV infection rate remained high in this region. Regarding public health and cancer prevention, it is recommended and effective to include the HPV vaccination in the national vaccination program for men.
Topics: Female; Humans; Male; Adult; Papillomavirus Infections; Uterine Cervical Neoplasms; Prevalence; Retrospective Studies; Human papillomavirus 18; Papillomaviridae; Human papillomavirus 16; Genotype
PubMed: 38178597
DOI: 10.1002/jmv.29360 -
Veterinary Pathology Nov 2023papillomavirus 1 (EdPV1) and papillomavirus 2 (EdPV2) are associated with cutaneous papillomas in North American porcupines (). This study defined gross,...
papillomavirus 1 (EdPV1) and papillomavirus 2 (EdPV2) are associated with cutaneous papillomas in North American porcupines (). This study defined gross, histopathologic, and molecular characteristics of viral papillomas in 10 North American porcupines submitted to the New York State Animal Health Diagnostic Center. Investigation for the presence of EdPV1 and EdPV2 DNA via polymerase chain reaction (PCR) was performed in 9 of the 10 (90.0%) porcupines, and all porcupines were investigated for the detection and localization of EdPV1 and EdPV2 E6 and E7 nucleic acid via chromogenic in situ hybridization (CISH). Next-generation sequencing (NGS) was performed in 2 porcupines. Papillomas were diagnosed on the muzzle ( = 4), caudal dorsum ( = 1), upper lip ( = 1), chin ( = 1), gingiva ( = 2), and nasal planum ( = 1). Histologically, the lesions consisted of hyperplastic epidermis or epithelium with orthokeratotic keratin, prominent keratohyalin granules, and intranuclear inclusion bodies. PCR identified EdPV1 in 6 of 9 samples and EdPV2 in the remaining 3 samples. NGS resulted in 100% genome coverage of EdPV1 and 76.20% genome coverage of EdPV2 compared with GenBank reference sequences, with 99.8% sequence identity to the complete EdPV2 L1 gene of a novel subtype recently identified in France. Hybridization patterns in 9 of the 10 (90.0%) porcupines were characterized by strong nuclear signals in the superficial epidermis, with strong nuclear and punctate cytoplasmic signals in the stratum spinosum and basale. In one animal, CISH suggested dual EdPV1 and EdPV2 infection.
Topics: Animals; Porcupines; Papillomaviridae; North America; Papilloma; France; Rodent Diseases
PubMed: 37264637
DOI: 10.1177/03009858231176564 -
Virology Journal Mar 2024Human papilloma virus (HPV) infection among female is the cause of cervical cancer and genital warts. In China, the HPV vaccination rate and the target population...
BACKGROUND
Human papilloma virus (HPV) infection among female is the cause of cervical cancer and genital warts. In China, the HPV vaccination rate and the target population screening rate among females are low, and the aims of this study on the genotype distribution and prevalence of HPV infection were to provide more targeted strategies for the prevention and treatment of cervical cancer and HPV-related diseases.
METHODS
Polymerase chain reaction-reverse dot blot (PCR-RDB) was adopted for HPV genotyping test, the prevalence and 23 genotypes distribution of HPV infections among 181,705 women in Chengdu from 2013 to 2020 were analysed.
RESULTS
The overall prevalence rate of HPV infection among 181,705 cases was 23.28%, the prevalence of HR-HPV at the age group < 20 years, 60-69 years and ≥ 70 years were higher than the overall prevalence.The prevalence of HPV showed a bimodal U-shaped curve with age; the first and second peak common occurred among females < 20 years old (42.97%) and 60-69 years old (37.56%), respectively.The top five genotypes of HPV infection among females in Chengdu were HPV52/16/58/81/53. Single infection (73.26%) was the main HPV infection pattern, followed by double infection (19.17%) and multiple infection (7.57%), the infection rate of HPV showed a gradual declined as the patterns of HPV coinfections increased, low-risk and high-risk coinfection was higher in low-risk HPV infection (43.68%) and lower in high-risk HPV infection (13.59%). The prevalence of genotypes - 6 and - 81 infection was the second highest at the age group of 20 and 40-59, respectively, while the prevalence of HPV16 was the highest at the age group of ≥ 70 among 23 genotypes among the 181,705 women.
CONCLUSIONS
The prevalence of HPV infections among women in Chengdu is higher than domestic certain developed citys, among the five vaccines available, nonavalent vaccine is more suitable for Chengdu females. For young females prioritizing vaccination is essential in the current context.Double screening for HPV DNA is important in middle-aged women (30-49 years), and screening should not be lacking in older women (> 65 years). Additionally,for patients with genital warts, it is necessary to screen for high-risk HPV infection and provide appropriate management and treatment. Given the limitations of this study, future HPV research should aim to achieve full coverage of the target population, and our studies should also include cellular or pathological data of HPV-positive cases, vaccination rates, and various lifestyle details.
Topics: Middle Aged; Humans; Female; Aged; Young Adult; Adult; Papillomavirus Infections; Uterine Cervical Neoplasms; Prevalence; Papillomaviridae; Condylomata Acuminata; China; Genotype
PubMed: 38429823
DOI: 10.1186/s12985-024-02317-x -
Journal of Medical Virology Oct 2023Human papillomavirus (HPV) is one of the most common sexually transmitted infections nationwide. The COVID-19 pandemic has greatly influenced on the HPV prevention...
Human papillomavirus (HPV) is one of the most common sexually transmitted infections nationwide. The COVID-19 pandemic has greatly influenced on the HPV prevention project. The objective of this study was to examine the influence of the pandemic on HPV prevalence and genotype distribution in Beijing, China. A total of 44 401 genital swabs were obtained from outpatients at Peking Union Medical College Hospital during two distinct periods: the prepandemic stage from January 2017 to December 2019 and the pandemic stage from January 2020 to December 2022. During the prepandemic and pandemic stages, a total of 33 531 and 10 870 swabs were respectively collected. Fifteen high-risk HPV (HR-HPV) DNA type and a combination of two low-risk (LR-HPV) types (6/11) of genital swabs were detected to compare the HPV infection rates and genotype distributions in two stages. The results showed that the pandemic period witnessed a decrease in the overall HPV infection rate from 33.43% (11 245/33 531) to 29.43% (5527/18 780) compared to the prepandemic. There were statistically significant differences in infection rates between females and males (p < 0.05). Single infection was the predominant type while multiple infection was more prevalent in males than females in both prepandemic and pandemic periods. HR-HPV infection constituted the majority of infections and cannot be disregarded. The distribution of HR-HPV genotypes exhibited little variation before and after the outbreak, but there were some differences between females and males. HPV 16, 52, 58, 56, and 66 were the most commonly detected genotypes in females, whereas HPV 16, 52, 51, 58, and 18 were frequently detected in males. Additionally, HPV 6/11 exhibited a higher prevalence in males than in females. Notably, the age group of 31-40 years old exhibited the highest prevalence of HPV and the lowest infection rate was detected among individuals aged ≤20 years (p < 0.05), which remained relatively consistent before and during the pandemic. These findings underscore the importance of monitoring the trend of HPV epidemic and offer valuable insights for the prevention, treatment, and scientific investigation of HPV in the post-COVID-19 era.
Topics: Male; Female; Humans; Adult; Papillomavirus Infections; Pandemics; Prevalence; Beijing; COVID-19; Genotype; Papillomaviridae; China; Uterine Cervical Neoplasms
PubMed: 37815056
DOI: 10.1002/jmv.29155