scholarly journals Post HocAnalysis of the PATRICIA Randomized Trial of the Efficacy of Human Papillomavirus Type 16 (HPV-16)/HPV-18 AS04-Adjuvanted Vaccine against Incident and Persistent Infection with Nonvaccine Oncogenic HPV Types Using an Alternative Multiplex Type-Specific PCR Assay for HPV DNA

2014 ◽  
Vol 22 (2) ◽  
pp. 235-244 ◽  
Author(s):  
Frank Struyf ◽  
Brigitte Colau ◽  
Cosette M. Wheeler ◽  
Paulo Naud ◽  
Suzanne Garland ◽  
...  

ABSTRACTThe efficacy of the human papillomavirus type 16 (HPV-16)/HPV-18 AS04-adjuvanted vaccine against cervical infections with HPV in thePapillomaTrial againstCancerin YoungAdults (PATRICIA) was evaluated using a combination of the broad-spectrum L1-based SPF10PCR-DNA enzyme immunoassay (DEIA)/line probe assay (LiPA25) system with type-specific PCRs for HPV-16 and -18. Broad-spectrum PCR assays may underestimate the presence of HPV genotypes present at relatively low concentrations in multiple infections, due to competition between genotypes. Therefore, samples were retrospectively reanalyzed using a testing algorithm incorporating the SPF10PCR-DEIA/LiPA25plus a novel E6-based multiplex type-specific PCR and reverse hybridization assay (MPTS12 RHA), which permits detection of a panel of nine oncogenic HPV genotypes (types 16, 18, 31, 33, 35, 45, 52, 58, and 59). For the vaccine against HPV types 16 and 18, there was no major impact on estimates of vaccine efficacy (VE) for incident or 6-month or 12-month persistent infections when the MPTS12 RHA was included in the testing algorithm versus estimates with the protocol-specified algorithm. However, the alternative testing algorithm showed greater sensitivity than the protocol-specified algorithm for detection of some nonvaccine oncogenic HPV types. More cases were gained in the control group than in the vaccine group, leading to higher point estimates of VE for 6-month and 12-month persistent infections for the nonvaccine oncogenic types included in the MPTS12 RHA assay (types 31, 33, 35, 45, 52, 58, and 59). Thispost hocanalysis indicates that the per-protocol testing algorithm used in PATRICIA underestimated the VE against some nonvaccine oncogenic HPV types and that the choice of the HPV DNA testing methodology is important for the evaluation of VE in clinical trials. (This study has been registered at ClinicalTrials.gov under registration no. NCT00122681.)

2016 ◽  
Vol 2 (3_suppl) ◽  
pp. 1s-1s
Author(s):  
Mu Mu Shwe ◽  
Hlaing Myat Thu ◽  
Khin Shwe Mar

Abstract 12 A causal role for human papillomavirus (HPV) associated cancers of vulva, penile, and anus is supported by evidence from molecular and epidemiologic investigations. This study detected the oncogenic HPV genotypes in vulva cancers, penile cancers and anal cancers by a cross-sectional descriptive study in 2013. A total of 100 paraffin embedded biopsy tissues of histologically confirmed vulva cancers, penile cancers and anal cancers within past five years during 2008 and 2012 were studied. Those cases were 61 vulva cancers from Central Women Hospital, Yangon and 30 penile cancers and 9 anal cancers from Yangon General Hospital. HPV-DNA testing and genotyping were performed by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). Consensus sequence primer pairs within the E6 andE7 open reading were used to amplify oncogenic HPV genotypes (HPV-16,-18,-31,-33,-35,-52b,-58). Restriction enzymes were used for determination of specific HPV genotypes. HPV was identified in 36.1% of vulva cancers (22/61), 26.7% of penile cancers (8/30) and 44.4% of anal cancers (4/9). In vulva cancers, HPV-33 was the most common genotype (40.9%) followed by HPV-16 (31.8%), HPV-31 (22.7%), and HPV-18 (4.6%). In penile cancers, HPV-16 (62.5%) was the most common genotype followed by HPV-33 (25%) and HPV-18 (12.5%). Among anal cancers, the most frequent genotypes were HPV-16 (75%) and HPV-18 (25%). This study is the first report of evidence based oncogenic HPV genotypes in vulva cancers, penile cancers and anal cancers in Myanmar. This research provides the valuable information in understanding the burden of HPV associated cancers of the vulva, penile, and anus in Myanmar and the consideration of the effectiveness of prophylactic HPV vaccination in not only cervical cancer but also non-cervical cancers. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST: No COIs from the authors.


