Latent Human Papillomavirus Research Articles

The potential impact of HPV-16 reactivation on prevalence in older Australians.

BackgroundSome regional cross-sectional human papillomavirus (HPV) DNA prevalence data show an increase in prevalence in older women, the reasons for which are as yet unknown. A recently published study suggests that the increase may be at least partly due to reactivation of latent HPV in menopausal women.MethodsWe developed a dynamic mathematical model of HPV-16 transmission to estimate the key consequences of hypothetical HPV-16 reactivation in the Australian heterosexual population. We only consider a worst case scenario with regard to reactivation in the Australian setting when all women who are latently infected reactivate and, wherever feasible, we choose model parameter values which may lead to a more pronounced reactivation. The ongoing National HPV vaccination program covering both women and men is incorporated in the model.ResultsWe estimate that about 1 in 10 women and men who appear to have cleared HPV-16 infection may be latently infected. The prevalence of HPV-16 in older Australian women will increase by a factor of up to 3.1 between now and 2025 which will be accompanied by an increase by a factor of around 1.9 in older men. However, the long-term impact of the HPV vaccination is not significantly altered by reactivation.ConclusionsIf the reactivation hypothesis we consider is substantiated, the public health response should be focused on further improvement of cervical screening coverage for older women. Our study also highlights the urgent need for surveillance of HPV prevalence in older Australians.

Detection of oncogenic genital human papillomavirus (HPV) among HPV negative older and younger women after 7 years of follow-up

The knowledge on risk factors of being human papillomavirus (HPV)-positive among older women is sparse. The aim was to determine the frequency of oncogenic HPV appearance after 7 years among initially HPV-negative women and to examine potential risk factors that influence the occurrence of HPV in older women using multiple logistic regression. For comparison, a younger cohort of women examined under identical study settings was included. This prospective cohort study comprised 1,577 older women (age 40-50 at enrolment) and 2,920 women aged 22-32. Participants were interviewed and underwent a gynecological examination at two time points (7 years apart). Cervical samples were tested for HPV using Hybrid Capture 2 (HC2) and only women who tested HC2-negative at baseline were included. The HPV prevalence among older and younger women was 6.4% and 10.7%, respectively, and there was no "second peak" observed among older women. Recent sexual partners were a strong determinant of HPV appearance irrespective of age. Lifetime number of sexual partners was a significant risk factor for HPV appearance among older women, even after adjustment for recent sexual behavior. In addition, menopause was associated with a non-significantly increased risk of HPV appearance at follow-up. In conclusion, appearance of HPV in previously HPV-negative older women may be due to both recent sexual behavior and previous exposure that is, reactivation of a latent HPV infection.

PCR based detection of HPV 16 and 18 genotypes in normal oral mucosa of tobacco users and non-users

There is increasing evidence of a causal association between human papillomavirus (HPV) and oral squamous cell carcinoma (OSCC). Several studies have shown that HPV is associated with increased risk of oral cancer independent of exposure to tobacco and alcohol. The association is valid for HPVs 16 and 18, which generally are considered high risk types, because they have been detected in oral dysplastic lesions and cancers. We determined the baseline prevalence of HPVs 16 and 18 in normal oral mucosa of individuals with and without tobacco habit. PCR was used for DNA collected by oral smears to detect HPV 16/18 DNA in normal oral mucosa of 60 healthy individuals who were assigned to two groups of 30 subjects each. One group had a tobacco habit, the other did not. The tobacco user group comprised individuals who were tobacco chewers only. Sixty-five percent of individuals were positive for HPV 16/18 DNA, but HPV 16/18 positivity was less in individuals with tobacco habit than in those without tobacco habit. No significant association was found between the presence of HPVs and gender, age or duration of chewing habit, or between groups with and without a tobacco habit. We propose that HPVs16 and 18 commonly are present in normal oral mucosa and emphasize the importance of distinguishing clinical, subclinical and latent HPV infections when investigating HPVs and OSCC.

