If carcinogenesis occurs by somatic evolution, then common components of the cancer phenotype result from active selection and must, therefore, confer a significant growth advantage. A near-universal property of primary and metastatic cancers is upregulation of glycolysis, resulting in increased glucose consumption, which can be observed with clinical tumour imaging. We propose that persistent metabolism of glucose to lactate even in aerobic conditions is an adaptation to intermittent hypoxia in pre-malignant lesions. However, upregulation of glycolysis leads to microenvironmental acidosis requiring evolution to phenotypes resistant to acid-induced cell toxicity. Subsequent cell populations with upregulated glycolysis and acid resistance have a powerful growth advantage, which promotes unconstrained proliferation and invasion.

Why do cancers have high aerobic glycolysis

The causal role of human papillomavirus infections in cervical cancer has been documented beyond reasonable doubt. The association is present in virtually all cervical cancer cases worldwide. It is the right time for medical societies and public health regulators to consider this evidence and to define its preventive and clinical implications. A comprehensive review of key studies and results is presented.

https://jcp.bmj.com/content/jclinpath/55/4/244.full.pdf

The causal relation between human papillomavirus and cervical cancer

비만아 부모의 돌봄 경험: q 방법론

Background: High-risk human papillomaviruses (HPVs) are etiologic agents for anogenital tract cancers and have been detected in head and neck squamous cell carcinomas (HNSCCs). We investigated, retrospectively, an etiologic role for HPVs in a large series of patients with HNSCC. Methods: Tumor tissues from 253 patients with newly diagnosed or recurrent HNSCC were tested for the presence of HPV genome by use of polymerase chain reaction (PCR)-based assays, Southern blot hybridization, and in situ hybridization. The viral E6 coding region was sequenced to confirm the presence of tumor-specific viral isolates. Exons 5‐9 of the TP53 gene were sequenced from 166 specimens. The hazard of death from HNSCC in patients with and without HPVpositive tumors was determined by proportional hazards regression analysis. Results: HPV was detected in 62 (25%) of 253 cases (95% confidence interval [CI] = 19%‐30%). Highrisk, tumorigenic type HPV16 was identified in 90% of the HPV-positive tumors. HPV16 was localized specifically by in situ hybridization within the nuclei of cancer cells in preinvasive, invasive, and lymph node disease. Southern blot hybridization patterns were consistent with viral integration. Poor tumor grade (odds ratio [OR] = 2.4; 95% CI = 1.2‐ 4.9) and oropharyngeal site (OR = 6.2; 95% CI = 3.1‐12.1) independently increased the probability of HPV presence. As compared with HPV-negative oropharyngeal cancers, HPVpositive oropharyngeal cancers were less likely to occur among moderate to heavy drinkers (OR = 0.17; 95% CI = 0.05‐0.61) and smokers (OR = 0.16; 95% CI = 0.02‐1.4), had a characteristic basaloid morphology (OR = 18.7; 95% CI = 2.1‐167), were less likely to have TP53 mutations (OR = 0.06; 95% CI = 0.01‐0.36), and had improved disease-specific survival (hazard ratio [HR] = 0.26; 95% CI = 0.07‐0.98). After adjustment for the presence of lymph node disease (HR = 2.3; 95% CI = 1.4‐ 3.8), heavy alcohol consumption (HR = 2.6; 95% CI = 1.4‐4.7), and age greater than 60 years old (HR = 1.4; 95% CI = 0.8‐2.3), all patients with HPV-positive tumors had a 59% reduction in risk of death from cancer when compared with HPV-negative HNSCC patients (HR = 0.41; 95% CI = 0.20‐0.88). Conclusions: These data extend recent molecular and epidemiologic studies and strongly suggest that HPV-positive oropharyngeal cancers comprise a distinct molecular, clinical, and pathologic disease entity that is likely causally associated with HPV infection and that has a markedly improved prognosis. [J Natl Cancer Inst 2000; 92:709‐20]

Evidence for a Causal Association Between Human Papillomavirus and a Subset of Head and Neck Cancers

Epstein-Barr virus.

