Detection of High-risk Human Papillomavirus Types 16 and 18 but not 33 and 52 in External Genital Warts from Iranian Females

Background: External genital warts (EGW) are relatively common sexually transmitted diseases. In themajority of cases, low-risk human papilomaviruses (HPV), such as HPV-6 and HPV-11, are responsible but,high-risk types may also be detected and this has a bearing on vaccines for cervical cancer prevention. In thisstudy the incidence of the high-risk HPV types 16, 18, 33 and 52 in EGWs of females from the southwest of Iranwas assessed. Methods: Seventy-nine women with EGWs participated in this study. Quantitative real-time PCRwith gene specific primers and probes for the E6 gene of HPV-16, 18, 33 and 52, were used for the detection ofHPV DNA in the tissue and blood samples. Results: Of the 79 tissue specimens, 13 (16.5%) were HPV positive,only genetic materials of HPV-16 and HPV-18 being detected, twelve patients (15.2%) were positive only forHPV-18 and the coexistence of HPV-16 and HPV-18 was shown in one patient. Only one plasma sample showedevidence of HPV-16 with very low viral load. Conclusion: Our data showed that high-risk HPV types can befound in the tissue specimens of EGW samples obtained from female patients in the Southwest of Iran, withHPV-18 as the most abundant type; however, additional studies with a larger population are required to provethe finding and help to determine the most appropriate type of virus for vaccine design for Iranian women.     

Human papillomavirus genotypes in women with invasive cervical cancer with and without human immunodeficiency virus infection in Botswana

Cervical cancer remains a significant cause of morbidity and mortality in women worldwide and is the leading cause of cancer-related death in Botswana. It is well established that women with HIV have a higher risk of persistent HPV infection leading to cervical cancer. We assessed HPV prevalence and genotype distribution in 126 tissue specimens from confirmed invasive cervical cancer cases using Abbott real-time PCR assay. Overall, 88 (69.8%) women were HIV-infected. Fifty-seven (64.8%) of the HIV-infected women had a baseline CD4⁺ count ≥350 cells/μl, and 82 (93.2%) were on antiretroviral therapy at the time of cervical cancer diagnosis. The median age of HIV-infected patients was significantly younger than that of HIV-uninfected patients (p < 0.001). HPV DNA was detected in all of 126 (100%) of tissues analyzed in our study. The HPV genotypes identified included the HPV-16 (75.4%), HPV-18 (28.6%) and other high-risk (hr) HPV genotypes (16.7%). HIV infection was positively associated with the presence of the HPV-16 genotype (p = 0.036), but not with HPV-18 or with other high-risk (hr)-HPV genotypes. Thirty-three percent of the patients had multiple hr-HPV genotypes, with higher rates in HIV-infected women. These results highlight the importance and potential impact of large-scale HPV vaccination programs covering HPV-16 and HPV-18 genotypes in countries like Botswana with high burden of HIV infection.     

新疆地区宫颈癌和CIN患者HPV-16感染和血清中HPV-16 L1抗体的检测及其临床意义

目的 探讨宫颈癌和宫颈上皮内瘤变（CIN）患者血清中HPV 16 L1抗体水平及其与HPV-16感染的关系。方法 收集宫颈癌患者51例和CIN（包括CINⅠ、CINⅡ、CINⅢ）患者44例。取患者宫颈病变组织并提取组织DNA,PCR检测HPV-16 DNA。同时取患者血样,酶联免疫吸附试验（ELISA）检测血清样品中HPV-16 L1抗体。结果 宫颈癌组中HPV-16 DNA的阳性率为82.4％,CIN组为52.3％。宫颈癌组血清HPV-16 L1抗体阳性率为70.6％,CIN组为79.5％。宫颈癌组中HPV-16 DNA阳性而HPV-16 L1抗体阴性的比例为27.5％,显著高于CIN组的9.1％（P＜0.05）;宫颈癌组HPV-16 DNA阴性而HPV-16L1抗体阳性的比例为15.7％,显著低于CIN组的36.4％（P＜0.05）。宫颈癌组HPV-16 DNA和患者HPV-16 L1抗体均阳性的重合率为54.9％,CIN组为43.2％。结论 CIN和宫颈癌患者HPV-16 L1抗体的产生与HPV-16 DNA的检出率相关,血清中HPV-16 L1抗体可作为宫颈癌和CIN病程的辅助诊断指标。     