Ileostomy-Associated Chronic Papillomatous Dermatitis Showing Nevus Sebaceous–Like Hyperplasia, HPV 16 Infection, and Lymphedema

Chronic papillomatous dermatitis (CPD) is a stoma site complication due to chronic irritant contact dermatitis. Papillomatosis can also arise in the setting of human papillomavirus (HPV) infection or chronic lymphedema (elephantiasis). Herein, we report the case of a 57-year-old female who presented with a papillomatous growth surrounding a loop ileostomy suspected to be recurrent ovarian serous carcinoma. Excisional biopsy demonstrated nevus sebaceous (NS)-like organoid hyperplasia with koilocytes overlying a dermal scar that exhibited lymphangiectases. Polymerase chain reaction and sequencing for HPV DNA detected HPV 16. In situ hybridization for high-risk HPV DNA showed punctate nuclear pattern in the keratinocytes populating the NS-like hyperplasia indicating integrated HPV 16 DNA. No recurrence has been observed 11 months postexcision. Reports of CPD have documented a spectrum of reactive epidermal hyperplasias including pseudoepitheliomatous, verrucous, papillomatous, syringofibroadenomatous, and rudimentary follicular hyperplasias. HPV DNA has been detected in 3 of 4 CDP cases tested to date and in authentic NS. We postulate that localized lymphedema secondary to scarring coupled with chronic epidermal irritation and inflammation allowed for latent HPV infection to manifest as CPD with NS-like cutaneous hyperplasia.

Condyloma Acuminate and Increase in the Number of Human Immunodeficiency Virus-Positive Patients

See Article on Page 294-298 Condyloma acuminata arising from human papillomavirus (HPV) infection may cause anal squamous cell cancer and can have a recurrence rate of up to 50% of patients after surgical treatment because surgery cannot control latent HPV infection in surrounding tissue [1]. Therefore, trials using interferon, imiquimod, 5-fluorouracil, vaccine and natural products have been performed to reduce the recurrence rate. That the immune function of the host is important to the recurrence of condyloma is supported by the higher recurrences in patients with immune-suppressants and with human immunodeficiency virus (HIV) infection and by condyloma acuminate being a viral infection [2]. The incidence of HPV infection is more than twice in homosexual man than in others, and anal condyloma increases the incidence of anal cancer; hence, anal cancers are increasing in men who have sex with men [3]. With the increases in homosexuality and homosexual marriage, anal condyloma has become a disease deserving attention. Anal condylomas have more dysplasia in homosexual man and a more frequent neoplastic process in HIV-positive patients [4, 5]. Moreover, frequent multiple infections of oncogenic HPV strains such as HPV-type 16 or 18 are seen in HIV-positive patients [6]. Highly active antiretroviral therapy is thought by some researchers to contribute to reduce morbidity and mortality due to HIV infection, resulting in a decreased incidence of HPV infection and anal cancer while other researchers suggest that prolonged survival of HIV-positive patients may increase the prevalence of anal cancers [7]. Few data exist on the incidence of anal condyloma and associated anal squamous cell cancer in Korea. However, the increases in the number of HIV-positive patients and in their survival [8] will eventually make condyloma acuminata and associated anal cancer an important issue. As uterine cervical cancer, a typical cancer caused by HPV infection, diminishes in incidence and mortality because of publicity and education, the time to start surveillance and to increase education to prevent and to reduce the incidence of anal cancer due to HPV infection has arrived.

Constitutive Overexpression of the Oncogene Racl in the Airway of Recurrent Respiratory Papillomatosis Patients Is a Targetable Host-Susceptibility Factor

Recurrent respiratory papillomatosis (RRP) is caused by human papillomaviruses (HPVs), primarily types 6 and 11. The disease is characterized by multiple recurrences of airway papillomas, resulting in high levels of morbidity and significant mortality. The prevalence of latent HPV in the larynx of the general population is much greater than the prevalence of RRP, suggesting a host-susceptibility factor for disease. We report that the oncogene Rac1 and its downstream product cyclooxygenase-2 (COX-2) are both constitutively expressed at high levels throughout the airway of these patients, independent of active HPV infection. Use of the COX-2 inhibitor celecoxib in primary papilloma cell culture resulted in the downregulation of HPV transcription. Furthermore, a proof-of-principle study treating three patients with severe RRP with celecoxib resulted in remission of disease in all cases. Therefore, we have identified the first pharmacologically targetable host-susceptibility pathway that contributes to RRP recurrence.

