HPV distribution in cervical cancer in Portugal. A retrospective study from 1928 to 2005

Objectives: To determine human papillomavirus (HPV) types in invasive cervical cancer in Portugal. Methods: Cases diagnosed at the Institute Portugues de Oncologia de Lisboa de Francisco Gentil from the year 1928 to 2005 were selected for HPV DNA detection and genotyping using SPF10/DEIA/LiPA25 system. Results: Of the 1214 samples that were considered appropriate for HPV detection, 714 (58.8%; 95% CI: 56.0-61.6%) were positive for HPV DNA. This detection rate varied being lower in the first 3 decades (31.3%; 50.1%; 46.5%) and higher in the last decades (77.4-95.1%). This difference was due probably to the fixative used in the first three decades. The five most common types identified among HPV positive cases were HPV16 (58.2%), HPV18 (9.2%), HPV33 (6.2%), HPV45 (4.7%) and HPV31 (4.4%). Multiple infections were detected in 2.8% of the cases. HPV16 and 18 accounted for 67.4% of infections. There were no statistically significant changes of these types over the studied period. An increase at patient's age at diagnosis was observed in the last decades (p < 0.001). Conclusion: HPV16 and 18 accounts for almost 70% of cervical cancers in all 9 decades studied and support data that effective vaccination against these 2 types will reduce the cervical burden in Portuguese women

Estimation of the overall burden of cancers, precancerous lesions, and genital warts attributable to 9-valent HPV vaccine types in women and men in Europe

Background: In addition to cervical cancer, human papillomavirus (HPV) is responsible for a significant proportion of cancers and precancerous lesions of the vulva, vagina, anus, penis, head and neck, as well as genital warts. We estimated the annual number of new cases of these diseases attributable to 9-valent HPV vaccine types in women and men in Europe. Methods: The annual number of new cancers of the cervix, vulva, vagina, anus, penis, and selected head and neck sites in the population of the European Medicines Agency territory was estimated based on age-specific incidence rates extracted from Cancer Incidence in 5 Continents, Volume X and Eurostat population data for 2015. The annual number of new cancers attributable to 9-valent HPV vaccine types was estimated by applying the HPV attributable fraction from reference publications based on a large European multicenter study. For non-cervical cancers, HPV attributable fractions were based on oncogenically-active HPV infections only (i.e., detection of HPV DNA and either mRNA and/or p16 positivity). For precancerous lesions of the cervix, vulva, vagina, and anus, and for genital warts, previously published estimations were updated for the 2015 population. Results: The annual number of new cancers attributable to 9-valent HPV vaccine types was estimated at 47,992 (95% bound: 39,785-58,511). Cervical cancer showed the highest burden (31,130 cases), followed by head and neck cancer (6,786 cases), anal cancer (6,137 cases), vulvar cancer (1,466 cases), vaginal cancer (1,360 cases), and penile cancer (1,113 cases). About 81% were estimated to occur in women and 19% in men. The annual number of new precancerous lesions (CIN2+, VIN2/3, VaIN2/3, and AIN2/3) and genital warts attributable to 9-valent HPV vaccine types was estimated at 232,103 to 442,347 and 680,344 to 844,391, respectively. Conclusions: The burden of cancers associated with 9-valent HPV vaccine types in Europe is substantial in both sexes. Head and neck cancers constitute a heavy burden, particularly in men. Overall, about 90% of HPV-related cancers, 80% of precancerous lesions, and 90% of genital warts are expected to be attributable to 9-valent HPV vaccine types each year, demonstrating the important preventive potential of the 9-valent HPV vaccine in Europe

The impact of p16(ink4a) positivity in invasive vulvar cancer on disease-free and disease-specific survival, a retrospective study

Purpose To evaluate HPV and p16(ink4a) status as prognostic factors in patients with invasive vulvar cancer. Methods Retrospective analysis of disease-free (DFS) and disease-specific survival (DSS) of patients with invasive vulvar cancer at a single tertiary care center. Histology, HPV and p16(ink4a) status were evaluated in the context of a global multicenter trial. Logistic regression models were performed to identify the impact of p16(ink4a) positivity. Results 135 patients were included in the analysis. 32 (23.7%) showed a p16(ink4a) expression of over 25%. Disease-free and disease-specific survival was longer in p16(ink4a) positive patients (23 vs. 10 months, p = 0.004, respectively, 29 vs. 21 months, p = 0.016). In multivariate analysis, p16(ink4a) positivity was an independent parameter for DFS (p = 0.025, HR: 2.120 (1.100-4.085)), but not for DSS (p = 0.926, HR: 1.029 (0.558-1.901), in contrast to age and tumor stage. Conclusions Age and tumor stage negatively affect survival. However, disease-free survival is significantly longer in patients with p16(ink4a) positive invasive vulvar cancer

