Anogenital warts or condylomata acuminata are virus-induced skin papillomas of the external genitalia and perianal areas, caused by certain types of human papilloma viruses (HPVs). Celsus (1st century AD) accurately described penile warts, clearly associating this condition with intercourse. However, while the literary records of venereal warts certainly go back to at least two millennia, up until now we have been unable to find any report of such papillomas and viruses in palaeopathological literature.1
The Basilica of San Domenico Maggiore, which dates back to the beginning of the 14th century, is one of the largest and important churches in Naples. The monumental sacristy of the Basilica contains, in a suspended gateway close to the vault, 38 wooden sarcophagi with the mummies of ten Aragonese kings and other Neapolitan nobles who died in the 15th and 16th centuries. The study of these mummies produced very important results for palaeopathology, palaeovirology and palaeoncology.2
Mary of Aragon (1503-1568) is a typical example of Renaissance noblewoman, whose beauty attracted the admiration of the humanists. She was member of the literary circle of Ischia, founded by the Renaissance poetess Victoria Colonna, friend of Michelangelo. Her artificial mummy, still wearing precious Renaissance clothing and showing asymmetrical swelling of the lower limbs, by impressive oedema, revealed syphilitic gumma of the skin with typical treponemes.2 For this reason we decided to submit it to new investigations for other sexually transmitted diseases.
Further examination of the mummy evidenced, in the right paravulvar region, a large pedunculated branching skin neoformation (about 3×12 mm) which, rehydrated by Sandison’s solution, was submitted to histology with Masson’s trichromic staining (details from G. F.). Light microscopy evidenced an exophytic papillary skin lesion with thickened epidermis and less dense internal tissue with dilated vessels. These macroscopic and histological aspects suggested condyloma acuminatum,3 a papillomavirus-induced squamous lesion also called “venereal wart”.
In order to detect the presence of HPV, DNA extracted from a single 5 mm paraffin-embedded tissue was amplified with L1 consensus primers GP5+/GP6+, promoting the amplification of a 141 base-pair sequence from 25 distinct genital HPVs4 (details from G. F.). The amplified DNA fragment was employed for direct hybridization with oligonucleotides HPV 6, 11, 16, 18, 33, revealing the presence of HPV 18, a virus with high oncogenic potential. To confirm the results, the amplified fragments were cloned and sequenced. Automated sequencing of several clones confirmed the infection of HPV 18 and also revealed the presence of JC9813 DNA, a putative novel HPV with low oncogenic potential, recently discovered.5
The diagnosis of condyloma acuminatum in palaeopathology is important because the type HPV 18 plays a major role in the pathogenesis of some epithelial cancers of the female genital tract3 and also because this discovery, representing the first molecular diagnosis of HPV in mummies, could pave the way for further research on the secular evolution of these viruses.
Gino Fornaciari, Katia Zavaglia, Gloria Bertacca, Laura Giusti, Ivo Marchetti, *Claudia Vultaggio, Rosalba Ciranni
Department of Oncology, Transplants and Advanced Technologies in Medicine,
Section of History of Medicine and Paleopathology; Laboratory of Molecular Pathology; Section of Cytopathology, University of Pisa, Via Roma 57, 56126 Pisa, Italy; and *Department of Regional Cultures, 2nd University of Naples, Italy
(e-mail: g.fornaciari@med.unipi.it)
1 Aufderheide AC. The scientific study of mummies. Cambridge: Cambridge University Press, 2002.
2 Fornaciari G. Italian mummies. In: Cockburn A, Cockburn E, Reyman TS eds. Mummies, Disease and Ancient Cultures. Cambridge: Cambridge University Press, 1998: 266-281.
3 Kurman RJ, Norris HJ, Wilkinson EJ. Tumors of the cervix, vagina and vulva. Rosai J ed. Atlas of tumor pathology. Washington: Armed Forces Institute of Pathology, 1992: 180-182.
4 Husnjak K, Grce M, Magdic L, Pavelic K. Comparison of five different polymerase chain reaction methods for detection of human papillomavirus in cervical cell specimens. J Virol Methods. 2000; 88: 125-34.
5 Feoli-Fonseca JC, Oligny LL, Filion M, Simard P, Russo PA, Yotov WV. A putative novel human papillomavirus identified by PCR-DS. Biochem Biophys Res Commun 1998; 250: 63-67.