2018 ◽  
Vol 2 (3) ◽  
Author(s):  
Benjamin D Hallowell ◽  
Mona Saraiya ◽  
Trevor D Thompson ◽  
Elizabeth R Unger ◽  
Charles F Lynch ◽  
...  

Abstract Background Human papillomavirus (HPV) genotype influences the development of invasive cervical cancer (ICC); however, there is uncertainty regarding the association of HPV genotype with survival among ICC patients. Methods Follow-up data were collected from 693 previously selected and HPV-typed ICC cases that were part of the Centers for Disease Control and Prevention Cancer Registry Surveillance System. Cases were diagnosed between 1994 and 2005. The Kaplan-Meier method was used to estimate five-year all-cause survival. A multivariable Cox proportional hazards model was used to estimate the effect of HPV genotype on survival after adjusting for demographic, tumor, and treatment characteristics. Results Five-year all-cause survival rates varied by HPV status (HPV 16: 66.9%, HPV 18: 65.7%, HPV 31/33/45/52/58: 70.8%, other oncogenic HPV genotypes: 79.0%, nononcogenic HPV: 69.3%, HPV-negative: 54.0%). Following multivariable adjustment, no statistically significant survival differences were found for ICC patients with HPV 16–positive tumors compared with women with tumors positive for HPV 18, other oncogenic HPV types, or HPV-negative tumors. Women with detectable HPV 31/33/33/45/52/58 had a statistically significant 40% reduced hazard of death at five years (95% confidence interval [CI] = 0.38 to 0.95), and women who tested positive for nononcogenic HPV genotypes had a statistically significant 57% reduced hazard of death at five years (95% CI = 0.19 to 0.96) compared with women with HPV 16 tumors. Few statistically significant differences in HPV positivity, tumor characteristics, treatment, or survival were found by race/ethnicity. Conclusions HPV genotype statistically significantly influenced five-year survival rates among women with ICC; however, screening and HPV vaccination remain the most important factors to improve patient prognosis and prevent future cases.


Sexual Health ◽  
2007 ◽  
Vol 4 (4) ◽  
pp. 305 ◽  
Author(s):  
S. R. Skinner ◽  
S. M. Garland ◽  
I. Denham ◽  
M. O'Sullivan ◽  
R. Waddell ◽  
...  

Objectives: Previous studies with the HPV-16/18 L1 VLP AS04 vaccine have shown 100% efficacy against HPV 16/18 associated persistent infection and CIN in women with no previous exposure to oncogenic HPV. This interim analysis of a phase III, randomized, controlled trial assessed vaccine efficacy against HPV 16/18 associated CIN2+ and persistent infection with oncogenic HPV types in a broad population of women. Methods: Healthy women, aged 15-25 years, with d6 sexual partners and no previous colposcopy were eligible and were randomly allocated to 3 doses of HPV or hepatitis A (control) vaccine at 0, 1, 6 months. Serum antibodies for HPV 16/18 were assessed by ELISA. HPV DNA was detected by PCR on cervical cytology and biopsy. Vaccine efficacy was assessed in women who received at least one vaccine dose, had normal or low-grade cytology and were HPV 16/18 sero- and DNA negative at entry. Additional analyses were undertaken to assign causality where multiple HPV types were present. Immunogenicity was evaluated in a subset of women and safety was assessed in the entire vaccinated cohort. Results: 18729 women from Asia Pacific (34%), Europe (34%), North (16.5%) and Latin America (14.9%) were enrolled. 18525 were included in the cohort for vaccine efficacy analyses. Mean age was 20 years and mean follow up 15 months from dose 1. Most HPV 16/18 infections were detected prior to dose 3 in this analysis. Of 23 CIN2+ lesions associated with HPV 16/18, 14 contained multiple oncogenic HPV types: three showed no preceding infection or E4 gene expression for the relevant HPV vaccine type. Vaccine efficacy according to HPV DNA detected in the lesion was 90.4% (95% CI, 53.4-99.3); after additional analyses for causality assignment, efficacy was 100% (95% CI: 74.2-100). Cross-protection against 6-months infection with HPV-45, -31, -52; and broad protection against 12-month persistent non-16/18 oncogenic HPV infection was also demonstrated. Seroconversion was 99.5% after dose 2 and 3. Safety profiles were comparable between groups. Conclusions: In a broad cohort of women, high vaccine efficacy was observed against CIN2+ caused by HPV-16/18.


2016 ◽  
Vol 2 (3_suppl) ◽  
pp. 18s-19s
Author(s):  
Mu Mu Shwe ◽  
Kyi Kyi Nyunt ◽  
Khin Saw Aye ◽  
Hlaing Myat Thu ◽  
Hla Myat Mo Mo ◽  
...  