Immune biomarkers of response to immune-checkpoint inhibitors in head and neck squamous cell carcinoma

Anti-programmed cell death protein 1 (PD-1) agents have become the standard of care for platinum-refractory recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) and are currently being evaluated in various disease settings. However, despite the gain in overall survival seen in some of the clinical trials, the majority of patients display primary resistance and do not benefit from these agents. Taking into consideration the potentially severe immune-related toxicities and their high cost, the search for predictive biomarkers of response is crucial. Besides Programmed death ligand-1 (PD-L1) expression, other biomarkers such as immune infiltration, tumor mutational burden or immune-gene expression profiling have been explored, but none of them has been validated in this disease. Among these, the microbiota has recently garnered tremendous interest since it has proven to influence the efficacy of PD-1 blockade in some tumor types. With the accumulating evidence on the effect of the microbiota in HNSCC tumorigenesis and progression, the study of its potential role as a predictive immune biomarker is warranted. This review examines the available evidence on emerging immune predictive biomarkers of response to anti-PD-1/PD-L1 therapy in HNSCC, introducing the microbiota and its potential use as a predictive immune biomarker in this disease

Might Oral Human Papillomavirus (HPV) Infection in Healthy Individuals Explain Differences in HPV-Attributable Fractions in Oropharyngeal Cancer? A Systematic Review and Meta-analysis

Background. Differences in oral human papillomavirus (HPV) prevalence and contrasts in HPV-attributable fractions (AFs) in oropharyngeal cancer (OPC) have not been evaluated in depth. Methods. A systematic review was performed to identify studies in which at least 50 healthy individuals were tested for oral HPV infection. Information on sex, age, tobacco/alcohol consumption, sex practices, specimen collection, HPV detection, and population type was extracted. Prevalences were pooled using random-effects models for meta-analyses of binomial data. Correlations were assessed by the Spearman test. Results. Forty-eight reports comprising 28 544 individuals fulfilled inclusion criteria. Global oral HPV prevalence was 4.9%. Estimates were highest in Europe, although regional differences were not statistically significant. HPV16 prevalence was 1.0% globally, and regional differences became statistically significant. A lifetime history of >6 sex partners showed a higher risk of oral HPV infection. The age-specific HPV distribution revealed a prevalence of >= 5% over 40 years of age and a lower prevalence at younger ages. There was no association between oral HPV prevalence and HPV-AFs or age-standardized rates (ASRs) of OPC, genital HPV in healthy women, or tobacco use. Conclusions. Differences in HPV-AFs or ASRs of OPC cannot be explained by differences in the prevalence of oral HPV infection across healthy populations. Consistent research on determinants of oral HPV prevalence, acquisition, clearance, and persistence is warranted

Potential impact of a nine-valent vaccine in human papillomavirus related cervical disease

Background: Information on human papillomavirus (HPV) type distribution is necessary to evaluate the potential impact of current and future HPV vaccines. We estimated the relative contribution (RC) to invasive cervical cancer (ICC) and precancerous cervical lesions of the nine HPV types (HPV 6/11/16/18/31/33/45/52/58) included in an HPV vaccine currently under development. Methods: Estimations on ICC were based on an international study of 8,977 HPV positive cases and estimations on precancerous cervical lesions were extracted from a published meta-analysis including 115,789 HPV positive women. Globocan 2008 and 2010 World Population Prospects were used to estimate current and future projections of new ICC cases. Results: RC of the 9 HPV types in ICC was 89.4%, with 18.5% of cases positive for HPV 31/33/45/52/58. Regional variations were observed. RCs varied by histology, ranging between 89.1% in squamous cell carcinomas (SCC) and 95.5% in adenocarcinomas (ADC). HPV 16/18/45 were detected in 94.2% of ADC. RC of the 9 types altogether decreased with age (trend test p < 0.0001), driven by the decrease in older ages of HPV 16/18/45. In contrast, the RC of HPV 31/33/52/58 increased with age. Due to population growth alone, projected estimates of ICC cases attributable to the 9 types are expected to rise from 493,770 new cases in 2012 to 560,887 new cases in 2025. The RCs of individual high risk HPV types varied by cytological and histological grades of HPV-positive precancerous cervical lesions, and there was an under representation of HPV 18 and 45 compared to ICC. Conclusions: The addition of HPV 31/33/45/52/58 to HPV types included in current vaccines could prevent almost 90% of ICC cases worldwide. If the nine-valent vaccine achieves the same degree of efficacy than previous vaccines, world incidence rates could be substantially reduced

Burden of Human papillomavirus (HPV)-related disease and potential impact of HPV vaccines in the Republic of Korea

