OBJECTIVES:Obese women are at increased risk of cervical cancer, partly due to missed detection of cervical precancers during routine cervical cancer screening. We administered a clinician survey to better understand specific challenges and identify potential solutions to performing cervical cancer screening and management in obese women.MATERIALS AND METHODS:We administered a web-based survey to 2,319 members of the American Society of Colposcopy and Cervical Pathology including questions related to challenges associated with cervical sampling and visualization in obese compared with normal weight women and potential strategies for improvement. We summarized providers' responses using descriptive statistics and used Fisher exact tests to evaluate associations between provider characteristics and challenges with cervical sampling, visualization, and biopsy.RESULTS:Of the 240 providers that completed the survey, 89% and 93% reported that cervical sampling and visualization are more challenging in obese women, respectively, whereas 80% reported that taking a biopsy was more challenging. Commonly reported barriers included vaginal prolapse, difficulty visualizing and accessing the cervix, and lack of long enough sampling devices and large enough speculums. Frequently used techniques to improve sampling and visualization included use of a condom or examination glove finger to sheath a speculum and using a tenaculum. Most providers identified training for cervical sampling and colposcopy in obese women as a learning gap, and only 8% reported receiving such training.CONCLUSIONS:Cervical cancer screening and management are more challenging in obese compared with normal weight women. Major barriers to cervical sampling and visualization included lack of adequately sized equipment and lack of education and training.

Ingrown toenails account for approximately 20% of foot problems in primary care. The great toe is most often affected. Ingrown toenails occur most commonly in young men, and nail care habits and footwear are most often contributory factors. No consensus has been reached for the best treatment approach, but ingrown nails may be nonsurgically or surgically treated. Nonsurgical treatments are typically used for mild to moderate ingrown nails, whereas surgical approaches are used in moderate and severe cases. Simple nonsurgical palliative measures include correcting inappropriate footwear, managing hyperhidrosis and onychomycosis, soaking the affected toe followed by applying a mid- to high-potency topical steroid, and placing wisps of cotton or dental floss under the ingrown lateral nail edge. Application of a gutter splint to the ingrown nail edge to separate it from the lateral fold provides immediate pain relief. A cotton nail cast made from cotton and cyanoacrylate adhesive, taping the lateral nail fold, or orthonyxia may also alleviate mild to moderate ingrown toenail. Surgical approaches seek to remove the interaction between the nail plate and the nail fold to eliminate local trauma and inflammatory reaction. These approaches are superior to nonsurgical ones for preventing recurrence. The most common surgical approach is partial avulsion of the lateral edge of the nail plate. Matrixectomy further prevents recurrence and can be performed through surgical, chemical, or electrosurgical means.

Nail lesions can be related to a number of disease states. These may be intrinsic to the nail, caused by infection, or reflect systemic disease. Careful history and examination often is necessary for accurate diagnosis. Anatomy and gross changes of the nail are reviewed. The diagnosis and treatment of disease process such as psoriasis, lichen planus, paronychia, onychomycosis, myxoid cysts, and pincer nails are reviewed.

Objectives: The American Society for Colposcopy and Cervical Pathology Colposcopy Standards address the role of and approach to colposcopy and biopsy for cervical cancer prevention in the United States. Working Group 1 was tasked with defining the role of colposcopy, describing benefits and potential harms, and developing an official terminology.Methods: A systematic literature review was performed. A national survey of American Society for Colposcopy and Cervical Pathology members provided input on current terminology use. The 2011 International Federation for Cervical Pathology and Colposcopy terminology was used as a template and modified to fit colposcopic practice in the United States. For areaswithout data, expert consensus guided the recommendation. Draft recommendations were posted online for public comment and presented at an open session of the 2017 International Federation for Cervical Pathology and Colposcopy World Congress for further comment. All comments were considered for the final version.Results: Colposcopy is used in the evaluation of abnormal or inconclusive cervical cancer screening tests. Colposcopy aids the identification of cervical precancers that can be treated, and it allows for conservative management of abnormalities unlikely to progress. The potential harms of colposcopy include pain, psychological distress, and adverse effects of the procedure. A comprehensive colposcopy examination should include documentation of cervix visibility, squamocolumnar junction visibility, presence of acetowhitening, presence of a lesion(s), lesion (s) visibility, size and location of lesions, vascular changes, other features of lesion(s), and colposcopic impression. Minimum criteria for reporting include squamocolumnar junction visibility, presence of acetowhitening, presence of a lesion(s), and colposcopic impression.Conclusions: A recommended terminology for use in US colposcopic practice was developed, with comprehensive and minimal criteria for reporting.

