Epidemiology of HPV genotypes in Uganda and the role of the current preventive vaccines: A systematic review

Background

Limited data are available on the distribution of human papillomavirus (HPV) genotypes in the general population and in invasive cervical cancer (ICC) in Uganda. Yet, with the advent of preventive HPV vaccines that target HPV 16 and 18 responsible for causing about 70% of ICC cases in the world, such information is crucial to predict how vaccination and HPV-based screening will influence prevention of ICC.

Methods

To review the distribution of HPV infection and prevalent genotypes, electronic databases (e.g. PubMed/MEDLINE and HINARI) were searched for peer reviewed English articles on HPV infection up to November 30, 2010. Eligible studies were selected according to the following criteria: DNA-confirmed cervical or male genital HPV prevalence and genotypes, HPV incidence estimates and HPV seroprevalence among participants.

Results

Twenty studies were included in the review. Among HIV negative adult women, the prevalence of HR-HPV infections ranged from 10.2% -40.0% compared to 37.0% -100.0% among HIV positive women. Among HIV positive young women aged below 25 years, the prevalence of HR-HPV genotypes ranged from 41.6% -75.0% compared to 23.7% -67.1% among HIV negative women. Multiple infections with non vaccine HR-HPV genotypes were frequent in both HIV positive and HIV negative women. The main risk factors for prevalent HPV infections were age, lifetime number of sexual partners and HIV infection. Incident infections with HR-HPV genotypes were more frequent among adult HIV positive than HIV negative women estimated at 17.3 and 7.0 per 100 person-years, respectively. Similarly, incident HR-HPV among young women aged below 25 years were more frequent among HIV positive (40.0 per 100 person-years) than HIV negative women (20.3 per 100 person-years) women. The main risk factor for incident infection was HIV infection. HPV 16 and 18 were the most common genotypes in ICC with HPV 16/18 contributing up to 73.5% of cases with single infections. Among uncircumcised adult HIV positive males, HR-HPV prevalence ranged from 55.3% -76.6% compared to 38.6% -47.6% in HIV negative males. Incident and multiple HR-HPV infections were frequent in HIV positive males. Being uncircumcised was the main risk factor for both prevalent and incident HPV infection.

Conclusion

Infections with HR-HPV genotypes were very common particularly among HIV positive individuals and young women irrespective of HIV status. Given the high prevalence of HIV infection, HPV-associated conditions represent a major public health burden in Uganda. However, although the most common HPV genotypes in ICC cases in Uganda were those targeted by current preventive vaccines, there were a large number of individuals infected with other HR-HPV genotypes. Technology allowing, these other HR-HPV types should be considered in the development of the next generation of vaccines.     

Human papillomavirus and risk factors for cervical cancer in Chennai,India: a case-control study

To evaluate the role of human papillomavirus (HPV) and other risk factors in the aetiology of invasive cervical carcinoma (ICC), we conducted a hospital-based case-control study in Chennai, Southern India. A total of 205 ICC cases (including 12 adenocarcinomas) and 213 frequency age-matched control women were included. HPV DNA in cervical cells was evaluated by means of a polymerase chain-reaction assay. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were computed by means of unconditional multiple logistic regression models. HPV infection was detected in all but one ICC cases and in 27.7% of control women (OR = 498). Twenty-three different HPV types were found. HPV 16 was the most common type in either cases or controls, followed by HPV 18 and 33. The association of ICC with HPV 18 and HPV 16-associated types was somewhat stronger than the one with HPV 16. Multiple HPV infections did not show a higher OR for ICC than single infections. Other than HPV infection, high parity (OR for >4 vs. /=45 years = 4.2) were significantly associated with ICC, also after restricting the analysis to HPV-positive cases and controls. Poor hygienic conditions were associated with an increased risk of HPV infection among control women but not with ICC risk among HPV-positive women. A vaccine against HPV 16 and 18 may be effective in more than three-quarters of ICC in the study area.     