Tonsil T Cell Immunity to Human Papillomavirus in the Absence of Detectable Virus in Healthy Adults

Human papillomavirus (HPV) is known to infect the epithelium of the upper aerodigestive tract; however, major questions regarding prevalence and persistence of infection, and their relation to local immune response, remain unanswered. To evaluate the tonsil T cell immune response to HPV and compare this to the frequency of detectable virus at this site. A cross-sectional study of cancer-free adults undergoing routine tonsillectomy. Mucosal immune responses to recombinant HPV16 L2E6E7 and HPV6 L2E7 antigens were measured by tonsillar T-lymphocyte proliferation assay in 13 subjects. HPV deoxyribonucleic acid (DNA) was assessed by PCR and reverse line-blot hybridization in an expanded population of 44 subjects. Proliferative T-cell responses to HPV16 and HPV6 were identified in all patients. The presence of a CD45RO+ T cell population responsive to HPV6 L2E7 was confirmed in three of six subjects tested. There were no CD45RO+ responses to HPV16 L2E6E7 and no evidence of current or latent HPV infection of the tonsil. T cell memory to human papillomavirus can be identified in tonsil tissue from an adult population in the absence of concurrent HPV infection. How novel HPV vaccines might augment this preexisting cell-mediated immunity is an essential area for investigation.

Local expression of TAP-1 and MHC-I molecules and their relationship in condyloma acuminatum

Condyloma acuminatum (CA), caused by human papillomavirus (HPV), is characterized by a variable clinical course that can include significant morbidity, frequent disease recurrence and occasional oncogenicity. Effective CD8+ T-cell-mediated clearance of HPV-infected cells may be defective in patients with CA, leading to recurrent disease and failure to suppress latent HPV reactivation. The pathogenesis responsible for CA and the persistence of latent HPV infection remain unknown. To determine whether expression of transporters associated with antigen processing 1 (TAP-1) and the major histocompatibility complex class I (MHC-I) is involved in HPV immune escape. In this present study, we compared 31 CA lesions with 30 normal prepuces by immunohistochemistry and reverse transcription PCR for their expressions of TAP-1 and MHC-I. Expressions of TAP-1 and MHC-I were significantly reduced in CA tissue biopsies compared with normal prepuces. There was a statistically significant positive correlation between expressions of TAP-1 and MHC-I in CA lesions. Furthermore, we found that TAP-1 mRNA was significantly reduced in CA lesions compared with those in normal prepuces. These results suggest that HPV may evade immune recognition by downregulating MHC-I cell surface expression via decreased TAP-1 levels.

Detection of human papillomavirus in organs of upper genital tract in women with cervical cancer

In this study, we evaluated the presence of human papillomavirus (HPV) DNA in organs of the female upper genital tract, using nine hysterectomy and salpingo-oophorectomy specimens affected by HPV-positive invasive cervical carcinomas, to establish if cervical HPV infection can spread to upper tracts of the female genital system. HPV DNA was evaluated by polymerase chain reaction (PCR) in all cervical carcinomas as well as in all tracts of the genital system. Then, these data were compared with the results obtained from PCR study of five other hysterectomy and salpingo-oophorectomy specimens (control cases). The criteria used for selection of the control cases were informed consent of the patients for research at the time of surgery, absence of neoplasms, absence of any anatomic lesion caused by HPV in cervix, and external genitalia. All selected cases were squamous cervical carcinomas. PCR analysis revealed HPV DNA in all cases of cervical carcinoma. The HPV DNA was detected as weak positivity on PCR analysis in other organs of the genital system. However, the distribution of HPV DNA varied in the various cases and in the different tracts of the same hysterectomy and salpingo-oophorectomy specimen. We believe that the HPV DNA, detected as a weakly positive signal, in the upper genital tract of patients who have a cervical squamous carcinoma could be a reflection of a latent HPV infection, as well as a sign of the existence of micrometastases containing HPV DNA, which cannot be detected by conventional histologic techniques.

Detection of human papillomavirus in organs of upper genital tract in women with cervical cancer

In this study, we evaluated the presence of human papillomavirus (HPV) DNA in organs of the female upper genital tract, using nine hysterectomy and salpingo-oophorectomy specimens affected by HPV-positive invasive cervical carcinomas, to establish if cervical HPV infection can spread to upper tracts of the female genital system. HPV DNA was evaluated by polymerase chain reaction (PCR) in all cervical carcinomas as well as in all tracts of the genital system. Then, these data were compared with the results obtained from PCR study of five other hysterectomy and salpingo-oophorectomy specimens (control cases). The criteria used for selection of the control cases were informed consent of the patients for research at the time of surgery, absence of neoplasms, absence of any anatomic lesion caused by HPV in cervix, and external genitalia. All selected cases were squamous cervical carcinomas. PCR analysis revealed HPV DNA in all cases of cervical carcinoma. The HPV DNA was detected as weak positivity on PCR analysis in other organs of the genital system. However, the distribution of HPV DNA varied in the various cases and in the different tracts of the same hysterectomy and salpingo-oophorectomy specimen. We believe that the HPV DNA, detected as a weakly positive signal, in the upper genital tract of patients who have a cervical squamous carcinoma could be a reflection of a latent HPV infection, as well as a sign of the existence of micrometastases containing HPV DNA, which cannot be detected by conventional histologic techniques.