Prevalence of Novel Gamma Hpv Types 223 and 225 in Oral Cavity and Skin of Indian Normal and Neoplastic Participants

The aim of our study was to evaluate the prevalence of different HPV genera—alpha, beta and gamma—in Juvenile onset Recurrent Respiratory Papillomatosis (JoRRP) and examine the association of type and genus-specific viral features with the clinical outcome of disease. This retrospective observational study included consecutive patients with JoRRP who were treated in a referral centre between October 2000 and October 2020. All patients underwent cold excision and laser vaporisation of papillomatous lesions. Samples were analysed for the presence of 120 viral genotypes (22 alpha-HPV, 46 beta-HPV, 52 gamma-HPV) using a highly sensitive multiplex genotyping assay. Twenty patients with JoRRP, aged 0.3–11 years, were included, with a median follow-up of 13.5 years. All samples were HPV DNA positive: 20 (100%) for alpha-HPV DNA; 7 (35%) for beta—HPV DNA; 0 for gamma-HPV DNA. Three groups were defined according to the number of infections: seven cases (35%) with HPV mono-infection; ten cases (50%) with HPV double-infection; three cases (15%) with ≥ 3 HPV infections. At diagnosis, patients with ≥ 3 HPV infections reported higher median Derkay’s score than those with mono-infection (21 vs 14, P = 0.018). Number of HPV infections was also associated with clinical outcomes, with an average of 0.5 surgical procedures/year in patients with mono-infection, 1.2 for double-infection, 2.6 for ≥ 3 infections (P = 0.006). Despite the small sample size, these preliminary data support an association between the number of different alpha and beta HPV co-infections and the clinical severity of the disease.

/pdf/clinical-implications-of-alpha-beta-and-gamma-hpv-infection-1xus6fm9b2.pdf

Clinical implications of alpha, beta, and gamma HPV infection in juvenile onset recurrent respiratory papillomatosis.

Delivery andExpression ofa Heterologous Antigen on theSurface ofStreptococci

Human papillomavirus (HPV) plays an essential role in cervical cancer development. Angola has a high cervical cancer incidence rate (36.1 per 100,000); therefore, knowledge of HPV among clinicians is essential for the prevention of cervical cancer and educating at-risk individuals. This study aimed to evaluate knowledge of HPV among healthcare professionals in Angola. A 44-item questionnaire was distributed to 65 healthcare professionals who attended a conference on the cancer burden in Angola. Non-parametric and multiple regression analyses were conducted. Of the participants (55.6%) were male, and 33.3% were aged 31-40 years, 56.3% had an undergraduate degree, and 35.9% had a postgraduate degree. All participants worked in healthcare in academic and/or clinical settings, with 36.7% in joint contracts. Most (62.2%) knew that early sexual debut increases the risk of contracting HPV, and HPV vaccines are most effective if administered before sexual debut. However, there was limited knowledge regarding the virus transmission. The mean HPV knowledge score was 11.08 ± 8.76 and knowledge was higher among older healthcare workers (>50 years) with a postgraduate degree and working in a clinical role. Overall, HPV knowledge was limited among the respondents. Policymakers should consider promoting knowledge and targeted public health initiatives among healthcare professionals in Angola.

Evaluation of human papillomavirus (HPV) knowledge among healthcare professionals: A study of conference attendees in Angola.

We report the genetic characterization of a new papillomavirus (HPV_MTS1) isolated and fully cloned from a skin swab. The L1 open reading frame of HPV_MTS1 was 85% identical to its closest human papillomavirus (HPV) type 80, which belongs to the species beta-2 of the genus Betapapillomavirus, hence qualifying it as a new HPV type.

Massimo Tommasino

Papers

Prevalence of Novel Gamma Hpv Types 223 and 225 in Oral Cavity and Skin of Indian Normal and Neoplastic Participants

Clinical implications of alpha, beta, and gamma HPV infection in juvenile onset recurrent respiratory papillomatosis.

Delivery andExpression ofa Heterologous Antigen on theSurface ofStreptococci

Evaluation of human papillomavirus (HPV) knowledge among healthcare professionals: A study of conference attendees in Angola.

Complete Genome Sequence of a Novel Human Betapapillomavirus Isolated from a Skin Sample