Variability of high risk HPV genotypes among HIV infected women in Mwanza,Tanzania- the need for evaluation of current vaccine effectiveness in developing countries

Background

High risk (HR) human papilloma Virus (HPV) genotypes have been associated with cervical cancer. In Tanzania there is a limited data on the epidemiology of HPV and genotypes distribution among HIV infected women. Here we document varieties of HPV genotypes associated with cervical squamous intraepithelial lesions (SIL) among HIV- infected women at Bugando Medical Centre, Mwanza-Tanzania.

Methods

A cross sectional hospital based study involving HIV infected women was conducted between August and October, 2014. Exfoliated cells from ectocervix and endocervix were collected using cytobrush. HPV genotypes were detected using polymerase chain reaction (PCR) followed by sequencing using specific primers targeting broad range of HPV types. Cytology was done to establish squamous intraepithelial lesions. Log binomial regression analysis was done to establish risk ratios (RR) associated with HPV infection using STATA version 11.

Results

A total of 255 HIV infected women with mean age 39.2?±?9.1 years were enrolled in the study. HPV DNA was detected in 138/255 (54.1 %, 95 % CI: 47-60) of HIV infected women. Twenty six genotypes were detected in various combinations; of these 17(65.3 %) were of HR genotypes. HR genotypes were detected in 124(48.6 %) of HIV infected women. Common HR genotypes detected were HPV-52(26), HPV-58(21), HPV-35(20) and HPV-16(14). The risk of being HPV positive was significantly higher among women with CD4 counts <100 (RR: 1.20, 95 % CI: 1.05-1.35, P?=?0.006) and women with SIL (RR: 1.37, 95 % CI: 1.11-1.68, P?=?0.005)

Conclusion

Significant proportion of HIV infected women with low CD4 counts have various grades of cervical SIL associated with varieties of uncommon HR genotypes. There is a need to evaluate the effectiveness of the current vaccine in preventing cervical cancer in developing countries where HIV is endemic.

     

Incidence of cervical disease associated to HPV in human immunodeficiency infected women under highly active antiretroviral therapy

Background  

Women infected with human immunodeficiency virus (HIV) may be at higher risk of developing cervical cancer than non infected women. In a pilot study, we assessed the relationships among cervical cytology abnormalities associated to Human Papillomavirus (HPV), HIV infection and Highly Active Antiretroviral Therapy (HAART) on the development of Squamous Intraepithelial lesions (SILs). Out of the 70 HIV infected women from Douala -Cameroon (Central Africa) that we included in the study, half (35) were under HAART. After obtaining information related to their lifestyle and sexual behaviour, cervicovaginal samples for Pap smears and venous blood for CD4 count were collected and further divided into two groups based upon the presence or absence of cervical cytology abnormalities i.e. those with normal cervical cytology and those with low and high Squamous Intraepithelial lesions (LSIL, HSIL).     

Increased risk for cervical disease progression of French women infected with the human papillomavirus type 16 E6-350G variant.

To test the significance of human papillomavirus (HPV) type 16 and HPV16 E6 variants as risk factors for viral persistence and progression to high-grade lesion, we did a nested case-control study within a cohort study of >15,000 Caucasian French women. Three groups infected with high-risk HPV were compared: (a) women with cleared infection (controls, n = 201), (b) women with persistent infection (cases, n = 87), and (c) women who progressed into high-grade lesion (cases, n = 58). Women with persistent HPV infection and those that progressed into high-grade lesions were likelier to harbor HPV16 than other high-risk HPV types [odds ratio (OR), 2.4; 95% confidence interval (95% CI), 1.3-4.3 and OR, 4.2; 95% CI, 2.2-8.1, respectively]. Notably, especially elevated ORs of persistence (3.0; 95% CI, 1.4-6.7) and progression (6.2; 95% CI, 2.7-14.3) were found among women who harbored the HPV16 350G variant. Thus, HPV type and HPV16 variant seem to be risk factors for viral persistence and progression of infections into high-grade cervical lesions.     