Serological Detection of Human Papillomavirus Type 16 Infection in Human Immunodeficiency Virus (HIV)-Positive and High-Risk HIV-Negative Women

Serial measurement of antibodies has not been used to provide evidence of active viral replication of human papillomavirus (HPV). Serum specimens from sequential study visits contributed by 642 human immunodeficiency virus (HIV)-positive and 116 HIV-negative participants enrolled in the Women's Interagency HIV Study were used to detect significant rises in HPV type 16 (HPV-16) antibody levels. Factors associated with a significant rise were identified using multivariable logistic regression models with generalized estimating equations. Among HIV-positive women, 8.3% of 1,997 pairs showed antibody rises, compared to 6.1% of 361 pairs among HIV-negative women (P = 0.191). For HIV-positive women, rises were associated with current (odds ratio [OR], 23.4; P < 0.001) or past (OR, 8.9; P < 0.001) HPV-16 infection relative to never being HPV-16 infected and with CD4+ cell counts (OR per 100-cell increase, 0.8; P < 0.001) but not with sexual behavior. For HIV-negative women, rises were associated with past (OR, 10.9; P = 0.033) HPV-16 infection relative to no HPV-16, current cigarette smoking (OR, 5.0; P = 0.029) relative to no smoking history, and having 6 to 10 lifetime sexual partners compared to 0 to 5 partners (OR, 9.9; P = 0.036). Serial measurement of HPV-16 serum antibodies is a useful tool for identifying active HPV-16 viral replication. Rises among HIV-positive women may more often result from reactivation of a latent HPV infection in the context of HIV-induced immunosuppression, while rises among HIV-negative women may more often result from reinfection with HPV.

Clinical Trial of Photodynamic Therapy With Meso-Tetra (Hydroxyphenyl) Chlorin for Respiratory Papillomatosis

To determine the efficacy of photodynamic therapy (PDT) with meso-tetra (hydroxyphenyl) chlorin (m-THPC) photosensitizer for recurrent respiratory papillomatosis. Parallel-arm, randomized trial of patients requiring surgery at least 3 times yearly with single PDT 6 or 18 months after enrollment and 12-month follow-up. Disease extent was scored and papillomas were removed during direct endoscopy every 3 months after enrollment. Tertiary medical centers. Of 23 patients aged 4 to 60 years enrolled in the study, 15 patients, plus 2 in the late group without PDT owing to airway risk, completed the study. Six patients withdrew voluntarily after PDT. Intravenous administration of m-THPC 6 days before direct endoscopic PDT with 80 to 100 J of light for adults and 60 to 80 J for children. Difference in severity scores between the early and late groups and between pre- and post-PDT scores for all patients. Secondary measures were the associations between baseline characteristics and response and changes in immune response and the prevalence of latent viral DNA. There were significant differences between groups, with marked improvement in laryngeal disease across time after PDT (P = .006). Five of 15 patients were in remission 12 to 15 months after treatment, but there was recurrence of disease after 3 to 5 years. Tracheal disease was not responsive to PDT. No change occurred in the prevalence of latent human papillomavirus DNA. The immune response to virus improved with clinical response. Use of m-THPC PDT reduces the severity of laryngeal papillomas, possibly through an improved immune response. Failure to maintain remission with time suggests that this is not an optimal treatment.

