Immunology of HPV
There are many viruses to which we readily develop immunity, such as the 300+ rhinoviruses (cold viruses), measles, polio, mumps, chickenpox, and HPV. However, HPV and several viruses manage to avoid the immune system in some people. The viruses avoid the humoral response and the cellular response, the B-cells and the T-cells, respectively. Anything that supports the immune system will naturally help the body develop immunity to viruses. When immunity to HPV occurs, the body is no longer infected or contagious. As a result of immunity, the signs and symptoms clear, and the same HPV type can generally no longer infect the individual.
The only reason people would say that HPV cannot be cured is because they have simply decided to believe that it cannot. Certainly in some people it cannot be cured, but in most it can be. If we use the HPV test to determine if someone has HPV, then we should use the HPV test to determine if someone does not have HPV. Otherwise, we would be using the HPV test to prove that someone has HPV, but saying that if the test is negative then it means nothing. In fact, however, everyone does use the HPV test to determine if a patient is “HPV negative.” And, even if a person has a low HPV antibody titer (concentration) per a blood analysis, this does not mean that the person is infected. If you had a polio vaccination or a smallpox vaccination, you probably have a very low titer of smallpox antibody or polio antibody. But, you would not assume that you are infected with polio or smallpox. Quite the contrary, you would assume that you have a fairly good immunity to those diseases.
Eur J Dermatol 1998 Oct-Nov;8(7 Suppl):8-12; discussion 20-2:
The immunology of genital human papilloma virus infection.
Stanley M. Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, England.
"This paper reports a presentation by Margaret Stanley, Reader in Epithelial Biology, at the University of Cambridge, in which she reviews the evidence to date regarding the immunology of human papilloma virus (HPV) infection in genital warts.
In this she explains that investigations into the immunology of genital wart infections indicate that the replication cycle of papilloma viruses is tightly linked to keratinocyte differentiation - a strategy for immune evasion. While the papilloma virus infects primitive basal cells, viral replication and viral assembly are confined to differentiating superficial epithelial cells. Viral replication and release are confined to cells destined for death and are not associated with inflammation.
Such findings suggest that the immune system is ignorant or indifferent to the infection. Evidence from regressing genital warts in humans and animal models suggests that HPV is a cell-mediated immune response of the Th1 type offering a strategy for immunotherapy in benign disease. This is supported by evidence from trials with immunomodulatory agents.
While strategies to elicit cytotoxic responses are required for malignant HPV associated lesions, the problems of immune evasion associated with these approaches should not be underestimated. Present optimal therapeutic strategies for genital human papilloma viruses infection would therefore appear to require the induction of a virus specific immune response, either by immunomodulatory agents and/or immunization with the relevant viral antigens."
Am J Obstet Gynecol 1996 Mar;174(3):937-42:
Conization for cervical intraepithelial neoplasia is followed by disappearance of human papillomavirus deoxyribonucleic acid and a decline in serum and cervical mucus antibodies against human papillomavirus antigens.
Elfgren K, Bistoletti P, Dillner L, Walboomers JM, Meijer CJ, Dillner J. Department of Obstetrics and Gynecology, Huddinge University Hospital, Sweden.
"Objective: Our purpose was to investigate whether conization for cervical intraepithelial neoplasia eliminates human papillomavirus deoxyribonucleic acid and effects the levels of serum and cervical mucus antibodies against human papillomavirus antigens.
Study design: Analysis of paired cervical brush and serum samples taken from 23 women with cervical intraepithelial neoplasia before and 16 to 27 months after conization was performed for presence of human papillomavirus deoxyribonucleic acid by polymerase chain reaction and for human papillomavirus antibodies by enzyme-linked immunosorbent assay.
Results: Four women had recurrent cervical intraepithelial neoplasia, whereas 19 women were disease free. Eighteen of 23 women were positive for human papillomavirus deoxyribonucleic acid before treatment. At follow-up only the 4 women with recurrent cervical intraepithelial neoplasia were positive. Serum immunoglobulin G levels and A levels and immunoglobulin A levels in cervical mucus against most of the tested human papillomavirus antigens had declined at follow-up.