Prevalence of human papillomavirus in women with invasive cervical carcinoma by HIV status in Kenya and South Africa

Data on the prevalence of human papillomavirus (HPV) types in cervical carcinoma in women with HIV are scarce but are essential to elucidate the influence of immunity on the carcinogenicity of different HPV types, and the potential impact of prophylactic HPV vaccines in populations with high HIV prevalence. We conducted a multicentre case-case study in Kenya and South Africa. During 2007-2009, frozen tissue biopsies from women with cervical carcinoma were tested for HPV DNA using GP5+/6+-PCR assay. One hundred and six HIV-positive (mean age 40.8 years) and 129 HIV-negative women (mean age 45.7) with squamous cell carcinoma were included. Among HIV-positive women, the mean CD4 count was 334 cells/μL and 48.1% were on combined antiretroviral therapy. HIV-positive women had many more multiple HPV infections (21.6% of HPV-positive carcinomas) compared with HIV-negative women (3.3%) (p < 0.001) and the proportion of multiple infections was inversely related to CD4 level. An excess of HPV18 of borderline statistical significance was found in HIV-positive compared with HIV-negative cases (Prevalence ratio (PR) = 1.9, 95% confidence interval (CI): 1.0-3.7, adjusted for study centre, age and multiplicity of infection). HPV16 and/or 18 prevalence combined, however, was similar in HIV-positive (66.7%) and HIV-negative cases (69.1%) (PR = 1.0, 95% CI: 0.9-1.2). No significant difference was found for other HPV types. Our data suggest that current prophylactic HPV vaccines against HPV16 and 18 may prevent similar proportions of cervical SCC in HIV-positive as in HIV-negative women provided that vaccine-related protection is sustained after HIV infection.     

Human papillomavirus infections with multiple types and risk of cervical neoplasia.

BACKGROUND: Besides an established role for certain human papillomavirus (HPV) genotypes in the etiology of cervical cancer, little is known about the influence of multiple-type HPV infections on cervical lesion risk. We studied the association between multiple HPV types and cervical lesions among 2,462 Brazilian women participating in the Ludwig-McGill study group investigation of the natural history of HPVs and cervical neoplasia. METHODS: Cervical specimens were typed by a PCR protocol. The cohort's repeated-measurement design permitted the assessment of the relation between the cumulative and concurrent number of HPV types and any-grade squamous intraepithelial lesions (SIL) and high-grade SIL (HSIL). RESULT: At individual visits, 1.9% to 3.2% of the women were infected with multiple HPVs. Cumulatively during the first year and the first 4 years of follow-up, 12.3% and 22.3% were infected with multiple types, respectively. HSIL risk markedly increased with the number of types [odds ratio (OR), 41.5; 95% confidence interval (95% CI), 5.3-323.2 for single-type infections; OR, 91.7; 95% CI, 11.6-728.1 for two to three types; and OR, 424.0; 95% CI, 31.8-5651.8 for four to six types, relative to women consistently HPV-negative during the first year of follow-up]. The excess risks for multiple-type infections remained after exclusion of women infected with HPV-16, with high-risk HPV types, or persistent infections, particularly for any-grade SIL. Coinfections involving HPV-16 and HPV-58 seemed particularly prone to increase risk. CONCLUSION: Infections with multiple HPV types seem to act synergistically in cervical carcinogenesis. These findings have implications for the management of cervical lesions and prediction of the outcome of HPV infections.     

Human papillomavirus prevalence and type distribution in invasive cervical cancer in sub‐Saharan Africa