Abstract 11 In Myanmar, cervical cancer ranks as the first most frequent cancer among women aged between 15 to 44 years and Human Papillomavirus (HPV) vaccination program is not established yet. Information on HPV genotypes distribution in cervical cancer is crucial to predict the future impact of HPV vaccines. This study aimed to determine the HPV-DNA and genotypes among women with cervical pre-cancer and cancer in Myanmar. A cross-sectional descriptive study was performed in 169 women with cervical neoplasia during 2012 to 2014. After obtaining informed consent, cervical cells were collected from 134 women with cervical intraepithelial neoplasia (CIN) and 35 with squamous cell carcinoma (SCC) of the cervix attending Sanpya General Hospital, Yangon, and Central Women Hospital, Mandalay. HPV-DNA testing and genotyping was performed by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). HR-HPV was identified in CINI (39.3%), CINII (58.6%), CINIII (66.7%), and SCC (77.1%). Overall, the most common genotypes were HPV-16 (68.1%), followed by HPV-31 (16.5%), HPV-18 (7.7%), HPV-58 (6.6%), and HPV-35 (1.1%). Among SCC, HPV-16 was the most common genotype (66.7%) followed by HPV-18 (14.8%), HPV-31 (11.1%), HPV-35 (3.7%), and HPV-58 (3.7%). In CINI, the most common genotype were HPV-16 (69.7%) followed by HPV-31 (21.2%), HPV-18 (6.1%) and HPV-58 (3.0%). In CINII, HPV-16 was most commonly determined (52.9%) followed by HPV-31 (23.5%), HPV-58 (17.6%), and HPV-18 (5.9%). In CINIII, HPV-16 was also the most common genotype (85.7%) followed by HPV-31 (7.1%) and HPV-58 (7.1%). Vaccine preventable genotype, HPV-16 was the most common genotype in Myanmar. This study highlighted that the establishment of National HPV vaccination program is needed to reduce the incidence and mortality of cervical cancer in Myanmar.[Table: see text][Table: see text] AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST: No COIs from the authors.


2009 ◽  
Vol 127 (3) ◽  
pp. 122-127 ◽  
Author(s):  
Denise Rocha Pitta ◽  
Luis Otávio Sarian ◽  
Elisabete Aparecida Campos ◽  
Sílvia Helena Rabelo-Santos ◽  
Kari Syrjänen ◽  
...  

CONTEXT AND OBJECTIVE: Differences in human papillomavirus (HPV) types may correlate with the biological potential and invasion risk of high-grade cervical intraepithelial neoplasia (CIN 2 and CIN 3). The objective of this study was to determine the relationship between different combinations of HPV types and CIN severity. DESIGN AND SETTING: Cross-sectional study, at Universidade Estadual de Campinas (Unicamp). METHODS: Cervical samples from 106 women treated due to CIN 2 (18) or CIN 3 (88) were examined for specific HPV genotypes using Roche Linear Array® (LA-HPV). The proportions of CIN 2 and CIN 3 in groups of women infected with the HPV phylogenetic groups A7 and A9 were compared. Three groups were formed: women with single infections; multiple infections; and the whole sample. RESULTS: Multiple infections were detected in 68 samples (64.7%). The most frequent high-risk genotypes detected (single/multiple) were HPV 16 (57.1%), HPV 58 (24.7%), HPV 33 (15.2%), HPV 52 (13.3%), HPV 31 (10.4%), HPV 51 (7.6%) and HPV 18 (6.6%). Women without infection with HPV species Alpha 9 were less likely to have CIN 3 than were their Alpha 9 HPV-infected counterparts. HPV 16 and/or HPV 18, with or without associations with other viral types, were more frequently found in women with CIN 3 than in those with CIN 2. CONCLUSIONS: The severity of high-grade CIN may be aggravated by the presence of HPV types included in the Alpha 9 phylogenetic classification and by infections including HPV 16 and 18, singly or in combination with other HPV genotypes.


2022 ◽  
Vol 19 (1) ◽  
Author(s):  
Awoke Derbie ◽  
Daniel Mekonnen ◽  
Endalkachew Nibret ◽  
Melanie Maier ◽  
Yimtubezinash Woldeamanuel ◽  
...  