Distribution of HPV-16 Intratypic Variants among Women with Cervical Intraepithelial Neoplasia and Invasive Cervical Cancer in Mongolia

Objectives. Infection with high-risk human papillomavirus (HPV) is a critical factor associated withcarcinogenesis of the uterine cervix. HPV-16 is most frequently found, and is further subclassified into intratypicvariants based on the nucleotide sequences of the viral genes. Although certain HPV-16 variants are reported tobe associated with the progression of cervical lesions, these relationships remain controversial with differentresults for different populations. To provide data for another population, we investigated the prevalence ofHPV-16 and distributions of its intratypic variants among Mongolian women with cervical intraepithelialneoplasia (CIN) and invasive cervical cancer. Materials and Methods. We analyzed samples from 374 randomlyselected women who attended the National Cancer Center of Mongolia between January 2002 and July 2007,including 147 invasive cervical cancer patients, 127 CIN patients and 100 age-matched controls who werecytologically normal. HPV genotyping was initially conducted, followed by variant analysis for HPV-16-positivesamples by nucleotide sequencing of the E6 gene. The HPV data were evaluated statistically for correlationswith the patients’ clinical data. Results. HPV genotyping detected 101 HPV-16-positive samples. Among thesesamples, 92 were available for subsequent variant analysis, including 66 invasive cervical cancer samples, 25CIN samples and 1 cytologically normal sample. A total of 14 different variants were identified. All 14 variantsbelonged to the European lineage, and the European prototype was detected in 66% (61/92) of the samples.Among the remaining 31 variants, variants with the T350G nucleotide change were predominant (13/31, 42%),followed by variants containing G94A (11/31, 35%), G176A (4/31, 13%) and G274T (2/31, 7%) . There were nosignificant differences among all the variants regarding their distributions in CIN and invasive cervical cancers.Conclusions. HPV-16 variants of the European lineage were exclusively distributed among the Mongolian womenexamined, and the European prototype was overwhelmingly predominant. Since no significant differences werefound between the types of variants and severities of the cervical lesions, it is possible that racial or geographicfactors may have some influences on these relationships.     

Immunoglobulin-A and -G responses against virus-like particles (VLP) of human papillomavirus type 16 in women with cervical cancer and cervical intra-epithelial lesions

Immunoglobulin-A and -G (IgA and IgG) responses against HPV-16-like particles (VLP) were tested by ELISA in 104 women with cervical abnormalities, 26 atypical cells of undetermined significance (ASCUS) and 14 cytologically normal women with HPV DNA. As controls, 130 age-matched cytologically normal women with no HPV DNA were selected from the population in which the cases were generated. The existence of HPV DNA in cervical samples was tested by a PCR-based method. The normal women positive with HPV16 DNA were followed up at 4- to 7-month intervals for 16 to 24 months. IgA and IgG antibodies against HPV-16 VLP were frequently detected in these women repeatedly positive with HPV-16 DNA, suggesting that persistent HPV infection is crucial for effective antibody responses against the viruses. IgA response appears earlier and persists longer than IgG response. Women with HPV DNA of types 16, 31/33/35, 58 and unknown types showed significantly higher seropositivity for both IgA and IgG antibodies than the controls (p < 0.05 for both). No significant seropositivity for IgA or IgG was detected in the HPV-18/45-DNA-positive group. HPV 31/33/35, 58 appear to be types close to HPV 16, whereas HPV 18/45 appears to be distinct from HPV 16 in antigenicity. IgA and IgG responses against HPV-16 VLP were more frequently observed in women with normal cervices with HPV DNA, ASCUS, HSIL and cervical cancer than in the controls. Strong IgA and IgG responses depended on HPV-16 infection in HSIL and cervical cancer, but there was no correlation between the serological responses and the status of HPV DNA in ASCUS and LSIL. Antibody positivity reflects persistent viral infection that may increase the risk for malignant progression of the cervix. This serological assay using HPV 16-VLP may therefore be useful as a new diagnostic tool supplementing cervical cytological tests. Int. J. Cancer 75:529–535, 1998.© 1998 Wiley-Liss, Inc.     