Effets de l’imiquimod sur l’infection périanale latente à papillomavirus humain chez des malades infectés par le virus de l’immunodéficience humaine

High risk human papillomaviruses (HPV) have emerged as risk factors for anal carcinoma particularly in HIV-infected patients who demonstrate a high rate of anal HPV infection. Considering the relationship between the presence of anal infection and the development of neoplastic lesions, we wished to assess the capacity of imiquimod to eradicate latent HPV infection in HIV-infected patients. We conducted a prospective, randomized, double-blind and vehicle controlled study. Two consecutive anal swabs were taken at 2 month intervals and only patients with two consecutive tests positive for the detection of HPV-DNA (Hybrid Capture II) were included. Patients with persistent latent HPV infection were divided into 2 groups who applied imiquimod versus vehicle during 6 weeks. HPV-DNA presence was then investigated 2 and 4 months following the onset of treatment. Among the 80 HIV-infected patients, 26 (32.5 p. 100) had 2 positive consecutive assays, and 19 patients were included in the study. After randomization, 9 patients received imiquimod and 10 vehicle. There was no significant difference between treatment groups according to the following criteria: gender, route of HIV transmission, CDC stage, prior medical history of sexually transmitted diseases or anogenital warts. 33.3 p. 100 (3/9) of patients treated with imiquimod were negative at M2, whereas 100 p. 100 (10/10) vehicle treated-patients remained positive (p=0.08). Similar results were observed at the M4 visit. Our study confirmed the increased prevalence of latent HPV-DNA infection in HIV-infected patients. In spite of the low number of treated patients, we did not observe a statistically significant decrease in HPV-DNA in anal swabs from imiquimod-treated patients as compared to placebo-treated patients.

Latent Human Papillomavirus infection is comparable in the larynx and trachea.

Recurrent respiratory papillomas are benign airway tumors caused by Human Papillomaviruses (HPVs) types 6 and 11. The disease is characterized by multiple recurrences of papillomas following surgical removal, caused by activation of latent HPV DNA. Most patients have laryngeal disease, while only a small subset has tracheal involvement. We have asked whether the lower frequency of tracheal papillomas was due to reduced prevalence of latent/subclinical tracheal HPV infection or reduced likelihood of activation to clinically apparent disease. A total of 121 biopsies of clinically normal laryngeal and tracheal tissues from 61 patients with laryngeal papillomas were analyzed for HPV DNA by polymerase chain reaction, confirmed by Southern blot hybridization. Patients were followed for 3-18 years (mean = 5.5 +/- 4.4), with only one developing subsequent tracheal disease. There was no significant difference in prevalence of latent HPV DNA between larynx and trachea, analyzing either those patients with a single biopsy or those with more than one biopsy of larynx, trachea, or both. There was also no significant difference between tracheal latency with HPV 6 and HPV 11. We conclude that HPV infects tracheal mucosa and is maintained as a latent infection in the trachea as efficiently as in the larynx. Therefore, we propose that the low frequency of tracheal disease reflects a lower frequency of HPV activation, and postulate that cellular factors that differ between the stratified squamous epithelium of the larynx and the ciliated pseudo-stratified columnar epithelium of the trachea contribute to this difference.

Human papillomaviruses

Human papillomaviruses (HPV) infect exclusively the basal cells of the skin and of mucosal epithelia adjacent to the skin such as the mouth, the upper respiratory tract, the lower genital tract and the anal canal. HPV does not lead to a viremia. Basically there are three different types of HPV infection: Clinically visible lesions, subclinical HPV infections and latent HPV infections. Distinct HPV types induce morphologically and prognostically different clinical pictures. The most common HPV associated benign tumor of the skin is the common wart. Infections of the urogenitoanal tract with specific HPV-types are recognised as the most frequent sexually transmitted viral infections. So-called "high-risk" HPV-types (HPV16, 18 and others) are regarded by the world health organisation as important risk-factors for the development of genital cancer (mainly cervical cancer), anal cancer and upper respiratory tract cancer in both genders. Antiviral substances with a specific anti-HPV effect are so far unknown. Conventional therapies of benign skin warts and of mucosal warts are mainly nonspecific. They comprise tissue-destroying therapies such as electrocautery, cryotherapy and laser. In addition cytotoxic substances such as podophyllotoxin and systemic therapy with retinoids are in use. Systemically and topically administered immunotherapies represent a new approach for treatment. Both interferons and particularly the recently developed imiquimod, an interferon-alpha and cytokine-inductor lead to better results and are better tolerated then conventional therapies. HPV-specific vaccines have been developed in the last 5 years and will be used in future for prevention and treatment of benign and malignant HPV-associated tumors of the genitoanal tract in both sexes.