Abstract Background Cervical cancer is caused by infection with high-risk human papillomaviruses (HR-HPVs). It is one of the leading causes of cancer-related deaths in Ethiopia and globally. To develop efficient vaccination and HPV-based cervical cancer screening approaches, data on genotype distribution of HPVs is crucial. Hence, the study was aimed to review HPV genotype distribution in Ethiopia. Methods Research articles were systematically searched using comprehensive search strings from PubMed/Medline and SCOPUS. Besides, Google Scholar was searched manually for grey literature. The last search was conducted on 18 August 2021. The first two authors independently appraised the studies for scientific quality and extracted the data using Excel sheet. The pooled HPV genotype distribution was presented with descriptive statistics. Results We have included ten studies that were reported from different parts of the country during 2005 and 2019. These studies included 3633 women presented with different kinds of cervical abnormalities, from whom 29 different HPV genotypes with a sum of 1926 sequences were reported. The proportion of high-risk, possible/probable high-risk and low-risk HPVs were at 1493 (77.5%), 182 (9.4%) and 195 (10.1%), respectively. Of the reported genotypes, the top five were HPV 16 (37.3%; 95% CI 35.2.1–39.5%), HPV 52 (6.8%; 95% CI 5.8–8.0%), HPV 35 (4.8%; 95% CI 3.9–5.8%), HPV 18 (4.4%; 95% CI 3.5–5.3%) and HPV 56 (3.9%: 95% CI 3.1–4.9%). Some of other HR-HPV groups include HPV 31 (3.8%), HPV 45 (3.5%), HPV 58 (3.1%), HPV 59(2.3%), and HPV 68 (2.3%). Among the high-risk types, the combined prevalence of HPV 16/18 was at 53.7% (95% CI 51.2–56.3%). HPV 11 (2.7%: 95% CI 2.1–3.5%), HPV 42 (2.1%: 95% CI 1.5–2.8%) and HPV 6 (2.1%: 95% CI 1.4–2.7%) were the most common low-risk HPV types. Conclusions We noted that the proportion of HR-HPV types was higher and HPV 16 in particular, but also HPV 52, HPV 35 and HPV 18, warrant special attention in Ethiopian’s vaccination and HPV based cervical screening program. Additional data from other parts of the country where there is no previous HPV genotype report are needed to better map the national HPV genotypes distribution of Ethiopia.


2013 ◽  
Vol 23 (1) ◽  
pp. 148-156 ◽  
Author(s):  
Swee Chong Quek ◽  
Boon Kiong Lim ◽  
Efren Domingo ◽  
Ruey Soon ◽  
Jong-Sup Park ◽  
...  

ObjectiveIndependent, prospective, multicenter, hospital-based cross-sectional studies were conducted across 5 countries in Asia, namely, Malaysia, Vietnam, Singapore, South Korea, and the Philippines. The objectives of these studies were to evaluate the prevalence of human papillomavirus (HPV) types (high risk and others including coinfections) in women with invasive cervical cancer (ICC) and high-grade precancerous lesions.MethodsWomen older than 21 years with a histologic diagnosis of ICC and cervical intraepithelial neoplasia [CIN 2 or 3 and adenocarcinoma in situ (AIS)] were enrolled. Cervical specimens were reviewed by histopathologists to confirm the presence of ICC or CIN 2/3/AIS lesion and tested with short PCR fragment10-DNA enzyme immunoassay-line probe assay for 14 oncogenic HPV types and 11 non-oncogenic HPV types. The prevalence of HPV 16, HPV 18, and other high-risk HPV types in ICC [including squamous cell carcinoma (SCC) and adenocarcinoma/adenosquamous carcinoma (ADC/ASC)] and CIN 2/3/AIS was estimated.ResultsIn the 5 Asian countries, diagnosis of ICC was confirmed in 500 women [SCC (n = 392) and ADC/ASC (n = 108)], and CIN 2/3/AIS, in 411 women. Human papillomavirus DNA was detected in 93.8% to 97.0% (84.5% for the Philippines) of confirmed ICC cases [94.0%–98.7% of SCC; 87.0%–94.3% (50.0% for the Philippines) of ADC/ASC] and in 93.7% to 100.0% of CIN 2/3/AIS. The most common types observed among ICC cases were HPV 16 (36.8%–61.3%), HPV 18 (12.9%–35.4%), HPV 52 (5.4%–10.3%), and HPV 45 (1.5%–17.2%), whereas among CIN 2/3/AIS cases, HPV 16 (29.7%–46.6%) was the most commonly observed type followed by HPV 52 (17.0%–66.7%) and HPV 58 (8.6%–16.0%).ConclusionsThis article presents the data on the HPV prevalence, HPV type distribution, and their role in cervical carcinogenesis in 5 Asian countries. These data are of relevance to public health authorities for evaluating the existing and future cervical cancer prevention strategies including HPV-DNA testing–based screening and HPV vaccination in these Asian populations.