Conclusions: Human papillomavirus deoxyribonucleic acid was regularly eliminated and human papillomavirus antibody levels, especially local immunoglobulin A, declined after efficient treatment, suggesting that conization may be effective for treating the underlying human papillomavirus infection."
Gynecol Oncol 1999 Feb;72(2):199-201:
Prediction of recurrent and residual cervical dysplasia by human papillomavirus detection among patients with abnormal cytology.
Bollen LJ, Tjong-A-Hung SP, van der Velden J, Mol BW, ten Kate FW, ter Schegget J, Bleker OP. Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
"To determine the discriminative capacity of human papillomavirus (HPV) DNA testing for recurrent and residual cervical dysplasia, 43 patients with abnormal cytology after treatment for cervical dysplasia were tested for the presence of HPV DNA by PCR. An endocervical curettage was performed in all patients for histological examination. Sixteen of the 43 patients showed moderate or severe dysplasia.
The HPV test was positive in all 16 patients with recurrent or residual dysplasia and negative in 12 of the 27 patients without dysplasia. The sensitivity and specificity of the HPV test were 100 and 44%, respectively. The likelihood ratio of a positive HPV test was 1.8, whereas a negative HPV test had a likelihood ratio of 0.12. Testing for the presence of HPV has the potential to select patients without recurrent or residual cervical dysplasia who have an abnormal cytological smear.
This may have clinical implications, since unnecessary diagnostic conizations may be avoided in patients with abnormal cytology after treatment for cervical dysplasia and a negative HPV test."
Clin Immunol 1999 Dec;93(3):302-11:
Recurrent respiratory papillomatosis: altered CD8(+) T-cell subsets and T(H)1/T(H)2 cytokine imbalance.
Bonagura VR, Hatam L, DeVoti J, Zeng F, Steinberg BM. Department of Pediatrics, Schneider Children's Hospital, Long Island Jewish Medical Center, 269-01 76th Avenue, New Hyde Park, New York 11040, USA.
"Human papillomaviruses (HPVs) cause benign papillomas and squamous cell carcinomas in the genital and respiratory tracts. Recurrent respiratory papillomas (RRP) generate a high level of morbidity and significant mortality because of their location, resistance to treatment, and relentless recurrence that can vary in frequency in a given patient and between patients.
We have found that T-cells from these patients, when exposed to or isolated from autologous papilloma tissue, have an elevated percentage of CD8(+), CD28(-) T-cells, and that T-cells from many of these patients express an increase in T(H)2-like cytokine mRNA in response to autologous papilloma tissue. Furthermore, both of these immunologic findings correlate with disease severity.
These observations suggest that patients with RRP, and possibly others with refractory HPV-induced lesions, are unable to manage their disease with an appropriate and effective HPV-specific, T-cell response. This immune imbalance may be responsible for the development and severity of HPV-induced respiratory papillomatosis."
Vet Immunol Immunopathol 2000 Feb 25;73(2):101-27:
The immunology of animal papillomaviruses.
Nicholls PK, Stanley MA. Department of Pathology, University of Cambridge, UK.
"Papillomaviruses are species- and tissue-specific double-stranded DNA viruses. These viruses cause epithelial tumors in many animals, including man.
Typically, the benign warts undergo spontaneous, immune-mediated regression, most likely effected by T-cells (especially CD4, but also CD8 subsets), whereas humoral immunity can prevent new infections. Some papillomavirus infections fail to regress spontaneously and others progress to malignant epithelial tumors. Additionally, the impact of these lesions is greater in immunosuppressed individuals.
Many therapies are ineffective, and there is much interest in the potential for immunological intervention in papillomavirus infections of man and animals. Vaccination can be achieved with 'live' virus, formalin-inactivated virus, synthetic virus-like particles, and DNA vaccination. There has been much recent progress in the development of such vaccines for papillomavirus infections in the rabbit, ox and dog. Success in these animal models suggests that similar approaches may prove useful for prophylactic or therapeutic vaccination against the important human papillomaviruses involved in the development of cutaneous and anogenital warts, laryngeal papillomatosis, and cervical cancer."