ObjectiveVaginal cancer is an uncommon cancer of the lower genital tract, and standardized screening is not recommended. Risk factors for vaginal cancer include a history of other lower genital tract neoplasia or cancer, smoking, immunosuppression, and exposure to diethylstilbestrol in utero. Although cervical cancer screening after total hysterectomy for benign disease is not recommended, many women inappropriately undergo vaginal cytology and/or human papillomavirus (HPV) tests, and clinicians are faced with managing their abnormal results. Our objectives were to review the literature on vaginal cytology and high-risk HPV (hrHPV) testing and to develop guidance for the management of abnormal vaginal screening tests. Materials and MethodsAn electronic search of the PubMed database through 2015 was performed. Articles describing vaginal cytology or vaginal hrHPV testing were reviewed, and diagnostic accuracy of these tests when available was noted. ResultsThe available literature was too limited to develop evidence-based recommendations for managing abnormal vaginal cytology and hrHPV screening tests. However, the data did show that (1) the risk of vaginal cancer in women after hysterectomy is extremely low, justifying the recommendation against routine screening, and (2) in women for whom surveillance is recommended, e.g., women posttreatment for cervical precancer or cancer, hrHPV testing may be useful in identification of vaginal cancer precursors. ConclusionsVaginal cancer is rare, and asymptomatic low-risk women should not be screened. An algorithm based on expert opinion is proposed for managing women with abnormal vaginal test results.

ObjectiveVaginal cancer is an uncommon cancer of the lower genital tract, and standardized screening is not recommended. Risk factors for vaginal cancer include a history of other lower genital tract neoplasia or cancer, smoking, immunosuppression, and exposure to diethylstilbestrol in utero. Although cervical cancer screening after total hysterectomy for benign disease is not recommended, many women inappropriately undergo vaginal cytology and/or human papillomavirus (HPV) tests, and clinicians are faced with managing their abnormal results. Our objectives were to review the literature on vaginal cytology and high-risk HPV (hrHPV) testing and to develop guidance for the management of abnormal vaginal screening tests.Materials and MethodsAn electronic search of the PubMed database through 2015 was performed. Articles describing vaginal cytology or vaginal hrHPV testing were reviewed, and diagnostic accuracy of these tests when available was noted.ResultsThe available literature was too limited to develop evidence-based recommendations for managing abnormal vaginal cytology and hrHPV screening tests. However, the data did show that (1) the risk of vaginal cancer in women after hysterectomy is extremely low, justifying the recommendation against routine screening, and (2) in women for whom surveillance is recommended, e.g., women posttreatment for cervical precancer or cancer, hrHPV testing may be useful in identification of vaginal cancer precursors.ConclusionsVaginal cancer is rare, and asymptomatic low-risk women should not be screened. An algorithm based on expert opinion is proposed for managing women with abnormal vaginal test results.