Background: We aimed to review the burden and the potential impact of human papillomavirus (HPV) vaccines on HPV-related diseases in the Republic of Korea and to discuss cervical cancer prevention practices in this country. Methods: Cancer burden statistics were retrieved from GLOBOCAN-2018 and Statistics Korea. HPV disease burden was assessed via systematic review. Vaccine types relative contribution (RC) was estimated using data from an international project using formalin-fixed paraffin-embedded specimens. Results: Despite a downtrend in cervical cancer in recent years, Korean rates remain high. In contrast, oropharyngeal cancer incidence has gradually increased and other anogenital cancers remain rare. In Korea, HPV prevalence in general population is around 20%. In cervical cancer, RC of HPVs 16/18 (74.0%) increased to 92.0% when including HPVs 31/33/45/52/58. Limited information was available for other HPV-related cancer sites. Regarding prevention, since the inclusion of the HPV vaccine into the National Immunization Program, almost half (49%) of the target cohort in 2016 had received the first dose of vaccine. Further, percentage of women screened with pap has increased from 41.1%-2009 to 53.0%-2016. Conclusions: HPV-related disease burden in Korea is significant. Results suggest that the combination of effective and high coverage HPV vaccination and screening programmes could substantially impact on HPV-related disease in Korea

Competing mortality in oropharyngeal carcinoma according to HPV status

Purpose or Objective:The objective of the present study is to assess differences in the competing causes of death in oropharyngeal carcinoma (OPC) patients as a function of the HPV status

HPV16 variants distribution in invasive cancers of the cervix, vulva, vagina, penis, and anus

Human papillomavirus (HPV) 16 is the most oncogenic human papillomavirus, responsible for most papillomavirus-induced anogenital cancers. We have explored by sequencing and phylogenetic analysis the viral variant lineages present in 692 HPV16-monoinfected invasive anogenital cancers from Europe, Asia, and Central/South America. We have assessed the contribution of geography and anatomy to the differential prevalence of HPV16 variants and to the non-synonymous E6 T350G polymorphism. Most (68%) of the variance in the distribution of HPV16 variants was accounted for by the differential abundance of the different viral lineages. The most prevalent variant (above 70% prevalence) in all regions and in all locations was HPV16_A1-3, except in Asia, where HPV16_A4 predominated in anal cancers. The differential prevalence of variants as a function of geographical origin explained 9% of the variance, and the differential prevalence of variants as a function of anatomical location accounted for less than 3% of the variance. Despite containing similar repertoires of HPV16 variants, we confirm the worldwide trend of cervical cancers being diagnosed significantly earlier than other anogenital cancers (early fifties vs. early sixties). Frequencies for alleles in the HPV16 E6 T350G polymorphism were similar across anogenital cancers from the same geographical origin. Interestingly, anogenital cancers from Central/South America displayed higher 350G allele frequencies also within HPV16_A1-3 lineage compared with Europe. Our results demonstrate ample variation in HPV16 variants prevalence in anogenital cancers, which is partly explained by the geographical origin of the sample and only marginally explained by the anatomical location of the lesion, suggesting that tissue specialization is not essential evolutionary forces shaping HPV16 diversity in anogenital cancers

Human Papillomavirus Genotype Distribution in Invasive Cervical Cancer in Pakistan

Few studies have assessed the burden of human papillomavirus (HPV) infection in Pakistan. We aim to provide specific information on HPV-type distribution in invasive cervical cancer (ICC) in the country. A total of 280 formalin-fixed paraffin-embedded tissue blocks were consecutively selected from Shaukat Khanum Memorial Cancer Hospital and Research Centre (Lahore, Pakistan). HPV-DNA was detected by SPF10 broad-spectrum PCR followed by DNA enzyme immunoassay and genotyping by LiPA25. HPV-DNA prevalence was 87.5% (95%CI: 83.0-91.1), with 96.1% of cases histologically classified as squamous cell carcinoma. Most of the HPV-DNA positive cases presented single infections (95.9%). HPV16 was the most common type followed by HPV18 and 45. Among HPV-DNA positive, a significantly higher contribution of HPV16/18 was detected in Pakistan (78.4%; 72.7-83.3), compared to Asia (71.6%; 69.9-73.4) and worldwide (70.8%; 69.9-71.8) and a lower contribution of HPVs31/33/45/52/58 (11.1%; 7.9-15.7 vs. 19.8%; 18.3-21.3 and 18.5%; 17.7-19.3). HPV18 or HPV45 positive ICC cases were significantly younger than cases infected by HPV16 (mean age: 43.3, 44.4, 50.5 years, respectively). A routine cervical cancer screening and HPV vaccination program does not yet exist in Pakistan; however, the country could benefit from national integrated efforts for cervical cancer prevention and control. Calculated estimations based on our results show that current HPV vaccine could potentially prevent new ICC cases