Detection and quantitation of human papillomavirus DNA in the plasma of patients with cervical carcinoma.

Human papillomaviruses (HPVs) play a central role in the development of cervical carcinoma. Plasma DNA from 232 patients taken at diagnosis or after treatment for invasive cervical cancer (n = 175) or carcinoma in situ (n = 57) and 60 normal controls were examined for HPV-16 or HPV-18 E7 DNA by conventional and real-time quantitative PCR assays. We found HPV-16 or HPV-18 E7 DNA in 6.9% (11 of 175) of invasive cervical cancer cases (18.1% of cases positive for HPV-16 or HPV-18 at the genital tract), 1.8% (1 of 57) of carcinoma in situ, and 1.7% (1 of 60) of normal controls by conventional PCR. Quantitative PCR identified the highest concentrations of HPV DNA (copy number of HPV/ml of plasma) in patients with invasive cervical cancer (mean, 11,163; median, 183.5), followed by a level of 8 in the single carcinoma in situ case and 0 copies in the normal control initially positive by conventional PCR. HPV DNA can be detected in the plasma of some patients with HPV-positive cervical tumors. It remains to be demonstrated whether quantitative PCR analysis of HPV DNA in plasma may have utility in patients at high risk of recurrent disease.     

Case-control study of human papillomaviruses and cervical cancer in Latin America

Human papillomavirus (HPV) types 16 and 18 have been implicated as risk factors for cervical dysplasia and neoplasia. However, most studies have been observational, uncontrolled and conducted in populations at low risk for invasive cancer. We report a pilot case-control study of incident invasive cervical cancer in Panama, Costa Rica and Bogota, Colombia. Between July and September 1985 we enrolled 46 consecutive newly diagnosed invasive cervical cancer cases and 51 age-matched control women. Subjects were interviewed and samples collected for HPV DNA assays. HPV infection was defined by a filter in situ DNA hybridization technique under non-stringent and stringent conditions against HPV-6/11, 16 and 18 DNA probes. More cases (91%) than controls (63%) had HPV DNA detected (non-stringent) and more cases than controls had HPV-16 or 18 DNA (67% vs. 43%, p = 0.02). Age at first intercourse was the most significant risk factor for HPV 16/18 infection in all subjects. Smoking was significantly associated with cervical cancer (52% of cases vs. 27% controls) but was not associated with HPV infection.     

Human papillomavirus detected in female breast carcinomas in Japan

To investigate the aetiological role of human papillomavirus (HPV) in breast cancer, we examined the presence, genotype, viral load, and physical status of HPV in 124 Japanese female patients with breast carcinoma. Human papillomavirus presence was examined by PCR using SPF10 primers, and primer sets targeting the E6 region of HPV-16, -18, and -33. The INNO-LiPA HPV genotyping kit was used to determine genotype. Human papillomavirus DNA was detected in 26 (21%) breast carcinomas. The most frequently detected HPV genotype was HPV-16 (92%), followed by HPV-6 (46%), HPV-18 (12%), and HPV-33 (4%). In 11 normal epithelium specimens adjacent to 11 HPV-16-positive carcinomas, 7 were HPV-16-positive. However, none of the normal breast tissue specimens adjacent to HPV-negative breast carcinomas were HPV-positive. The real-time PCR analysis suggested the presence of integrated form of viral DNA in all HPV-16-positive samples, and estimated viral load was low with a geometric mean of 5.4 copies per 10(4) cells. In conclusion, although HPV DNA was detected in 26 (21%) breast carcinomas and, in all HPV-16-positive cases, the HPV genome was considered integrated into the host genome, their low viral loads suggest it is unlikely that integrated HPV is aetiologically involved in the development of Japanese breast carcinomas that we examined.     

新疆维吾尔族妇女宫颈癌HPV感染型别分布研究

目的探讨人乳头瘤状病毒(HPV)在新疆南部维吾尔族妇女宫颈癌患者的型别分布情况,为开发适宜该地区的HPV疫苗提供一定的理论依据.方法收集2008年6月至2010年4月就诊于新疆维吾尔自治区人民医院妇科的经病理确诊的新疆南部地区维吾尔族妇女宫颈癌患者120例,利用聚合酶链反应(PCR)和基因芯片技术检测HPV DNA并分...     

