Human papillomavirus is a necessary cause of invasive cervical cancer worldwide

Abstract

A recent report that 93 per cent of invasive cervical cancers worldwide contain human papillomavirus (HPV) may be an underestimate, due to sample inadequacy or integration events affecting the HPV L1 gene, which is the target of the polymerase chain reaction (PCR)‐based test which was used. The formerly HPV‐negative cases from this study have therefore been reanalysed for HPV serum antibodies and HPV DNA. Serology for HPV 16 VLPs, E6, and E7 antibodies was performed on 49 of the 66 cases which were HPV‐negative and a sample of 48 of the 866 cases which were HPV‐positive in the original study. Moreover, 55 of the 66 formerly HPV‐negative biopsies were also reanalysed by a sandwich procedure in which the outer sections in a series of sections are used for histological review, while the inner sections are assayed by three different HPV PCR assays targeting different open reading frames (ORFs). No significant difference was found in serology for HPV 16 proteins between the cases that were originally HPV PCR‐negative and ‐positive. Type‐specific E7 PCR for 14 high‐risk HPV types detected HPV DNA in 38 (69 per cent) of the 55 originally HPV‐negative and amplifiable specimens. The HPV types detected were 16, 18, 31, 33, 39, 45, 52, and 58. Two (4 per cent) additional cases were only HPV DNA‐positive by E1 and/or L1 consensus PCR. Histological analysis of the 55 specimens revealed that 21 were qualitatively inadequate. Only two of the 34 adequate samples were HPV‐negative on all PCR tests, as against 13 of the 21 that were inadequate ( p< 0·001). Combining the data from this and the previous study and excluding inadequate specimens, the worldwide HPV prevalence in cervical carcinomas is 99·7 per cent. The presence of HPV in virtually all cervical cancers implies the highest worldwide attributable fraction so far reported for a specific cause of any major human cancer. The extreme rarity of HPV‐negative cancers reinforces the rationale for HPV testing in addition to, or even instead of, cervical cytology in routine cervical screening. Copyright © 1999 John Wiley & Sons, Ltd.

Reduced rate of human papillomavirus infection and genetic overtransmission of TP53 72C polymorphic variant lower cervical cancer incidence

“…In agreement with results reported in a nearby country having comparable socioeconomic status,16 our results indicated that the prevalence of HPV infection of any genotypes in Saudi CxCa patients (77%) is below the estimated worldwide range (85%‐99%) 3, 4, 17. Statistical analysis revealed that this rate is significantly lower than the lowest (85%) global estimation (1 sample z‐test; 95% CI, 71% ‐ 82%; P  = .001).…”

“…However, its incidence is not uniform in various populations having different socioeconomic and national human development levels; a large majority of the global burden occurs in less‐developed regions, and the lowest rates are in western Asia 1. Infection with human papillomavirus (HPV) stands out as being the main cause among all known risk factors, and high‐risk HPVs drive the major carcinogenic events in the pathogenesis of CxCa, with an estimated worldwide prevalence ranging between 85% and 99% 2, 3, 4. In contrast, CxCa incidence is low in a few countries, even though they lack national screening programs 5.…”

INPP4B restrains cell proliferation and metastasis via regulation of the PI3K/AKT/SGK pathway

“…Although human papillomavirus (HPV) vaccines are available, cervical cancer still causes a considerable amount of death because of the limited application of the vaccine. Persistent infection with high‐risk HPV is the main aetiological factor in cervical carcinogenesis 2, 3, 4. However, HPV infection alone does not sufficiently explain the occurrence of cervical cancer because HPV oncogenes E6 and E7 can immortalize but do not transform human epithelial cells 5, 6.…”

Six‐year multi‐centre, observational, post‐marketing surveillance of the safety of the HPV‐16/18 AS04‐adjuvanted vaccine in women aged 10–25 years in Korea

“…In fact, 99.7% of CC cases worldwide showed the evidence of HPV infection 3. HPV‐16 and HPV‐18 are the most common HPV types detected in about 70% of global CC5 and 70.3% CC cases in Korea 2.…”