Genotyping of 22 human papillomavirus types by DNA chip in Korean women: Comparison with cytologic diagnosis

Objective: More sensitive and reliable methods than individual testing (such as polymerase chain reaction, restriction fragment length polymorphism, and Southern blot) should be developed as screening tools for the detection of latent human papillomavirus. Today, the new Bethesda system recommends human papillomavirus testing as an adjuvant to the conventional Papanicolaou smear for more comprehensive identification of women at certain risk of cervical neoplasia. We performed human papillomavirus genotyping with the newly designed human papillomavirus DNA chip, which is based on polymerase chain reaction for high-throughput screening power, and compared the results with the results of a Papanicolaou smear according to the new Bethesda system. Study Design: Polymerase chain reaction amplifications of the human papillomavirus L1 region from biologic samples were hybridized to silanized glass slides by a microarrayer, which comprised 22 specific oligonucleotide probes to their genotypes, consisting of 15 high-risk and 7 low-risk types. Two cervical cancer cell lines and 20 plasmids that contained each type of the human papillomavirus whole genome were used for the evaluation of this method; in all cases, the cancer cell lines and plasmids showed clear positive signals on their corresponding positions. A comparative study that used 685 cervicovaginal swabs was performed by human papillomavirus DNA chip microarray together with Papanicolaou diagnosis. Results: Human papillomavirus was identified as positive in 31.9% of the 414 control samples and in 78.6% of the 271 neoplastic lesions. The major prevailing human papillomavirus genotypes were human papillomavirus types 16, 58, and 18, in descending order of incidence (average overall, 78.8%). Almost all of the remaining cases were comprised of human papillomavirus types 39, 52, 56, and 51. The frequency of multiple infection of human papillomavirus was highest in low-grade squamous intraepithelial lesion but was lowest in squamous cell carcinoma. All cases that exhibited infection of single human papillomavirus type 58 were squamous cell carcinoma. Conclusion: Human papillomavirus types 16, 18, and 58 were confirmed to be major causative factors for cervical carcinogenesis. Low-grade squamous intraepithelial lesion is a heterogeneous entity that is composed of different human papillomavirus subtypes and prevails in younger women (<40 years old). The human papillomavirus chip has potential use as a high-throughput screening test. (Am J Obstet Gynecol 2003;188:56-62.)

Treatment of genital warts - what's the evidence?

Genital warts are usually asymptomatic, and rarely cause discomfort. Once the patient is aware of them the main symptom is their cosmetic appearance and resultant psychological consequences. The ideal treatment outcome would be complete viral eradication, but this is not possible. Treatments focus on the removal of exophytic warts, leaving the surrounding subclinical and latent human papillomavirus (HPV) infection as areas of possible transmission and recurrence. Effective treatment does reduce HPV viral load, so the infection is reduced if not completely eradicated. Treatment is often painful, inconvenient, and may produce poor clearance rates and frequent recurrences. The treatment chosen should be no worse or more dangerous than the disease itself, and should be tailored to the patients' disease and needs as well as to the available resources. Genital warts are highly infectious and sexual partners may well already be infected when a patient presents for treatment. There are no published studies showing that condom use reduces transmission of HPV from people with genital warts. However, if the sexual partner is uninfected; using a condom may protect against HPV lesions and genital warts. Condom use should be encouraged in new relationships.

Epidemiology of HPV infection among Mexican women with normal cervical cytology.

Cervical cancer is caused by human papillomavirus (HPV) and is the most common cancer among Mexican women, but no population-based studies have reported the prevalence and determinants of HPV infection in Mexico. A population-based study was carried out between 1996 and 1999, based on an age-stratified random sample of 1,340 women with normal cytologic diagnoses from 33 municipalities of Morelos State, Mexico. The prevalence of cervical HPV DNA was determined by reverse line blot strip assay to detect 17 cancer-associated and 10 non-cancer-associated HPV types. Two peaks of HPV DNA prevalence were observed. A first peak of 16.7% was observed in the age group under 25 years. HPV DNA prevalence declined to 3.7% in the age group 35-44 years, then increased progressively to 23% among women 65 years and older. Cancer-associated HPV types were the most common in all age groups; non-cancer-associated HPV types were rare in the young and became more common linearly with age. Twenty-four types of HPV were detected; HPV 16, HPV 53, HPV 31 and HPV 18 were the most common, but none was present in more than 1.7% of subjects. The main determinant of infection with both cancer-associated and non-cancer-associated HPV types was the number of sexual partners in all age groups. Less-educated women were at an increased risk of infection with cancer-associated but not with non-cancer-associated HPV types; low socioeconomic status was associated with detection of non-cancer-associated HPV types. Among young women an increasing number of pregnancies was associated with lower HPV detection and among older women low socioeconomic status was related to increased HPV detection, particularly for the age group 35-54 years. Among women with cancer-associated HPV types, there was a higher intensity of polymerase chain reaction signal in younger than in older age groups (p < 0.001). We present additional evidence for the sexually transmitted nature of HPV infection, regardless of age group and HPV type. We confirm previous findings of a second peak of high-risk HPV infections in postmenopausal women, in this case with a clear predominance of cancer-associated HPV types. In populations with this pattern, which can be related to reactivation of latent HPV infections or high previous exposure in older women, screening with HPV testing can have a reduced specificity among older women if proper cut-off points for HPV positivity are not used. Longitudinal studies of immune responses to HPV infection in different age groups are warranted.