Human papillomavirus 16 and 18 L1 serology compared across anogenital cancer sites

Human papillomavirus (HPV) DNA has been detected in the great majority of cancers of the uterine cervix and anus, whereas the association of HPV DNA with cancer at other anogenital sites has produced less consistent results. This study was designed to compare HPV exposure among anogenital cancer cases and matched controls. Cases (1782) of anogenital cancer diagnosed in the Seattle area from 1978 to 1998 were identified and interviewed. Their responses were compared with those of 2383 age- and sex-matched controls. Blood was drawn at interview from both cases and controls and tested for antibodies to HPV-16 and HPV-18. Tissue blocks were tested for HPV DNA for 649 cases. Serum antibodies to HPV-16 were associated with in situ and invasive cancer at all sites among men and women with the exception of in situ penile cancer. Anti-HPV-18 antibodies were associated with cancers at all sites among women. The increased risk of cancer associated with HPV-16 seropositivity ranged from odds ratio = 1.8 (95% confidence interval, 1.4-2.5) for adenocarcinoma of the cervix to odds ratio = 5.9 (95% confidence interval, 3.4-10.3) for anal cancer in men. Associations between seroprevalence and cancers were stronger when analyses were restricted to HPV-16- or HPV-18 DNA-positive cases. HPV DNA was detected in >80% of cancers from all sites tested. HPV-16 DNA was the type most frequently detected at all sites (range, 40.9-82.2%). HPV-18 DNA was detected in 44.7% of adenocarcinomas of the cervix but detected much less often (2.6-18.1%) at other sites. These findings support an important role for HPV infection in anogenital cancer at all sites. Differences in the proportion of seropositives among HPV-16 DNA-positive cases by site suggest either that the immune response varies by site or that cancer development may lead to changes in antibody responses in a site-specific fashion.     

Cervical carcinoma in Southern Mexico: Human papillomavirus and cofactors

Background: This study was conducted to determine human papillomavirus (HPV) types in women with cervical cancer (CC) and normal cervical cytology in the Southern region of Mexico, and to know the contribution of HPV types and cofactors in cervical cancer etiology. Methods: A case-control study was performed in 133 women with CC and 256 controls. HPV detection was done by MY09/11 and GP5+/GP6+ PCR systems and typing by restriction fragment length polymorphism or DNA sequencing. Results: HPV was found in 100% of CC and 35.5% of controls. The genotype distribution in CC was: HPV 16 (66.8%), 18 (9%), 31 (7.5%), 45 (4.5%), 58 (3.7%), 69 (3%), 52 (1.6%), 6, 11, 33, 56, and 67 (0.8% each). Among controls, HPV 33 followed by HPV 16 were the most frequent. Cervical cancer was associated with HPV 16 (OR = 573.5), HPV 18 (OR = 804.4), and undetermined risk HPV (types 67 and 69) (OR = 434.3). Age at first intercourse <16 years (OR = 9.6) and ≥3 births (OR = 16) were significant risk factors for CC. Conclusions: HPV 16, by far, is the most frequent type in CC, HPV 16 and 18 are responsible for 75.8% of the CC cases and high-risk HPV for 94.7%, which is useful data to take into account in vaccination programs. HPV 33 is the most frequent type in controls and high-risk HPV are more common than low-risk HPV.     

宫颈高级别病变与HPV感染型别分析

目的探讨HPV在宫颈高级别病变中的感染率及感染型别。方法采用导流杂交法分别检测CINII～Ⅲ30例和宫颈癌患者160例HPV基因型别,比较HPV感染与宫颈病变的关系。结果CINⅡ～III和宫颈癌患者HPV感染率均为90％,且以单型别感染为主,分别为70．37％（19／27）、81．94％（118／144）;在CIN II～Ⅲ中HPV58型、52型感染居多,宫颈癌则以HPV16型、18型感染最常见;无论宫颈鳞癌还是宫颈腺癌,以HPV16型检出率最高。结论HPV16型、18型是宫颈癌的主要致病型,不同病理类型并无HPV型别上的差异;宫颈上皮高级别内瘤变则以HPV58型、52型感染为主;对HPV58型、52型感染者应重视随访。     

Occurrence of antibodies to L1, L2, E4 and E7 gene products of human papillomavirus types 6b, 16 and 18 among cervical cancer patients and controls.