In sub‐Saharan Africa, invasive cervical cancer (ICC) incidence and mortality are among the highest in the world. This cross‐sectional epidemiological study assessed human papillomavirus (HPV) prevalence and type distribution in women with ICC in Ghana, Nigeria, and South Africa. Cervical biopsy specimens were obtained from women aged ≥21 years with lesions clinically suggestive of ICC. Histopathological diagnosis of ICC was determined by light microscopy examination of hematoxylin and eosin stained sections of paraffin‐embedded cervical specimens; samples with a confirmed histopathological diagnosis underwent HPV DNA testing by polymerase chain reaction. HPV‐positive specimens were typed by reverse hybridization line probe assay. Between October 2007 and March 2010, cervical specimens from 659 women were collected (167 in Ghana, 192 in Nigeria and 300 in South Africa); 570 cases were histologically confirmed as ICC. The tumor type was identified in 551/570 women with ICC; squamous cell carcinoma was observed in 476/570 (83.5%) cases. The HPV‐positivity rate in ICC cases was 90.4% (515/570). In ICC cases with single HPV infection (447/515 [86.8%]), the most commonly detected HPV types were HPV16 (51.2%), HPV18 (17.2%), HPV35 (8.7%), HPV45 (7.4%), HPV33 (4.0%) and HPV52 (2.2%). The prevalence of single and multiple HPV infections seemed higher among HIV‐positive women and HPV type distribution appeared to differ according to tumor type and HIV status. In conclusion, HPV16, 18, 45 and 35 were the most common HPV types in sub‐Saharan African women with ICC and HPV infections were more common in HIV‐positive women.     

Human papillomavirus and human immunodeficiency virus infections: relation with cervical dysplasia-neoplasia in African women

Our study assessed the factors associated with cervical squamous intra-epithelial lesions (SILs) and invasive cervical cancer, with special attention to human immunodeficiency virus (HIV) and human papillomavirus (HPV) infections. Women from 3 outpatient gynecology clinics of Abidjan, Côte d'Ivoire, were screened for cervical abnormalities: 151 women with low-grade SILs and 151 controls, 60 with high-grade SILs and 240 controls, and 13 with invasive cancer and 65 controls were enrolled in 3 case-control studies. Controls were chosen at random among the women without lesions, with a frequency matching for age and center. We used the PCR method for the detection of cervical HPV DNA and the restriction fragment length polymorphism analysis for HPV typing. HIV antibody testing and CD4 cell count were performed. In multivariate analyses, factors associated with cervical lesions were: for low-grade SILs, HPV positivity, HIV-1 seropositivity and parity >3; for high-grade SILs, HPV positivity, chewing tobacco, HIV-1 seropositivity and illiteracy, and for invasive cancer, HPV positivity only. We found a diversity of HPV types associated with SILs. In HIV-1-infected women, SILs occurred at an early stage of HIV disease. Women infected with both HIV-1 and HPV were at much higher risk of SILs than women infected with each of these 2 viruses separately. Invasive cancer was linked to HIV-2 infection in univariate analysis only. Our results suggest that the relation of SILs with HIV-1 infection is mainly explained by HPV infection and that HIV-1-infected African women may not often reach the invasive stage of cervical cancer. Int. J. Cancer 76:480–486, 1998.© 1998 Wiley-Liss, Inc.     

Polymorphisms in codon 31 of p21 and cervical cancer susceptibility in Korean women

The aim of this study was to determine whether the codon 31 genotype of p21 might be associated with an increased risk of cervical cancer development in Korean women. We used tissue derived from patients with invasive cervical cancer (ICC) (n=111, composed of two histologic groups: squamous cell carcinoma (n=67) and adenocarcinoma (n=44)), cervical intraepithelial neoplasia (CIN) III (n=101), and non-cancer controls (NCC, n=98). For the determination of p21 polymorphism, genomic DNA was examined by polymerase chain reaction-restriction fragment length polymorphism assay using BsmAI. We compared the distribution of the p21 genotype in ICC, CIN III, and control and also analyzed the association of this polymorphism with the risk of development of cervical cancer, especially in patients with high-risk human papillomavirus (HPV) (16 or 18)-positive cervical cancer. A significant increase of Ser/Ser genotype frequency was found in adenocarcinoma patients with high-risk HPV (16 or 18) compared with the NCC group (P=0.009). The odds ratio was 3.59 (95% CI 1.55-8.31) when comparing adenocarcinoma patients associated with high-risk HPV with NCC. We found that the codon 31 Ser/Ser homozygote of the p21 gene could be a risk factor for the development of cervical adenocarcinoma associated with high-risk HPV.     