Vaginal cancer is an uncommon cancer of the lower genital tract, and standardized screening is not recommended. Risk factors for vaginal cancer include a history of other lower genital tract neoplasia or cancer, smoking, immunosuppression, and exposure to diethylstilbestrol in utero. Although cervical cancer screening after total hysterectomy for benign disease is not recommended, many women inappropriately undergo vaginal cytology and/or human papillomavirus (HPV) tests, and clinicians are faced with managing their abnormal results. Our objectives were to review the literature on vaginal cytology and high-risk HPV (hrHPV) testing and to develop guidance for the management of abnormal vaginal screening tests.An electronic search of the PubMed database through 2015 was performed. Articles describing vaginal cytology or vaginal hrHPV testing were reviewed, and diagnostic accuracy of these tests when available was noted.The available literature was too limited to develop evidence-based recommendations for managing abnormal vaginal cytology and hrHPV screening tests. However, the data did show that (1) the risk of vaginal cancer in women after hysterectomy is extremely low, justifying the recommendation against routine screening, and (2) in women for whom surveillance is recommended, e.g., women posttreatment for cervical precancer or cancer, hrHPV testing may be useful in identification of vaginal cancer precursors.Vaginal cancer is rare, and asymptomatic low-risk women should not be screened. An algorithm based on expert opinion is proposed for managing women with abnormal vaginal test results.

INTRODUCTION:Blood pressure (BP) elevation in medical office settings in patients who are normotensive in nonmedical settings is an effect known as 'white coat hypertension'. This phenomenon is thought to be due to situational anxiety caused by the experience of visiting a doctor and the anxiety-inducing nature of the medical office. Our study was designed to determine if carefully selected photographic art could counter the anxiety that causes white coat hypertension and lead to lower BP recordings in some patients.METHODS:117 adults, non-pregnant patients from the Louisiana State University Health Sciences Center Family Medicine Resident Clinic participated in this study. After the triage nurse measured the BP, the patients were randomly placed in either an exam room with standard medical posters (control room) or in an exam room with photographic art (photo room). The BP was measured in the exam room. After the medical visit, the patients switched rooms and the BP was measured a third time. The patients were asked to fill out a questionnaire to identify room preference.RESULTS:On average, the BP obtained in the control rooms was higher than that obtained in the photo rooms. There was a statistically significant difference between the mean arterial pressure, systolic BP and diastolic BP between the control room and the photo room.CONCLUSIONS:Landscape photographic art may have the beneficial effect of reducing BP in medical office examination rooms.

Being able to promptly recognize and diagnose oral lesions is critical to heading off several potentially serious conditions. This article and photo guide can help.

Human papillomavirus (HPV) is the most common viral cause of cancer, and is responsible for 5% of cancers worldwide. Following demonstration of the causative link between HPV and cervical cancer, HPV has been shown to be associated with several anogenital malignancies and with oral pharyngeal cancers. HPV-related anal and oral pharyngeal disease is rising in incidence and includes anal warts and neoplasia, recurrent respiratory papillomatosis, and oral pharyngeal neoplasia. This article presents an overview of the epidemiology, clinical manifestations, diagnosis, and treatment of nongenital HPV-related disease.

The patient was initially told she had cellulitis and sent home with a combination antibiotic. Three weeks later, she returned with necrotic lesions.