Sera from 118 women of 33 to over 90 years of age, with or without a history of cervical squamous-cell carcinoma, were examined for the presence of antibodies to HPV-6b, HPV-16 and HPV-18, L1, L2, E4, and E7 gene products by the use of bacterially derived beta-Gal fusion proteins and Western-blot analysis. Among the cervical cancer patients, 29/46 (63.0%) were positive for antibodies to E4 and/or E7 of HPV-16 and/or E7 of HPV-18. In contrast, only 2 of 31 (6.5%) non-genital cancer patients and 4 of 41 (9.8%) healthy individuals were antibody-positive for HPV-16 E4 or E7, while antibodies to the homologous proteins of HPV-18 could not be detected. Prevalence rates of antibodies to the HPV-16/18 late proteins were 25/46 (54.3%) in the cervical carcinoma group, 13/31 (41.9%) among women with non-genital cancer types, and 18/41 (43.9%) among normal, healthy individuals. Antibodies to HPV-6b late gene products ranged between 6.5% and 12.2% in the different patient groups. Antibodies to HPV-6b E4 and E7 were detected only once. By studying an additional control group of 207 women with a different age distribution, age-dependence of antibodies to HPV gene products could be ruled out. Whereas antibodies to late proteins may indicate that, regardless of clinical stage, HPV infections are wide-spread among the female population, the striking difference between the prevalence rates of antibodies to early proteins of HPV-16 and HPV-18 among cervical cancer patients and controls (p less than 0.001) supports the idea of the involvement of these virus types in carcinogenesis of the cervix.     

ТР53 Codon 72 Polymorphism and Human Papilloma Virus-Associated Cervical Cancer in Kyrgyz Women

Background: The aim of this study was to ascertain the magnitude of association of gene ТР53 Arg72Pro polymorphicmarker with cervical cancer (CC) in Kyrgyz women. Methods: We identified and included 205 women of Kyrgyzethnicity for this case-control study, of whom N=103 were women (mean age 53.5 ± 10.0 years) with histologicallyconfirmed CC and N=102 controls (mean age 46.5 ± 8.5 years). We detected human papilloma virus (HPV) DNA types16 and 18 using polymerase chain reaction (PCR) with hybridization/fluorescent detection. Genotypes of ТР53 geneArg72Pro polymorphism were identified using PCR-RFLP assay. Results: Eighty-eight percent (90/103) women withCC had HPV, of whom 43.4% (39/90) had HPV type 16, 24.4% (22/90) had HPV type 18, whereas 32.2% (29/90)carried both types. The univariate analysis of allele and genotype distribution of Arg72Pro polymorphic marker of ТР53gene showed no difference between CC and control groups (χ2=1.24, р=0.54). However, when CC cases associated withHPV were tested against controls, Arg72 allele and Arg72Arg genotype prevalence were greater compared to controls(χ²=7.25; р=0.027 for genotypes and χ²=6.83; р=0.009 for alleles). In HPV-positive women, Arg72Arg genotype ofТР53 gene was associated with a 1.85-fold increase in the likelihood of CC (OR=1.85 [95% confidence interval (CI)1.03-3.32]), whereas Arg72 allele increased this likelihood 1.94-fold (OR=1.94 [95% CI 1.20-3.15]). Conclusions:Arg72Arg genotype and Arg72 allele of ТР53 gene in Kyrgyz women increase the risk of HPV-associated CC.     