Time to clearance of human papillomavirus infection by type and human immunodeficiency virus serostatus

Persistent infection with high-risk human papillomavirus (HPV) is central to cervical carcinogenesis. Certain high-risk types, such as HPV16, may be more persistent than other HPV types, and type-specific HPV persistence may differ by HIV serostatus. This study evaluated the association between HPV type and clearance of HPV infections in 522 HIV-seropositive and 279 HIV-seronegative participants in the HIV Epidemiology Research Study (HERS, United States, 1993-2000). Type-specific HPV infections were detected using MY09/MY11/HMB01-based PCR and 26 HPV type-specific probes. The estimated duration of type-specific infections was measured from the first HPV-positive visit to the first of two consecutive negative visits. Hazard ratios (HRs) and 95% confidence intervals (CIs) for HPV clearance were calculated using Cox models adjusted for study site and risk behavior (sexual or injection drugs). A total of 1,800 HPV infections were detected in 801 women with 4.4 years median follow-up. HRs for clearance of HPV16 and related types versus low-risk HPV types were 0.79 (95% CI: 0.64-0.97) in HIV-positive women and 0.86 (95% CI: 0.59-1.27) in HIV-negative women. HRs for HPV18 versus low-risk types were 0.80 (95% CI: 0.56-1.16) and 0.57 (95% CI: 0.22-1.45) for HIV-positive and -negative women, respectively. HPV types within the high-risk category had low estimated clearance rates relative to low-risk types, but HRs were not substantially modified by HIV serostatus.     

HPV infection in women with and without cervical cancer in Conakry, Guinea

Background:

Cervical cancer incidence in western Africa is among the highest in the world.

Methods:

To investigate human papillomavirus (HPV) infection in Guinea, we obtained cervical specimens from 831 women aged 18–64 years from the general population of the capital Conakry and from 77 locally diagnosed invasive cervical cancers (ICC). Human papillomavirus was detected using a GP5+/6+ PCR-based assay.

Results:

Among the general population, the prevalence of cervical abnormalities was 2.6% by visual inspection and 9.5% by liquid-based cytology. Fourteen of 15 high-grade squamous intraepithelial lesions were visual inspection-negative. Human papillomavirus prevalence was 50.8% (32.1% for high-risk types) and relatively constant across all age groups. Being single or reporting ⩾3 sexual partners was significantly associated with HPV positivity. HPV16 was the most common type, both among the general population (7.3%) and, notably in ICC (48.6%). HPV45 (18.6%) and HPV18 (14.3%), the next most common types in ICC, were also more common in ICC than in HPV-positive women with normal cytology from the general population.

Conclusion:

The heavy burden of HPV infection and severe cervical lesions in Guinean women calls for new effective interventions. Sixty-three per cent of cervical cancers are theoretically preventable by HPV16/18 vaccines in Guinea; perhaps more if some cross-protection exists with HPV45.     

Human papillomavirus type-distribution in cervical cancer in China: the importance of HPV 16 and 18

Prophylactic vaccination against HPV 16 and 18 has the potential for effective prevention of high-grade precancer (cervical intraepithelial neoplasia [CIN)] 2/3) and ICC caused by these viruses (globally 50 and 70%, respectively) when employed in women prior to starting sexual activity. To provide data for decisions on HPV vaccination in China, we determined HPV type-distribution in ICC and CIN 2/3 from women of different regions within China. A multicenter study was conducted by randomized sampling of paraffin blocks of 664 ICC (630 squamous cell carcinoma [SCC]; 34 adenocarcinoma [ADC]), 569 CIN 2/3 cases from seven regions of China. Histological diagnosis was confirmed in 1,233 cases by consensus review. HPV DNA was detected using the SPF10 LiPA25 version 1 assay. HPV prevalence was 97.6% in SCC, 85.3% in adenocarcinoma, and 98.9% in CIN 2/3. HPV 16 (76.7%) and HPV 18 (7.8%) were the most common, together accounting for 84.5% of SCC, followed by HPV 31 (3.2%), HPV 52 (2.2%), and HPV 58 (2.2%). HPV positivity in SCC did not differ notably by region. However, SCC cases from women ≤34 years had higher HPV 16 positivity than women over 50 years, among whom HPV 52, 58, and 39 were more common. HPV 16 and 18 were under-represented, whereas HPV 31, 52, and 58 were over-represented in CIN2/3 compared to SCC. The potential impact of vaccines against oncogenic HPV types 16 and 18 is estimated to be high (84.5%) against total SCC. These data are critical for China’s future evaluation of the cost-effectiveness of current cervical cancer vaccines and of HPV-based screening guidelines.     

