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A novel set of polymerase chain reaction (PCR) primers , designated SPF1 and SPF2 and located in the L1 region , was developed for universal detection of human papillomavirus (HPV). A short PCR fragment (SPF) of only 65 pb was synthesized. SPF amplimers were detected in a microtiter-based hybridization system , using a mixture of oligonucleotide probes. The SPF system allowed detection of at least 43 different HPV genotypes. The clinical performance of the novel SPF system was assessed in three different patient groups. 1) Analysis of 534 cervical scrapes , obtained from treated patients , showed that the detection rate in 447 (83.7%) scrapes with normal cytology was significantly higher using the SPF system as compared with the universal primer set GP5؉/6؉ (P < 0.001). 2) The SPF assay detected HPV DNA in 299 (98.4%) of 304 scrapes with cytological dyskaryosis. 3) The SPF system detected HPV DNA in 100% of 184 formalin-fixed, paraffin-embedded cervical carcinoma specimens. In conclusion , the novel SPF system permitted universal and highly sensitive detection of HPV DNA in diverse clinical materials and may improve the molecular diagnosis and epidemiology of this important virus. (Am J Pathol 1998, 153:1731-1739)Cervical cancer is the second most important cause of cancer-related mortality in women after breast cancer, 1 annually affecting an estimated 500,000 women worldwide. 2 Smoking, age of first sexual contact, number of sexual partners, and immunological status have been identified as significant risk factors for cervical carcinoma. [3][4][5][6] Infection with human papillomavirus (HPV) also is considered to be an important risk factor. 7,8 HPV is an epitheliotropic virus and contains a circular doublestranded DNA genome of approximately 7900 bp. To date, at least 77 distinct HPV genotypes have been described that can be classified into a cutaneous and a mucosal group, as established by their associated clinical manifestations. 8 Among the mucosal genotypes that infect the anogenital tract, potentially high-risk HPV genotypes 16,18,31,33,35,39, 45, 51, 52, 56, 58, 66, and 69 have been defined based on their prevalence in cervical intraepithelial neoplasia (CIN) lesions and cervical carcinomas. 8 The HPV genotypes 6,11,34,40, 42, 43, 44, 53, 54, 55, 59, 61, 62, 67, 68, 71, and 74 are classified as putative low-risk factors. By definition, infection with high-risk HPV genotypes favors an increased risk for cancer. 9 -11 However, the distinction between high-risk and low-risk genotypes is a moot point as low-risk HPV genotypes have also been found in carcinomas. 9 As HPV cannot be cultured in vitro and serological assays are still ineffective, diagnosis of HPV injury is based on the use of molecular tools. Direct dot-spot detection and in situ hybridization assays have been described, 12,13 but these methods are tedious and appear to lack sensitivity and specificity. DNA amplification methods, such as the polymerase chain reaction (PCR), permit more sensitive detection of the viral DNA. Besides type-specif...

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BackgroundHuman papillomavirus (HPV) infection, particularly with type 16, causes a growing fraction of oropharyngeal cancers, whose incidence is increasing, mainly in developed countries. In a double-blind controlled trial conducted to investigate vaccine efficacy (VE) of the bivalent HPV 16/18 vaccine against cervical infections and lesions, we estimated VE against prevalent oral HPV infections 4 years after vaccination.Methods and FindingsA total of 7,466 women 18–25 years old were randomized (1∶1) to receive the HPV16/18 vaccine or hepatitis A vaccine as control. At the final blinded 4-year study visit, 5,840 participants provided oral specimens (91·9% of eligible women) to evaluate VE against oral infections. Our primary analysis evaluated prevalent oral HPV infection among all vaccinated women with oral and cervical HPV results. Corresponding VE against prevalent cervical HPV16/18 infection was calculated for comparison. Oral prevalence of identifiable mucosal HPV was relatively low (1·7%). Approximately four years after vaccination, there were 15 prevalent HPV16/18 infections in the control group and one in the vaccine group, for an estimated VE of 93·3% (95% CI = 63% to 100%). Corresponding efficacy against prevalent cervical HPV16/18 infection for the same cohort at the same visit was 72·0% (95% CI = 63% to 79%) (p versus oral VE = 0·04). There was no statistically significant protection against other oral HPV infections, though power was limited for these analyses.ConclusionsHPV prevalence four years after vaccination with the ASO4-adjuvanted HPV16/18 vaccine was much lower among women in the vaccine arm compared to the control arm, suggesting that the vaccine affords strong protection against oral HPV16/18 infection, with potentially important implications for prevention of increasingly common HPV-associated oropharyngeal cancer.ClinicalTrials.gov, Registry number NCT00128661

Coinfecting HPV genotypes occur at random and lead to cervical disease independently.

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The Costa Rica HPV16/18 Vaccine Trial (CVT) showed that four-year vaccine efficacy against 12-month HPV16/18 persistent infection was similarly high among women who received one, two, or the recommended three doses of the bivalent HPV16/18 L1 virus-like particle (VLP) vaccine. Live-attenuated viral vaccines, but not simple-subunit vaccines, usually induce durable lifelong antibody responses after a single dose. It is unclear whether noninfectious VLP vaccines behave more like live-virus or simple-subunit vaccines in this regard. To explore the likelihood that efficacy will persist longer term, we investigated the magnitude and durability of antibodies to this vaccine by measuring HPV16-and HPV18-specific antibodies by VLP-ELISA using serum from enrollment, vaccination, and annual visits through four years in four vaccinated groups; one-dose (n ¼ 78), two-doses separated by one month (n ¼ 140), two doses separated by six months (n ¼ 52), and three scheduled doses (n ¼ 120, randomly selected). We also tested enrollment sera from n ¼ 113 HPV16-or HPV18 L1-seropositive women prevaccination, presumably from natural infection. At four years, 100% of women in all groups remained HPV16/18 seropositive; both HPV16/18 geometric mean titers (GMT) among the extended two-dose group were non-inferior to the three-dose group, and ELISA titers were highly correlated with neutralization titers in all groups. Compared with the natural infection group, HPV16/18 GMTs were, respectively, at least 24 and 14 times higher among the two-dose and 9 and 5 times higher among one-dose vaccinees. Antibody levels following one-dose remained stable from month 6 through month 48. Results raise the possibility that even a single dose of HPV VLPs will induce long-term protection. Cancer Prev Res; 6(11); 1242-50. Ó2013 AACR.