The Prevalence of Human Papillomavirus in Cervical Cancer in Iran

Background: The human papiloma virus (HPV), which is sexually transmitted, and most commonly causesgenital warts, has been linked to cervical intraepithelial neoplasia and invasive carcinoma. Of ninety plus types ofHPV, HPV-16 is the most prevalent in cervical cancer, followed by HPV-18, and HPV-33. As HPV’s implication hasnot been assessed in the Middle East the main focus of this retrospective study was to determine the prevalence ofHPV –16,18, and 33 in cases of cervical cancer from Iran.Material and Methods: This retrospective study covered 100 patients with uterine cervical carcinomas who werereferred to two referral centers for cancer in Tehran-Iran. Pathological blocks were collected for these cases andinitial review of the blocks showed poor specimens in 18 cases, which left 82 cases for the study. These samples werehistologically examined to verify the presence and the type of carcinoma. The next step was in situ hybridzation forthe detection of HPV common DNA. In Situ hybridization was preformed on all samples. Finally, Polymerase ChainReaction (PCR) was preformed for the HPV types 16, 18, and 33. PCR amplification of exon 5 of the p53 gene wasused as an internal control for the integrity of DNA. Takara PCR Human papilloma Detection method was usedwhich includes primer for HPV 16, 18, and 33. Three primers were used alone, or in combination, in order toincrease the sensitivity of the detection.Results: The majority of tumors were squamous cell carcinomas (87%). The rest were adenosquamous carcinomaand adenocarcinomas. None of the 82 different cervical carcinoma tissue samples were found to be positive by in situhybridization. In the PCR samples, amplification of DNA was observed for 69 tumor specimens. In the remainning13cases, the DNA in fixed tissue was degraded, as verified by the absence of an internal control band (p53). Out of thetotal 69 tumors (85.5%) with adequate DNA contained HPV band on PCR. The majority (73.9%) of HPV positivetumors contained HPV-16; the rest (11.6%) demonstrated type 18 and 33. There was no correlation between thehistology of carcinoma and presence of types of HPV.Conclusion: The prevalence of HPV in carcinomas of uterine cervix in Iran is similar to those reported in otherregions of the world. Similarly, it appears that HPV-16 is the most common type associated with cervical cancer inIran. Further studies on larger samples of patients, particularly in those with pre-invasive forms of the disease, areneeded to elucidate the carcinogenic role of HPV types in cervical cancer in Iranian women.     

Human papillomavirus genotype distribution and cervical squamous intraepithelial lesions among high-risk women with and without HIV-1 infection in Burkina Faso

Human papillomavirus (HPV) infection and cervical squamous intraepithelial lesions (SILs) were studied in 379 high-risk women. Human papillomavirus DNA was detected in 238 of 360 (66.1%) of the beta-globin-positive cervical samples, and 467 HPV isolates belonging to 35 types were identified. Multiple (2-7 types) HPV infections were observed in 52.9% of HPV-infected women. The most prevalent HPV types were HPV-52 (14.7%), HPV-35 (9.4%), HPV-58 (9.4%), HPV-51 (8.6%), HPV-16 (7.8%), HPV-31 (7.5%), HPV-53 (6.7%), and HPV-18 (6.4%). Human immunodeficiency virus type 1 (HIV-1) seroprevalence was 36.0%. Human papillomavirus prevalence was significantly higher in HIV-1-infected women (87 vs 54%, prevalence ratio (PR) = 1.61, 95% confidence interval (CI): 1.4-1.8). High-risk HPV types (71 vs 40%, PR = 1.79, 95% CI: 1.5-2.2), in particular HPV-16+18 (22 vs 9%, PR = 2.35, 95% CI: 1.4-4.0), and multiple HPV infections (56 vs 23%, PR = 2.45, 95% CI: 1.8-3.3) were more prevalent in HIV-1-infected women. High-grade SIL (HSIL) was identified in 3.8% of the women. Human immunodeficiency virus type 1 infection was strongly associated with presence of HSIL (adjusted odds ratio = 17.0; 95% CI 2.2-134.1, P = 0.007) after controlling for high-risk HPV infection and other risk factors for HSIL. Nine of 14 (63%) HSIL cases were associated with HPV-16 or HPV-18 infection, and might have been prevented by an effective HPV-16/18 vaccine.     