Lung adenocarcinoma and human papillomavirus infection

Over the past three decades, the incidence of lung adenocarcinoma has increased worldwide. Most individuals with lung adenocarcinoma (especially women) are nonsmokers. Reported risk factors for the development of lung adenocarcinoma include cigarette smoking; exposure to cooking fumes, air pollution, second-hand smoke, asbestos, and radon; nutritional status; genetic susceptibility; immunologic dysfunction; tuberculosis infection; and asthma. Human papillomavirus (HPV) infection is a known risk factor for the development of squamous cell carcinoma (SCC), but it has not been thoroughly assessed as a potential risk factor for the development of pulmonary adenocarcinoma. More than 50% of people are infected with HPV during their lifetimes, either via intrauterine or postnatal infection. Recent studies involving Taiwanese patients have demonstrated a possible association between HPV infection and the risk of developing pulmonary adenocarcinoma. HPV transmission pathways have not yet been conclusively identified. The observation of certain types of HPV in association with cervical and oral SCC raises the possibility of sexual transmission of HPV from the cervix to the oral cavity, with subsequent transmission to the larynx and then to the lung. HPV infection and metaplasia in lung tissue may increase an individual's susceptibility to the tumorigenesis of pulmonary adenocarcinoma. Further epidemiologic and pathologic investigations will be necessary to establish a causal relation.     

Clustering patterns of human papillomavirus infections among HIV-positive women in Kenya

Background

HIV-positive women are at increased risk of human papillomavirus (HPV) infection, and, especially, multiple infections compared to HIV-negative women. Whether certain HPV types have a tendency to cluster in multiple infections beyond or below what would be expected by shared risk factors (e.g., sexual behavior and the degree of immunosuppression) is unclear. We, therefore, investigated clustering patterns of 44 HPV types in HIV-positive women from Kenya.

Findings

HPV status was assessed on cervical scrapings from 498 women using GP5+/6+ PCR and reverse line blot. Logistic regression was used to model type-specific HPV positivity, adjusted for age, specific HPV type prevalence, CD4, combination antiretroviral therapy, and, in the Full Model, individual-level random effects that represent unobservable risk factors common to all HPV types. We found a modest excess of women with co-infections with 2 HPV types (1.12; 95% credible intervals: 1.03-1.21) in the Full Model but no significant associations of individual types. No significant deviations of observed/expected counts were observed for any 2-way combination of HPV types at either the chosen level of significance, p?=?0.00005, or at p?=?0.01. Findings were substantially similar when women with CIN2/3 were excluded and when they were stratified by use of anti-retroviral therapy or CD4 count.

Conclusions

HPV co-infections occurred at random in the cervix of HIV-positive women as previously found in HIV-negative women. The removal of HPV types through vaccination should not result, therefore, in an increase or decrease in the prevalence of HPV types not targeted by vaccination in immunosuppressed women.

     

Immunodeficiency and the risk of cervical intraepithelial neoplasia 2/3 and cervical cancer: A nested case‐control study in the Swiss HIV cohort study

