We have amplified by the polymerase chain reaction, cloned, and sequenced genomic segments of 118 human papillomavirus type 16 (HPV-16) isolates from 76 cervical biopsy, 14 cervical smear, 3 vulval biopsy, 2 penile biopsy, 2 anal biopsy, and 1 vaginal biopsy sample and two cell lines. The specimens were taken from patients in four countries-Singapore, Brazil, Tanzania, and Germany. The sequence of a 364-bp fragment of the long control region of the virus revealed 38 variants, most of which differed by one or several point mutations. Phylogenetic trees were constructed by distance matrix methods and a transformation series approach. The trees based on the long control region were supported by another set based on the complete E5 protein-coding region. Both sets had two main branches. Nearly all of the variants from Tanzania were assigned to one (African) branch, and all of the German and most of the Singaporean variants were assigned to the other (Eurasian) branch. While some German and Singaporean variants were identical, each group also contained variants that formed unique branches. In contrast to the group-internal homogeneity of the Singaporean, German, and Tanzanian variants, the Brazilian variants were clearly divided between the two branches. Exceptions to this were the seven Singaporean isolates with mutational patterns typical of the Tanzanian isolates. The data suggest that HPV-16 evolved separately for a long period in Africa and Eurasia. Representatives of both branches may have been transferred to Brazil via past colonial immigration. The comparable efficiencies of transfer of the African and the Eurasian variants to the New World suggest pandemic spread of HPV-16 in past centuries. Representatives of the African branch were possibly transferred to the Far East along old Arab and Indonesian sailing routes. Our data also support the view that HPV-16 is a well-defined virus type, since the variants show only a maximal genomic divergence of about 5%. The small amount of divergence in any one geographic location and the lack of marked divergence between the Tanzanian and Brazilian African genome variants two centuries after their likely introduction into the New World suggest a very slow rate of viral evolution. The phylogenetic tree therefore probably represents a minimum of several centuries of evolution, if not an age equal to that of the respective human races.

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Three hundred fifty albinos in the city of Dar‐es‐Salaam have been registered at the Tanzania Tumor Centre. Their skin changes were followed for at least 2 years. Chronic skin damage was evident in all albinos by the first year of life; by 20 years, the skin of every subject demonstrated subclinical malignant change, and some had clinical epitheliomas. Untreated, the latter tumors become intractable and disseminate, usually causing death in the third or fourth decade of life. Four clinical stages could be identified, each one associated with distinct pathologic changes: Stage 1, erythema; Stage 2, epidermal atrophy with dermal hypertrophy; Stage 3, solar keratosis; and Stage 4, clinical carcinoma (under 3 cm). It was found that clinical Stage 2 only occurs in those skin areas that show evidence of previous Stage 1 change. Similarly, Stage 3 occurs only in areas that have gone through Stages 1 and 2. Stage 4 cancers were only found in those areas that had gone through all of the three prior stages. During the 2‐year period of this study, 104 skin cancers, both early and advanced, were recorded at the albino skin clinic. Thirty‐three of the 104 cancers were advanced (over 4 cm in diameter). The median age of the latter group was 31.0 years. Whereas there was no sex bias in the distribution of clinical cancer, 28 of the 33 advanced cancers were in men. Histologically, the great majority of the advanced tumors were squamous cell carcinomas: 29 of 33. There was one melanoma and three basal cell tumors. The predominant site of advanced cancers in the study group was the head and neck region (30 patients); the other three occurred on the trunk, which is generally covered by clothes.

The presence of HPV-DNA was determined in tumor biopsies of cervical-cancer patients and in cervical swabs of non-cancer patients from Tanzania, East Africa, by Southern blot hybridization and/or PCR. HPV types 16 and 18 were detected in 38% and 32%, respectively, of 50 cervical-carcinoma biopsies. A consensus primer PCR capable of detecting a broad spectrum of HPV types revealed the presence of HPV-DNA in 59% of 359 cervical swabs of non-cancer patients. Type-specific PCR showed that types 16 and 18 accounted for 13.2% and 17.5%, respectively, of all HPV infections. Therefore we concluded that HPV 18 is more prevalent in Tanzania than in any other geographical location so far reported. The strongest risk factors for the presence of any HPV-DNA in the 359 female non-cancer patients were young age and HIV infection. The epidemiology of HPV types 16 and 18 was found to differ from that of other HPV types, being associated in univariate analysis with trichomonas vaginalis infection, martial status (single/divorced), age at first intercourse, and young age at menarche. However, young age at menarche accounted for most of the effects of all other, variables in multivariate analysis. Of the non-cancer patients, 12.8% had antibodies against HIV I (no patient being severely symptomatic), and HIV infection was highly correlated with the presence of HPV-DNA, especially types 16 and 18. While HPV-DNA of any type was detectable 1.4-fold more often in HIV-positive patients than in HIV-negative patients, evidence of an infection with HPV types 16 or 18 was found 2.2-fold more often in the HIV-positive patients. The HIV-positive women did not show an increased rate of cervical cytological abnormalities as assessed by PAP staining of a single cervical smear, the overall rate of abnormalities being 2.8%. Furthermore, the age-adjusted prevalence of HIV antibodies was found to be considerably lower in 270 cervical-carcinoma patients (3% HIV-positive) in comparison with non-cancer patients. Thus there was no association observable between the prevalence of HIV infections and the frequency of cervical cytological abnormalities or cervical cancer in the setting of this cross-sectional study.