A comprehensive natural history model of HPV infection and cervical cancer to estimate the clinical impact of a prophylactic HPV-16/18 vaccine

The object of our study is to project the impact of a prophylactic vaccine against persistent human papillomavirus (HPV)-16/18 infection on age-specific incidence of invasive cervical cancer. We developed a computer-based mathematical model of the natural history of cervical carcinogenesis to incorporate the underlying type-specific HPV distribution within precancerous lesions and invasive cancer. After defining plausible ranges for each parameter based on a comprehensive literature review, the model was calibrated to the best available population-based data. We projected the age-specific reduction in cervical cancer that would occur with a vaccine that reduced the probability of acquiring persistent infection with HPV 16/18, and explored the impact of alternative assumptions about vaccine efficacy and coverage, waning immunity and competing risks associated with non-16/18 HPV types in vaccinated women. The model predicted a peak age-specific cancer incidence of 90 per 100,000 in the 6th decade, a lifetime cancer risk of 3.7% and a reproducible representation of type-specific HPV within low and high-grade cervical precancerous lesions and cervical cancer. A vaccine that prevented 98% of persistent HPV 16/18 was associated with an approximate equivalent reduction in 16/18-associated cancer and a 51% reduction in total cervical cancer; the effect on total cancer was attenuated due to the competing risks associated with other oncogenic non-16/18 types. A vaccine that prevented 75% of persistent HPV 16/18 was associated with a 70% to 83% reduction in HPV-16/18 cancer cases. Similar effects were observed with high-grade squamous intraepithelial lesions (HSIL) although the impact of vaccination on the overall prevalence of HPV and low-grade squamous intraepithelial lesions (LSIL) was minimal. In conclusion, a prophylactic vaccine that prevents persistent HPV-16/18 infection can be expected to significantly reduce HPV-16/18-associated LSIL, HSIL and cervical cancer. The impact on overall prevalence of HPV or LSIL, however, may be minimal. Based on the relative importance of different parameters in the model, several priorities for future research were identified. These include a better understanding of the heterogeneity of vaccine response, the effect of type-specific vaccination on other HPV types and the degree to which vaccination effect persists over time.     

Prevalence of Human Papillomavirus Genotypes in Women from Cozumel,Mexico

Background: Human papillomavirus (HPV) subtypes 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 68 have beenimplicated in the development of cervical cancer (CC). These 13 high risk HPV types have been shown to be presentin up to 99.7% of CC samples. In Mexico, this cancer is the leading cause of death from malignancy among women.The aim of this study was to determine the prevalence of different HPV genotypes and investigate epidemiological aspectsassociated with HPV infection in women from Cozumel. Material and methods: We performed an epidemiological,prospective and cross sectional study with 1,187 who accepted participation in a campaign of screening for CC, duringthe period 2014 to 2015. Data on epidemiological and socio-economic variables were obtained. Cervical cells werecollected for detection of HPV DNA and typing of HPV-positive samples by Multiplex PCR, using a commercialkit for 16 viral genotypes. Results: The overall prevalence of HPV in women from Cozumel was 15.8 % (188/1,187),either single (13.6%) or multiple (2.19 %). The most common HPV types , in descending order of frequency, were 58(24.5 %), 59 (13.3 %), 39 (12.2 %) and 66 (9.6 %). The most frequent high risk types were HPV-58 and -59 and of lowrisk HPV types the most common was HPV-6. Number of sexual partners (OR=4.78; 95% CI= 2.73-8.37; P=<0.0001)and age of first coitus (OR=0.51; 95% CI=0.32-0.81; P=<0.0011) were significantly associated with HPV infection.Conclusions: Our data indicate that the overall incidence of high risk HPV infection in Cozumel is low as compared toother studies worldwide, with a different profile of subtypes. However, as expected, risky sexual behavior was foundassociated with positive cases of HPV. These results highlight the need for establish strategies to prevent HPV acquisitionand evaluate the impact of a vaccine application in the Cozumel population.     

Correlation of cervical carcinoma and precancerous lesions with human papillomavirus (HPV) genotypes detected with the HPV DNA chip microarray method