In theory, recognition that a pandemic infection is responsible for more than half a million cancer cases each year would attract huge media attention, and infection control would become the subject of preventative efforts from all global health agencies. Media attention would likely be particularly acute if the majority of deaths was among women rearing families in the developing world and if the disease were sexually transmitted. A vaccine capable of preventing the disease would be diligently pursued and, once available, promptly distributed for the health and welfare of humankind. Human papillomavirus (HPV) infection fits this scenario; however, HPV has yet to make an impact on either the media or public thinking as outlined in the previous paragraph, even though the link between HPV infection and cervical cancer has been recognized for more than 20 years. It is possible that the delay between acquisition of HPV infection and death, on average 20 years, or the asymptomatic nature of acute infection, greatly diminishes the immediacy of the public impact of this epidemic. Although apparently safe vaccines capable of preventing >90% of HPV infections are in the offing, focus on prevention of HPV associated deaths is being diverted by debates about the morality of vaccination against a sexually transmitted infection and its hypothesized impact on human sexual behavior. A roundtable discussion was held in Vancouver, British Columbia to consider and develop a consensus statement among informed clinicians about HPV infection, the role of HPV in cervical cancer, the role of HPV in other anogenital malignancies, the role of HPV in genital warts and the prospects for control of the global HPV pandemic through vaccination. The consensus statements outlined within have been agreed upon and represent the informed opinions of this expert working group. CONSENSUS 1: GENITAL HPV-ASSOCIATED DISEASE IS A MAJOR HEALTH CARE BURDEN HPV infection is the cause of genital warts and most preinvasive and invasive cancers of the lower anogenital tract. Clinically or histologically recognized genital warts, abnormal cervical cytology and preinvasive or invasive cancer are major causes of physical and psychologic morbidity and of treatment-related cost. The Causal Relationship Between HPV and HPV-Associated Diseases Papillomaviruses are small, nonenveloped viruses that infect cutaneous and mucosal epithelial tissues. More than 100 types of HPV have been identified, of which more than 40 infect the genital mucosa (Fig. 1). 1 The life cycle of HPV is dependent on active cellular replication and subsequent cellular division. Because the uppermost layers of the squamous epithelium have undergone terminal differentiation and are no longer dividing, HPV requires access to the undifferentiated basal layer of the epithelium to initiate a productive infection cycle. Current hypotheses suggest that HPV accesses the underlying basal layer through naturally thin epithelial layers, such as those found in the transformation zones of the cervix or anus, or through microabrasions in the epithelium produced during sexual activity.2 Once infection has been established, the virus uses host cell machinery to replicate viral genetic material and express viral proteins. Because viral replication is dependent on continued cellular division, the virus has evolved to express proteins that inhibit cellular differentiation and stimulate continued cellular proliferation (Fig. 2) (for an in-depth review of HPV pathology, see Reference 3). Therefore, unrestricted cell growth is the hallmark of HPV infection, and many HPV-associated clinical manifestations can be explained by these molecular mechanisms.FIGURE 1.: Phylogenetic tree containing the sequences of 118 papillomavirus types.1FIGURE 2.: Natural history of HPV infection of mucosal epithelial layers. A, HPV infects the basal layer of the epithelium. B, The virus uses host cell machinery to replicate viral DNA and express virally encoded proteins. C, Viral particles are formed and released.3High Risk HPV Infections Genital HPV types have been separated into high and low risk groups depending on the observed risk of malignant progression (Table 1). The distinction between high and low risk HPV types has been made primarily because clinical diseases caused by infection with low risk HPV types are usually clinically benign and rarely progress to neoplasia. High risk HPV types are responsible for most high grade, precancerous lesions and >99.7% of cervical cancers.4 HPV 16 alone is the cause of more than half of all invasive cancers. By considering the number of HPV 16, HPV 18 and HPV 16/18 coinfections, epidemiologists have shown that HPV 16 and 18 are cumulatively responsible for >70% of all cervical cancers and the majority of precancerous intraepithelial neoplasias commonly detected during routine cervical cancer cytology screens.5 The evidence for causality of HPV in cervical cancer is so strong that the International Agency for Research on Cancer (IARC), part of the World Health Organization (WHO), and the National Toxicology Program have officially acknowledged high risk HPV as a known human carcinogen.6,7 The IARC