DNA from one biopsy sample of invasive cancer of the cervix contained sequences hybridizing with human papillomavirus (HPV) type 11 DNA only under nonstringent conditions. This DNA was molecularly cloned in A phage. Under stringent conditions of hybridization it cross-hybridized to a minor extent (less than 0.1%) with HPV types 10, 14, and 15 and showed no homology with DNA of other human HPV types. We therefore propose to designate it tentatively as HPV 16. HPV 16 DNA was used as a probe to test additional cancer biopsy samples from cervical, vulval, and penile cancer, as well as benign genital warts (condylomata acuminata) and cervical dysplasias for the presence of homologous sequences. In 61.1% (11/18)

DNA of a new papillomavirus type was cloned from a cervical carcinoma biopsy. Two EcoRI clones of 7.8 and 6.9 kb in length were obtained, the latter contained a 900‐bp deletion. The BamHI fragments of both clones were used to characterize the DNA. It represents a distinct type of papillomavirus as determined by its size, its cross‐hybridization with DNA of other papillomavirus types under conditions of low stringency only, the co‐linear alignment of its genome with HPV 6 and HPV 16 prototypes and its occasional occurrence as oligomeric episomes. We tentatively propose to designate it as HPV 18. DNA hybridizing with HPV 18 under stringent conditions was detected in 9/36 cervical carcinomas from Africa and Brazil, in 2/13 cervical tumors from Germany and 1/10 penile carcinomas. Benign tumors (17 cervical dysplasias, 29 genital warts), eight carcinomata in situ and 15 biopsies of normal cervical tissue were devoid of detectable HPV 18 DNA. HPV 18‐related DNA was found, however, in cells of the HeLa, KB and C4‐1 lines all derived from cervical cancer. The state of the viral DNA was investigated in four cervical cancer biopsies. The data reveal that the DNA might be integrated into the host cell genome. One tumor provided evidence for head to tail tandem repeats some of which persisted as circular episomes.

Human genital tumors as well as recurrent laryngeal papillomas were analyzed for the presence of human papil, lomavirus (HPV)6 and HPV 11 sequences. HPV 11 DNA was found in 7 of 14 laryngeal papillomas; in the 7 other tumors no HPV DNA was demonstrated. HPV 11 DNA was also found in all five atypical condylomata of the cervix included in this study. Condylomata acuminata mainly contained HPV 6 DNA. From 63 biopsy specimens, 41 clearly harbored HPV 6 DNA and 13 harbored HPV 11 DNA. In three tumors accurate typing was impossible, and in six additional ones neither HPV 6 nor .HPV 11 DNA could be demonstrated. The data support a genital origin of laryngeal papillomavirus infections. In 4 of 24 malignant tumors, HPV 11 DNA or related sequences were demonstrated; 2 of the 4 were biopsy specimens from invasive cancer, and the other 2 originated from carcinomata in situ. A possible role of this or related papillomavirus types in the induction of malignant genital. tumors remains to be elucidated.

BackgroundPap cytology is known to be more specific but less sensitive than testing for human papillomavirus (HPV) for the detection of high-grade cervical intraepithelial neoplasia (CIN2+). We assessed whether p16/Ki-67 dual-stained cytology, a biomarker combination indicative of transforming HPV infections, can provide high sensitivity for CIN2+ in screening while maintaining high specificity. Results were compared with Pap cytology and HPV testing.MethodsA total of 27349 women 18 years or older attending routine cervical cancer screening were prospectively enrolled in five European countries. Pap cytology, p16/Ki-67 immunostaining, and HPV testing were performed on all women. Positive test results triggered colposcopy referral, except for women younger than 30 years with only positive HPV test results. Presence of CIN2+ on adjudicated histology was used as the reference standard. Two-sided bias-corrected McNemar P values were determined.ResultsThe p16/Ki-67 dual-stained cytology positivity rates were comparable with the prevalence of abnormal Pap cytology results and less than 50% of the positivity rates observed for HPV testing. In women of all ages, dual-stained cytology was more sensitive than Pap cytology (86.7% vs 68.5%; P < .001) for detecting CIN2+, with comparable specificity (95.2% vs 95.4%; P = .15). The relative performance of the tests was similar in both groups of women: younger than age 30 and 30 years or older. HPV testing in women 30 years or older was more sensitive than dual-stained cytology (93.3% vs 84.7%; P = .03) but less specific (93.0% vs 96.2%; P < .001).ConclusionsThe p16/Ki-67 dual-stained cytology combines superior sensitivity and noninferior specificity over Pap cytology for detecting CIN2+. It suggests a potential role of dual-stained cytology in screening, especially in younger women where HPV testing has its limitations.

32P-labelled DNA of HPV 16 which has been isolated and molecularly cloned from a cervical carcinoma (Dürst et al., 1983) was used to screen the cellular DNAs obtained from 20 different biopsies of Morbus Bowen or Bowenoid papulosis, respectively, by Southern blot analysis. Under conditions of differing stringency for the hybridization, HPV 16 DNA or related sequences were identified in 6 out of 10 cases of Morbus Bowen (4 out of 5 from a genital localization) and in 8 out of 10 biopsies from Bowenoid papulosis. One additional case of the latter disease contained DNA sequences of an HPV type not yet classified. There is evidence for the presence of another HPV DNA in two of the HPV-16-positive tumors. A large number of normal genital tissue samples were negative for HPV DNA.