BACKGROUND: Human papillomavirus (HPV) infection is considered to play an important role in the development of cervical carcinoma, and it is known that certain HPV types, such as HPV-16 and HPV-18, are highly associated with cervical carcinoma. However, the pathologic behavior of other HPV types remains unclear. Recently, a new HPV detection technique, the HPV DNA chip, was introduced. The HPV DNA chip harbors 22 HPV probes and has the advantage of being able to detect 22 HPV types simultaneously. To evaluate the quality of the HPV DNA chip method and to identify HPV types related to cervical carcinoma and precancerous lesions, the authors performed HPV typing in cervical specimens from 1983 patients and compared their cytologic and histologic diagnoses. METHODS: The HPV DNA chip was used for HPV typing. Among 1983 patients who were tested for HPV types, cervical smear cytology was performed in 1650 patients, and 677 of those patients underwent cervical biopsy. RESULTS: Among the 1650 smears that were examined cytologically, 92.7% (114 of 123 smears) of low-grade squamous intraepithelial lesions (LSILs), 98.1% (106 of 108 smears) of high-grade squamous intraepithelial lesions (HSILs), and 96.3% (51 of 53 smears) of carcinomas were HPV positive, compared with only 35.1% of smears with normal cytology that were HPV positive. HPV-16 was the most prevalent type (chi-square test; P < 0.01) in LSILs (28.5%), in HSILs (51.9%), and in carcinomas (62.5%) followed by HPV-58 and a group of low-risk types (HPV-6, HPV-11, HPV-34, HPV-40, HPV-42, HPV-43,and HPV-44) in LSILs. HPV-58 (15.7%), HPV-18 (6.7%), and HPV-52 (4.6%) were the next most prevalent types after HPV-16 in HSILs. HPV-18 (11.4%) and HPV-58 (11.4%) were the second most common types in carcinomas. HPV-58 had the highest positive predictive value (54.9%) for the detection of histologically confirmed HSIL or carcinoma, whereas HPV 16 had the highest negative predictive value (80.6%). The sensitivity (96.0%) of the HPV test using the DNA chip method for detecting HSIL or carcinoma was superior compared with the sensitivity of cytologic diagnosis (83.6%). CONCLUSIONS: The HPV DNA chip provides a very sensitive method for detecting 22 HPV genotypes with reasonable sensitivity (96.0%) and reasonable negative predictive value (96.9%), and it overcomes the low sensitivity of cytologic screening for the detection of HSIL or carcinoma. HPV-58, HPV-52, and HPV-56, as well as HPV-16 and HPV-18, were associated highly with HSIL and carcinoma in the current large series. In addition, multiple HPV infection was associated less frequently with cervical carcinoma and with precancerous lesions compared with normal cytology.     

Favorable clinical outcome of cervical cancers infected with human papilloma virus type 58 and related types

To determine whether the status of human-papillomavirus (HPV) infection affects the clinical outcome of cervical carcinoma (CC), HPV genotype was prospectively determined in 94 consecutive CC cases subsequently followed for a median duration of 37.5 months. With a consensus PCR-RFLP method of HPV genotyping, 81 (86.2%) cancers were positive for HPV DNA. They were classified, according to the phylogenic similarities, into HPV-16-related (type 16, n = 45; type 31, n = 2), HPV-58-related (type 58, n = 17; type 33, n = 3; type 52, n = 2) and HPV-18-related (type 18, n = 8; type 68, n = 1) groups, and analyzed in relation to clinical outcome. The following results were observed: (i) Type-58-related HPVs were more prevalent in the old age (older than the median age of 52) group than in the young age group (41% vs. 14.6%, p = 0.045); (ii) 63% (5/8) of patients with advanced stages (III and IV) were HPV-negative, a figure much higher than that (9.3%, 8/84) of patients with early stages (stage I and II) (p = 0.002); (iii) the occurrence of adenocarcinoma or adenosquamous carcinoma was higher in the HPV-18-related group (50%) than in the HPV-16-related (33.3%) or the HPV-58-related (16.7%) groups (p = 0.024); (iv) the status of lymph-node metastasis and tumor grade did not correlate with HPV status; (v) 5-year survival rates were 90.2%, 80% and 74% for HPV-58-, HPV-16- and HPV-18-related groups, respectively (p = 0.03, after adjustment for tumor stage); (vi) in comparison with the HPV-16-related group, the relative risk of death in the HPV-58- and the HPV-18-related groups were 0.32 [95% CI, 0.07-1.49] and 1.87 [0.36-14.9] respectively. HPV genotype appears to affect the clinical behavior and outcome of cervical cancer. HPV-58-related types are prevalent in the older population, and appear to confer a favorable prognosis. Int. J. Cancer (Pred. Oncol.) 84:553-557, 1999.