has recognized HPV as a human carcinogen since 1995 and recently revisited and confirmed the issue in 2005.8TABLE 1: Epidemiologic Classification of Genital HPV Types Associated With Clinical Disease4Before the advent of cervical cancer screening programs, little was known about the natural course of cervical cancer disease progression. Today, however, the natural history of cervical cancer development is better understood, in large part because of cervical cancer screenings and several recent large longitudinal epidemiologic studies. Although cervical carcinogenesis is not discussed here, some HPV infections are thought to cause low grade lesions, which may progress to high grade lesions and then may lead to carcinoma in situ and cervical cancer (for an in-depth review of the natural history of cervical cancer, see Reference 2). Mortality associated with cervical cancer has declined >70% since the inception of the Papanicolaou (Pap) test and implementation of routine cervical cancer screening in most Western countries.9 Today an estimated 50 million Pap tests are performed annually in the United States alone. As a result, each year 2–3 million women are diagnosed with atypical squamous cells (ASC), 1.25 million with low grade squamous intraepithelial lesions (LSIL), 300,000 with high grade squamous intraepithelial lesions (HSIL) and >10,000 with cervical cancer.10 Despite widespread screening, an estimated 4000 women in the United States die of cervical cancer annually. The economic burden associated with HPV infection is substantial. Including the costs of cervical cancer screening and treatment of preinvasive and invasive cancerous lesions, total cost estimates for the United States range from 1 to 6 billion dollars annually, making HPV the second most costly sexually transmitted infection (STI), second only to human immunodeficiency virus (HIV).11,12 Costs associated with HPV infection include cervical cytology, management of low and high grade lesions, treatment of cervical cancer and expenditures related to follow-up of false positive Pap test results (Fig. 3). Although the settings and health care costs associated with treatment can vary, one study has reported that routine Pap tests cost ∼$60, and management of low and high grade lesions costs $1026 and $3235, respectively.13 If the indirect costs (eg, lost work time and wages) associated with cervical cancer screening and follow-up of abnormal Pap test results were included, these estimates would increase substantially.FIGURE 3.: HPV-associated costs in the United States.13It is well-appreciated that HPV is a necessary cause of cervical cancers, and evidence supporting a role for high risk HPV types in the etiology of other malignant genital and mucosal lesions is accumulating. HPV has been linked to the etiology of a proportion of anal, penile, scrotal, vulvar, vaginal and some head and neck cancers (eg, tonsillar, conjunctival).2,14 The epidemiology and costs associated with these cancers are not well-documented; however, determining the role that HPV plays in the development of each of these cancers is an area of ongoing research. Recently published epidemiologic studies have identified a causal relationship between HPV infection and anal cancer.14 The incidence of anal cancer is increasing in the general population and rates are particularly high in men who have sex with men and patients who are immunocompromised, such as HIV-infected individuals.15 The role of HPV in the etiology of anal intraepithelial neoplasia and anal cancer is generally not well-appreciated by health care professionals, and there is sufficient scientific evidence available to warrant escalating awareness of HPV and anal cancer.14,16 HPV-associated anal disease will be discussed in detail later in this document. Low Risk HPV Infections Infection with low risk HPV types is also associated with clinical diseases that involve epithelial hyperproliferation. In addition to causing ∼25% of LSIL, infection with low risk HPV is responsible for all cases of recurrent respiratory papillomatosis and nearly all anogenital warts. Although condylomata acuminata, or genital warts, are clinically benign, they are a significant cause of morbidity in affected men and women. HPV types 6 and 11, the 2 most common disease-causing low risk HPV types, are responsible for 97% of genital wart manifestations.17 Current estimates suggest that >1% of the sexually active population has genital warts,18 and the Centers for Disease Control and Prevention estimate that genital warts prompt ∼240,000 initial visits to physicians’ offices, in addition to nearly 5% of all visits to sexually transmitted disease clinics.19 Treatment modalities are frequently painful, involving excision or desiccation of the lesion and usually require multiple treatments to be effective. Indeed up to 75% of treated genital warts recur within 6 months of treatment.20 Costs associated with treatment are highly variable. One study has shown that the average costs for complete clearance of the lesion are as follows: surgical excision is lowest at $285; cryotherapy costs $951; and interferon treatment is most expensive at $6665 (Fig. 4). 