Clinical and Viral Clearance of Human Papillomavirus (HPV)-Associated Genital Lesions by Nd:YAG-Laser Treatment

Summary Objectives: HPV-associated genital lesions are treated with various medications and by surgery. The effectiveness of the individual methods in eliminating genital warts can vary substantially and depends on numerous factors. Up to now, no method of treatment has been able to prevent reliably the manifestation of recurrences of HPV lesions. The present study will evaluate the clinical and viral clearance of genital warts by Nd:YAG laser treatment. Methods: An average of four years after Nd:YAG laser treatment of clinical and subclinical HPV lesions of the external genitals, follow-up examinations were carried out in 103 men. After thorough investigation with acetic acid testing and lens magnification, biopsies were taken both from clinical and subclinical HPV recurrences as well as from laser scars and normal epithelia at a distance of 1 cm from these. These skin specimens were investigated by PCR. HPV types were identified by RFLP analysis of the PCR products and subsequent hybridization with a generic probe. Results: Follow-up investigations revealed that genital warts were again present in 27 men, and there were subclinical HPV lesions in seven men. In one case, a carcinoma of the penis was diagnosed. Apart from this carcinoma, all clinical and subclinical recurrences showed positive results in laboratory testing for HPV. None of the recurrences were in the area of the laser scar. The HPV analyses showed latent HPV infections in 16 patients. Only 56 out of 103 men could be categorized as cleared with regard to HPV infection after Nd:YAG laser treatment both clinically and in terms of laboratory tests. In all, 27 different HPV genotypes of the external genitals were demonstrated. Conclusions: A mere clinical appraisal of the effectiveness of a method of treating HPV is relatively unreliable with regard to the rates of recurrence, since recurrences can develop once more after a long time in persistent latent HPV infections of the genitals. Our long-term laboratory test to follow up the laser treated areas that also included normal genital skin revealed a very much larger area of HPV infections of the genitals than was inferred from clinical HPV recurrences. Since recurrences were never localized in laser scars, an excellent rate of local clearance of genital warts by the Nd:YAG laser treatment resulted in purely clinical terms. However, complete viral clearance was not achieved. Nor was an immune response induced that could have prevented development of a recurrence deriving from untreated latent HPV infected genital skin.

Treatment of warts

ABSTRACT: Warts are caused by human papilloma viruses (HPV) and more than 80 types of HPV have been described. Although some HPV types in the anogenital area can lead to dysplasia and cancer, most HPV infections cause histologically benign warts. Clinically, warts produce much morbidity, mainly due to their resistance to most standard therapies. Although the choice of therapy depends partly on the location of the warts, i.e., anogenital vs. non-anogenital, most treatments in the past have been anti-wart but not antiviral. Therefore, removal of the wart was often followed by a recurrence in a few weeks due to sub-clinical or latent HPV infections surrounding the wart. Such non-antiviral therapies included a variety of acids, podophyllin, podophyllotoxin, chemotherapeutic agents, retinoids, topical sensitizers, a spectrum of surgical techniques, and cryotherapy. Two drugs approved for anogenital warts have antiviral and immunomodulatory activity, interferon and imiquimod, although imiquimod is much more convenient to use. While neither of these antiviral agents is approved for non-anogenital warts, they do appear to have efficacy in these warts when used as adjunctive therapy. Experimental therapies for warts are currently under study and include topical cidofovir and both prophylactic and therapeutic HPV vaccines.