Human papillomavirus and tar hypothesis for squamous cell cervical cancer

Abstract

Human papillomavirus and tar hypothesis for squamous cell cervical cancerCervical cancer is the second most common life-threatening cancer among women worldwide, with incidence rates ranging from 4.8 per 100,000 in the Middle East to 44.3 per 100,000 in East Africa. Human papillomavirus (HPV) infection, especially HPV-16 and HPV-18, plays a major role in the etiology of cervical cancer, but HPV alone is not suffi cient to induce cancer. We propose that squamous cell cervical cancer is caused by an interaction of oncogenic viruses and cervical tar exposures. Cervical tar exposures occur from cigarette smoking, use of tar-based vaginal douche products (TBD), and long years of inhaling smoke from wood-and coal-burning stoves in poorly ventilated kitchens.

Human papillomavirus infection and cervical dysplasia in female sex workers in Northeast China: an observational study

“…Genital infection with human papillomavirus (HPV), particularly the high-risk subtypes HPV-16 and HPV-18, is playing a major role in the etiopathogenesis of cervical cancer [ 3 ]; although the virus alone may not be sufficient to cause cancer [ 4 ], virtually all cervical cancers are associated with persistent infection with one of the high-risk types of HPV.…”

Co-carcinogenesis: Human Papillomaviruses, Coal Tar Derivatives, and Squamous Cell Cervical Cancer

“…Epidemiologists working in Honduras associated cooking over wood-burning stoves and CC ( Ferrara et al, 2000 ; Velema et al, 2002 ). We pursued this link with another ecologic study and demonstrated that the Pearson coefficient for solid fuel use and CC was 0.498 ( p < 0.05) ( Bennett et al, 2010 ), further supporting a role for inhaling smoke from sources other than tobacco as a cofactor in CC development.…”

“…While HPV is a major factor for developing CC, and given that persistent infection with a high-risk “oncogenic” type of HPV appears to be necessary for the development of invasive CC ( Walboomers et al, 1999 ; Munoz et al, 2003 ), a number of studies have shown that squamous cell CC may result from an additive or synergistic interaction between oncogenic HPVs and cervical tar exposures, a process generally referred to as co-carcinogenesis ( Haverkos, 2004 ; Working Group on the Evaluation of Carcinogenic Risks to Humans [IARC], 2004 ; International Collaboration of Epidemiological Studies of Cervical Cancer [ICESCC] et al, 2006 ; International Collaboration of Epidemiological Studies of Cervical Cancer [ICESCC], 2007 ). We highlight coal tar derivatives from cigarette smoking, tar-based vaginal sanitization products, and inhaled smoke from burning biomass (wood, coal, dung) in poorly ventilated kitchens, as potential co-carcinogenic factors that contain bioactive compounds likely to play a determinative role in CC development ( Rotkin, 1967 ; Winkelstein, 1990 ; Ferrara et al, 2000 ; Haverkos et al, 2000 , 2003 ; Velema et al, 2002 ; Steckley et al, 2003 ; Working Group on the Evaluation of Carcinogenic Risks to Humans [IARC], 2004 ; Haverkos, 2005 ; International Collaboration of Epidemiological Studies of Cervical Cancer [ICESCC] et al, 2006 ; International Collaboration of Epidemiological Studies of Cervical Cancer [ICESCC], 2007 ; Bennett et al, 2010 ). We identify published data from virological and genetic studies linking oncogenic papillomavirus genotypes and chemicals to development of cancer ( Rous, 1965 ; Prokopczyk et al, 2009 ; Wei et al, 2014 ).…”

“…By 1970 manufacturers of those products voluntarily discontinued distribution of those products in the United States, but interestingly, not worldwide ( Kilmarx et al, 1998 ). We have proposed that those tar-based products placed directly on the cervix may produce similar changes as those due to cigarette smoking ( Bennett et al, 2010 ).…”

“…Although HPV infection is necessary for cervical cancer (CC) development, progression to cancer occurs in only a small percentage of HPV-infected women, and a number of studies have shown that incident cervicovaginal HPV is self-limited disease generally lasting less than a year in duration ( Ho et al, 1998 ; Woodman et al, 2001 ; Workowski et al, 2015 ). From our perspective, human papillomaviruses (HPVs) play a critical role in the etiology of CC, with several lines of epidemiologic and experimental evidence supporting a role for non-viral (co-carcinogens) in controlling the risk for progression to neoplasia among HPV-infected individuals ( Bennett et al, 2010 ; Wei et al, 2014 ; Goodson et al, 2015 ). The studies cited here were identified from a systemic review we conducted ( Haverkos et al, 2003 ), reviews conducted by others ( Working Group on the Evaluation of Carcinogenic Risks to Humans [IARC], 2004 ; International Collaboration of Epidemiological Studies of Cervical Cancer [ICESCC] et al, 2006 ; International Collaboration of Epidemiological Studies of Cervical Cancer [ICESCC], 2007 ), and other papers that we have read.…”