HPV73 a nonvaccine type causes cervical cancer

Abstract

HPV73 is classified as possibly oncogenic. It is neither routinely evaluated in HPV screening, nor covered by any of the prophylactic vaccines. We sought to investigate the carcinogenic characteristics of HPV73. Molecular studies were performed on eight cervix cancer biopsy specimens containing HPV73 from a cross‐sectional cancer cohort of 590 women referred to the National Cancer Institute in Rio de Janeiro, Brazil. Transcriptional activity of HPV73 was evaluated by detection of spliced transcripts of E6/E6* and E1^E4 in cDNA created from RNA isolated from fresh tissue. Disruption of viral E1 and E2 genes in the tumor DNA was assessed by overlapping PCR amplification. Evaluation of viral integration was performed using a customized capture panel and next‐generation sequencing, and an in‐house bioinformatic pipeline. HPV73 E6/E6* transcripts were found in 7/7 specimens with available RNA, and three also had HPV73 E1^E4 transcripts. Disruption of E1 and E2 genes was observed in 4/8 specimens. Integration of HPV73 sequences into the cancer cell genomes was identified in all cervix cancer tissues. These results provide evidence that HPV73 is an oncogenic virus that can cause invasive cervix cancer. With current molecular screening and HPV vaccination, not all cervix cancers will be prevented.

The prevalence of VAIN, CIN, and related HPV genotypes in Japanese women with abnormal cytology

“…HPV73 was previously thought to be a LR type, but a recent report suggested that it can be identified in cervical cancer . Compared with the prevalence in CIN, HPV53 and HPV73 were more frequent in VAIN than in CIN in the present study (Figure C).…”

Long‐term follow‐up of human papillomavirus type replacement among young pregnant Finnish females before and after a community‐randomised HPV vaccination trial with moderate coverage

“…Nevertheless, this finding of a possible HPV 6 herd effect postbivalent HPV vaccination, is consistent with previous findings of bivalent vaccine efficacy against HPV6, 36 reported postvaccine era reductions in genital warts when using the bivalent vaccine, 37,38 and also with findings of HPV6 specific vaccine-induced cross-neutralising antibodies among individuals vaccinated with the bivalent HPV vaccine. 35 39 HPV73 is from the alpha 11 species group, which is of particular interest given that the alpha 11 species group is phylogenetically close to the alpha 9 species, and the degree of cross-protection is correlated to the phylogenetic distance to the vaccine types. 40 Contrary to this, the observed decrease of HPV66 in Arm A was unexpected.…”

“…2 Since 2007, these vaccines have been gradually implemented in national vaccination programs. 3 However, there are a total of 12 high-risk HPV types which are classified by the International Agency for Research on Cancer (IARC) as carcinogenic to humans, HPV16, 18,31,33,35,39,45,51,52, 56, 58 and 59, with a further eight types classified as possibly (or probably) carcinogenic, HPV26, 53, 66, 68, 67, 70, 73 and 83. 4 As such, concern has been flagged over a decade ago, whether such selective vaccination could induce HPV type replacement to occur.…”

“…27 Birth cohort-specific vaccination coverages for males and females by community and calendar year were gathered from the Finnish vaccination register. 22,262.2 | Laboratory analysesThe retrieved FMC serum samples were analysed for the presence of serum antibodies to HPV6,11,16,18,31,33,35,39,45, 51, 52, 56, 58, 59, 66, 68, 73 and herpes simplex virus type II (HSV-2) using heparin bound HPV pseudovirion and HSV-2 glycoprotein G 2 Luminex assay 22,28,29. A negative control panel of serum samples from children under the age of 12-years-old was used to calculate HPV type-specific seropositivity cut-off values, by computing the median fluorescence intensities of the negative control serum panel plus three…”

Human Papillomavirus (HPV69/HPV73) Coinfection associated with Simultaneous Squamous Cell Carcinoma of the Anus and Presumed Lung Metastasis

“…At present, there is limited epidemiological data on the occurrence of HPV69 and HPV73 worldwide. This phenomenon may be explained by regional variability in the prevalence of HPV oncogenic types [15], as well as by variable performance of current detection and typing methods, which are generally designed to screen for the most common high-risk human-associated HPV genotypes [1].…”