2021 ◽  
Vol 15 (09) ◽  
pp. 1339-1345
Author(s):  
Richard Tagne Simo ◽  
Arsène G Djoko Nono ◽  
Hervet Paulin Fogang Dongmo ◽  
Paul F Seke Etet ◽  
Bertrand Kiafon Fonyuy ◽  
...  

Introduction: Various Human papillomavirus (HPV) types cause cervical cancer, and represent the primary cause of cancer death in Africa and the second cause of most common cancers in Cameroon. Herein, we determined the prevalence of high-risk HPV types in women and associated cervical cytologic abnormalities in Yaounde, Cameroon. Methodology: A cross-sectional study targeting HPV-positive women aged 20 and over was conducted between March and June 2020 at the Saint Martin de Porres’ Health Centre in Yaounde. HPV tests were performed by PCR for detection of HPVs 16, 18, 33, and 45. The test was performed on 616 women using exfoliated cell specimens; then, we processed on cytological diagnosis with Pap smears on HPV positive specimens. Results: The HPV types tested were detected in 137 participants, of which 38.7% with multiple HPV infections, and the remaining part with single HPV infections of type HPV 16 (28.5%), HPV 18 (17.5%), HPV 33 (10.2%), and HPV 45 (5.1%). Cervical cytologic abnormalities were found in 69.34% of participants including: LSIL (49.63%), HSIL (15.32%), ASC-US (3.66%) and AGC (0.73%). Co-infections with HPV 16 and HPV 18 were significantly associated with HSIL (p = 0.001) lesions, while HPV 45 was more common in participants with normal cytology (p = 0.001). Cervical lesion occurrence was significantly associated with the number of sexual partners (p = 0.02) and history of oral contraceptive pill use (p = 0.001). Conclusions: Our results suggest that HPV 16 and 18 are predominant in Yaounde, and are associated with more severe precancerous lesions.


2000 ◽  
Vol 11 (2) ◽  
pp. 80-84 ◽  
Author(s):  
A Wikström ◽  
C Popescu ◽  
O Forslund

The occurrence of human papillomavirus (HPV) among males was analysed with the polymerase chain reaction (PCR) method. Penile brush samples were taken once from 147 males attending for a control or for HPV non-related reasons, and consecutive samples were collected from 88 males re-attending the clinic. Of the males attending once, 13% (19/147) were HPV DNA positive and among the re-attenders 14% (12/88) were initially positive as compared with 33% (29/88) who were positive at least at one visit. Totally, 22 different HPV types were detected of which HPV 16 was most common, found in 6.4% (15/235), followed by HPV 42 found in 3.8% (9/235). Among 14 HPV-positive males with at least one follow-up, 7 had persistent infections with at least one HPV type, and transient HPV types were observed in 9; but in 5 of them new types appeared at follow-up. Among sexually-active males subclinical/latent HPV infection is common and repeated sampling increases its prevalence.


2007 ◽  
Vol 17 (6) ◽  
pp. 1307-1313 ◽  
Author(s):  
S. Y. Tong ◽  
Y. S. Lee ◽  
J. S. Park ◽  
S. E. Namkoong

The clinical implications of specific human papillomavirus (HPV) types in invasive cervical carcinomas are only now beginning to be appreciated. The objective of this study was to determine the clinical implications and prognostic value of the HPV genotype in cervical carcinomas. In this study, we employed an HPV DNA chip to detect the type-specific sequence of HPV from cervical swabs taken from women with biopsy-proven neoplastic lesions of the cervix. We divided the patients into four groups: HPV-negative, HPV-16-related, HPV-18-related, and intermediate risk type–related. Associations with clinicopathologic data (stage, histologic type, lymph node status, parametrial invasion, lymphvascular space invasion, tumor size, vaginal involvement) and overall survival were assessed. HPV DNA was detected in 81.4% of the patients, and 19.0% harbored multiple HPV variants. HPV-16-related was the predominant type and was detected in 47.4% (46/97) of the patients. The HPV-16-related types were detected more frequently in patients with squamous cell carcinomas, whereas the HPV-18-related types were more prevalent in cases of adenocarcinomas and adenosquamous carcinomas (P< 0.05). Otherwise, no significant correlations were detected between the HPV genotype and any other clinicopathologic parameters. After a median follow-up of 30 months, the 5-year survival rate was lower in the HPV-18-related patients, but this difference was not found to be statistically significant, according to the results of the log-rank test. We conclude that neither the presence nor type of HPV DNA bears any prognostic significance in cases of cervical carcinoma.


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