The Impact of Human Immunodeficiency Virus and Human Papillomavirus Co-Infection on HPV Genotype Distribution and Cervical Lesion Grade in a Semi-Urban Population in Tigoni, Kenya

Abstract

1. IntroductionCervical cancer is an important global public healthproblem and a common cause of death among women,and it is attributable to human papillomavirus (HPV)(Walboomers et al, 1999; Parkin et al, 2008). In a largeseries of invasive cervical cancer from around theworld, HPV-DNA was detected in 99.7% of the tumors,leading to the conclusion that HPV was a necessarycause of cervical cancer (Bosch et al, 1995; Walboomerset al, 1999; Bosch et al, 2007). The identification ofHPV’s role in cervical cancer has led to importantadvances in primary prevention through vaccinationand diagnosis through HPV detection (Stanley et al,2008; Bosch et al, 2008). However, tangible reductionin the incidence of cervical cancer and the impact onglobal public health will probably take decades. As HPVtypes are divergent, efficacy of current vaccines is typerestricted,and therefore development of the nextgeneration of HPV vaccines will require inclusion ofrelevant antigens from several HPV types (Lowy, 2008).Geographical profiling of HPV type distribution will beimportant in making vaccines more relevant for targetpopulations.Most women will be infected with HPV sometime intheir lifetime. Results from large meta-analyses studiesindicate that at any given point in time, 10.4% (95%confidence interval (CI) 10.2-10.7) of womenworldwide are positive for cervical HPV DNA (Bosch etal, 2008). The prevalence of HPV is higher in lessdeveloped regions (13.4%; 95% CI: 13.1-13.7) than inthe more developed regions (8.4%; 95% CI: 8.3-8.6)(Bosch et al, 2008). The same studies indicate thatAfrican women at 22.1% (95% CI: 20.9-23.4) and EastAfrican women in particular, have the highest HPVprevalence rates (31.6%; 95% CI: 29.5-33.8) (Bosch etal, 2008). HPV type 16 is the most common in allcontinents, with an estimated point prevalence of 2.6%(95% CI: 2.5-2.8) worldwide, and HPV type 18 thesecond most frequently detected type (Clifford et al,2005). Regional differences are thought to be related togeographical and immunogenetic factors, such asdefects in cellular immunity through chronic cervicalinflammation, malnutrition and more recently, HIVinfection; Type 16 though appears to be less influencedby immune impairment than other types (Clifford et al,2005).Although many women get infected with HPV, most donot develop cervical cancer. Several co-factors arepostulated to influence the disease process. Thepotential co-factors include exogenous factors such astobacco smoking, hormonal contraceptives, and coinfectionswith other sexually transmitted infections(Munoz et al, 2006). In addition, viral co-factors, suchspecific HPV types, viral load, and viral integration, aswell as host co-factors such as endogenous hormones,genetic factors, and factors related to the immuneresponse may variably influence the course of HPVinfection (Munoz et al, 2006).Women with HIV infection have been shown to be morelikely not only to have a concurrent HPV infection butalso to have an increased risk for a high grade cervicalsquamous intraepithelial lesion (La Ruche et al, 1998;Temmerman et al, 1999; Womack et al, 2000; Baay et al,2004; Hawes et al, 2006; Didelot-Rousseau et al, 2006;Ngándwe et al, 2007). HPV is the commonest sexuallytransmitted infection, with more than 75% of sexuallyactive adults acquiring one or more genotypes in theirlifetime (Bosch et al, 2008). However, by age 30 years,most women clear the infection due to an effective cellmediatedimmune response, and only a small numberthereafter are diagnosed with a HPV-associated lesion(Schiffman, 1992). It is thought that it is through itseffect on CD4+ cells and regulation of immuneresponses to a variety of antigens that HIV attenuatesthe systemic response to HPV (Palefsky, 2006).The prevalence of HIV among adult Kenyan women was13% in 2003 with trends reported to have decreased to5.1% by 2006 (KDHS, 2003). The high prevalence ofHIV may increase the incidence of cervical pre-cancerand potentially, of cervical cancer. Gichangi et al (2002),however, demonstrated that a two to three-foldincrease in HIV prevalence did not translate to aproportionate increment in incidence of cervical cancer.They hypothesized that HIV-infected women die fromHIV-related opportunistic infections before theydevelop invasive cervical cancer. The mean survivaltime for women with HIV in 2008 was reported to be 5years (Yamada et al, 2008) while typically more than 10years elapse before the development of cervical cancerafter HPV infection. Yamada et al (2008) also advancedthe possibility that sub-clinical cervical cancer may bemissed in many women dying prematurely from AIDSrelatedopportunistic infections.This study was carried out to establish whether the coinfectionof HIV and HPV has an influence on HPVgenotype distribution and on the prevalence and gradeof cervical neoplasia