HIV‐infected women are at increased risk of cervical intraepithelial neoplasia (CIN) and invasive cervical cancer (ICC), but it has been difficult to disentangle the influences of heavy exposure to HPV infection, inadequate screening and immunodeficiency. A case‐control study including 364 CIN2/3 and 20 ICC cases matched to 1,147 controls was nested in the Swiss HIV Cohort Study (1985–2013). CIN2/3 risk was significantly associated with low CD4+ cell counts, whether measured as nadir [odds ratio (OR) per 100‐cell/μL decrease = 1.15, 95% CI: 1.08, 1.22], or at CIN2/3 diagnosis (1.10, 95% CI: 1.04, 1.16). An association was evident even for nadir CD4+ 200–349 versus ≥350 cells/μL (OR = 1.57, 95% CI: 1.09, 2.25). After adjustment for nadir CD4+, a protective effect of >2‐year cART use was seen against CIN2/3 (OR versus never cART use = 0.64, 95% CI: 0.42, 0.98). Despite low study power, similar associations were seen for ICC, notably with nadir CD4+ (OR for 50 vs. >350 cells/μL= 11.10, 95% CI: 1.24, 100). HPV16‐L1 antibodies were significantly associated with CIN2/3, but HPV16‐E6 antibodies were nearly exclusively detected in ICC. In conclusion, worsening immunodeficiency, even at only moderately decreased CD4+ cell counts, is a significant risk factor for CIN2/3 and cervical cancer.     

Relationships of human papillomavirus type, qualitative viral load, and age with cytologic abnormality

Persistent cervical infections with carcinogenic human papillomaviruses (HPV) cause virtually all cervical cancer. Cytologic abnormalities are the manifestations of HPV infections used to identify women at risk. To compare the potential of the full range of anogenital HPV genotypes to induce cytopathic effects, we examined the influences of HPV type, viral load, and age on cytopathology among 1,222 women having a single HPV type at enrollment into a 10,000-woman population-based study in Costa Rica. Cervical specimens were tested for approximately 40 HPV types by MY09/MY11 L1 primer PCR and type-specific dot blot hybridization. Types were organized by phylogenetic species and cancer risk. PCR signal strength served as a qualitative surrogate for viral load. Overall, 24.8% [95% confidence interval (95% CI), 22.4-27.3] of single prevalent HPV infections had concurrent abnormalities (atypical squamous cells or worse) ranging from 0.0% to 80.0% based on HPV type. Noncarcinogenic alpha3/alpha15 types, although highly prevalent, uncommonly caused cytologic abnormalities (13.1%; 95% CI, 9.8-17.0). In contrast, one quarter to nearly one half of infections with a single major carcinogenic species type (alpha9/alpha11/alpha7/alpha5/alpha6) produced abnormalities. Greater abnormalities were observed with increasing qualitative viral load of carcinogenic types; fewer abnormalities were observed among older women (>54 years). A high percentage (46.2%) of detected abnormalities in women infected with HPV16 or related alpha9 types were high grade or worse, consistent with strong carcinogenicity, compared with 10.7% in women infected with alpha7 types, including HPV18, a major cause of adenocarcinoma. The lack of evident severe abnormalities associated with HPV18 and related HPV types might have implications for screening for poorly detected glandular and alpha7-related lesions.     

Type-specific Prevalence of Human Papillomavirus by Cervical Cytology among Women in Brasov,Romania

The oncogenic role of human papillomavirus (HPV) in triggering cervical cancer, the second most common cancer in women worldwide, is well established. Romania ranks in first place in Europe in terms of the incidence of cervical cancer. Geographical widespread data on HPV type-distribution are essential for estimating the impact of HPV vaccines and cervical cancer screening programmes. In this study we aimed to identify the prevalence of HPV genotypes and to establish correlations with abnormal cervical cytology among the female population of Brasov County, Romania. A total of 1,000 women aged 17.3-57 years, attending routine cervical examination in the Obstetrics and Gynecology Hospital of Brasov, Romania, and undergoing both cytological examination andHPV genotyping were screened. Infection with 35 different HPV genotypes was detected in 39.6% of cytological specimens. Overall HPV infections were highest in young women under 25 years (p<0.0001), in which cervical cytological abnormalities also reached the highest prevalence. Patients infected by HPV-16 or HPV-18 showed the highest prevalence of cervical cytological abnormalities. Some 48.2% of women with abnormal cytology were infected with high-risk HPV types whereas less than 3% of them were infected only with low-risk HPVtypes. Our study showed that the prevalence of high-risk HPV infection among Romanian women is higher compared to other studies in other geographic areas. Thus, we consider that in areas where there is an increased prevalence of high-risk HPV infections, HPV genotyping should be performed in all women aged between 18 and 45 years, and Pap test should be performed every 6 months in women with high-risk HPV infection, even those with previous normal cervical cytology.     

Invasive cervical cancers in the United States,Botswana and Kenya: HPV type distribution and health policy implications

Background

More deaths occur in African women from invasive cervical cancer (ICC) than from any other malignancy. ICC is caused by infection with oncogenic types of human papillomavirus (HPV). Co-infection with the human immunodeficiency virus (HIV) accelerates the natural history of ICC, and may influence the HPV type distribution. Because HPV vaccines are available, this malignancy is theoretically preventable, but the vaccines are largely type-specific in protection against infection. Data on specific HPV types causing ICC in African women is limited, and many studies utilized swab samples rather than actual cancer tissue. A previous study using archived, ICC tissue from women in Botswana identified an unusual HPV type distribution. A similar study was therefore performed in a second sub-Saharan country to provide additional information on the HPV type distribution in ICC.

Methods

Archived, formalin-fixed, paraffin-embedded ICCs were acquired from women in the United States, Kenya, or Botswana. DNA was extracted and HPV genotyping performed by Roche Linear Array. HIV sequences were identified in ICCs by PCR.

Results

HPV types 16 or 18 (HPV 16/18) were identified in 93.5 % of HPV-positive ICCs from the U.S., 93.8 % from Kenya, and 61.8 % from Botswana (p?<?0.0001). Non-HPV 16/18 types were detected in 10.9 % of HPV-positive cancers from the U.S., 17.2 % from Kenya, and 47.8 % from Botswana (p?<?0.0001). HIV was detected in 2.2, 31.5, and 32.4 % from ICCs from the U.S., Kenya, or Botswana, respectively (p?=?0.0002). The distribution of HPV types was not significantly different between HIVinfected or HIV-uninfected women. The percentages of ICCs theoretically covered by the bivalent/quadrivalent HPV vaccines were 93.5, 93.9, and 61.8 % from the U.S., Kenya and Botswana, respectively, and increased to 100, 98, and 77.8 % for the nanovalent vaccine.

Conclusions

HPV 16/18 caused most ICCs from the U.S. and western Kenya. Fewer ICCs contained HPV 16/18 in Botswana. HIV co-infection did not influence the HPV type distribution in ICCs from African women from the two countries. Available HPV vaccines should provide protection against most ICCs in the U.S. and Kenya. The recently developed nanovalent vaccine may be more suitable for countries where non-HPV 16/18 types are frequently detected in ICC.

     

Cervical human papillomavirus and HIV infection in women of child-bearing age in Abidjan, Côte d'Ivoire, 2010

Background:

We sought to document the association of Human immunodeficiency Virus (HIV) infection and immunodeficiency with oncogenic Human Papillomavirus (HPV) infection in women with no cervical neoplastic lesions identified through a cervical cancer screening programme in Côte d''Ivoire.

Methods:

A consecutive sample of women stratified on their HIV status and attending the national blood donor clinic or the closest HIV clinic was recruited during a cervical cancer screening programme based on the visual inspection. Diagnosis of HPV infection and genotype identification were based on the Linear Array; HPV test.

Results:

A total of 445 (254 HIV-positive and 191 HIV-negative) women were included. The prevalence of oncogenic HPV infection was 53.9% (95% confidence interval (CI) 47.9–59.9) in HIV-positive women and 33.7% (95% CI 27.1–40.3) in HIV-negative women (odds ratio (OR)=2.3 (95% CI 1.5–3.3)). In multivariate analysis, HIV-positive women with a CD4 count <200 cells mm³ or between 200 and 499 cells mm³ were more likely to harbour an oncogenic HPV compared with women with a CD4 count ⩾500 cells mm³ with OR of 2.8 (95% CI 1.1–8.1) and 1.7 (95% CI 1.0–2.9), respectively.

Conclusion:

A high prevalence of oncogenic HPV was found in women with no cervical neoplastic lesions, especially in HIV-positive women. Despite antiretroviral use, immunodeficiency was a main determinant of the presence of oncogenic HPV.