21FIGURE 4.: Average direct medical costs associated with treatment of genital warts in the United States. * Includes costs of physician visits (initial visits and subsequent treatment visits) and costs of medications/procedures. LEEP indicates loop electrosurgical excision procedure; TCA, trichloroacetic acid.21Recurrent respiratory papillomatosis (RRP) is a rare but serious consequence of HPV infection in children. RRP is caused by benign proliferative growths induced by HPV 6 or 11 infection of the laryngeal mucosa.22 Children with RRP are infected during childbirth when HPV-infected mothers pass the infection to their infants. Up to 3000 cases of juvenile RRP are diagnosed and treated annually and require up to 4 surgical treatments per year to remove lesions.23 Moreover up to 3% of children with RRP will die of the disease.23 Psychologic Burden of HPV Infection Intangible costs associated with HPV infection are harder to measure. It is well-established that HPV is a significant source of psychologic distress among patients who develop or are diagnosed with genital warts, have an abnormal Pap test result or are treated for precancerous lesions or invasive cancer. It has been suggested that many of these concerns and negative feelings are brought on by perceptions of promiscuity associated with acquisition of an STI.24 After learning that they have contracted HPV, some patients develop persistent psychosocial issues that interfere with present and future relationships.25 Patients diagnosed with genital warts report feeling very angry or depressed. Others report feeling disgusted and blame themselves.26 Following diagnosis with precancerous lesions, women have reported difficulties coping with work and caring for their families, all of which negatively affect overall quality of life.24 Alternatively, after treatment of cervical precancers and cancers, patients may develop psychosexual concerns that lead to sexual dysfunction or issues with fertility and sexuality.27 Thus any reductions in the incidence of HPV-associated disease would be expected to alleviate large proportions of both psychologic and economic health care burden. CONSENSUS 2: INCIDENCE OF GENITAL HPV INFECTIONS AND HPV-ASSOCIATED CLINICAL DISEASE IS GREATEST IN MEN AND WOMEN WHO HAVE RECENTLY BECOME SEXUALLY ACTIVE Most sexually active men and women will acquire genital HPV infection The risk of infection increases substantially with each new partner Condom use may not be fully protective Prevalence of and Acquisition of HPV Among Adolescent and Young Adult Populations HPV is the most common STI in the world. In the United States, an estimated 20 million people are currently infected with this virus, with incidence rates approaching 6.2 million new infections each year.28,29 At least 75% of the female population has been or will become infected throughout their lifetimes (Fig. 5). 18,30 Thus the majority of sexually active individuals, from adolescents to adults, are at risk for acquiring HPV. Although men and women 15–24 years of age represent only 25% of the sexually active population 15–44 years of age, nearly half of all STIs are diagnosed in this age group (Fig. 6). 29 The prevalence of active HPV infections in adolescents and young adults in the United States is ∼9.2 million; however, a more concerning statistic is the number of incident infections that are acquired by this age group. Estimates suggest that ∼75% of all new infections, or 4.6 million cases annually, occur among men and women 15–24 years of age (Fig. 6).29FIGURE 5.: Estimated percentage of the population exposed to HPV.18FIGURE 6.: Annual incidence of common sexually transmitted infections among Americans 15–24 years old. HPV causes an estimated 4.6 million new infections annually among young men and women.29Several epidemiologic studies have reported on the prevalence of HPV infection among adolescent and young adult populations. Overall the highest prevalence of HPV infection has been identified in sexually active women 25 years of age and younger (Fig. 7). 2 In an early study, 213 of 467 (47%) University of California-Berkeley students (mean age, 22.9 years) tested positive for cervical or vulvar HPV DNA.31 More recent studies involving younger girls (12–21 years) have reported prevalence rates of cervical HPV infection to be between 51 and 64%.32,33 In 2005, Brown et al34 showed that 49 of 60, or 82% of adolescents 14–17 years of age tested positive for cervicovaginal HPV during a 27-month study.34 Overall, these studies highlight the extent of HPV infection among adolescents and young adults.FIGURE 7.: Estimated age-specific prevalence of high risk HPV infections among women in Portland, OR.2Well-designed natural history studies of HPV infection in high risk populations have shed key insights on associated transmission and risk factors. A comprehensive study of college women in the state of Washington compared the frequency of infection among sexually active women who were initially HPV-negative with that of virgins who had decided to initiate sexual intercourse. The cumulative 24-month incidence rates were 38.8 and 38.9% for nonvirgins and virgins, respectively.35 Overall >60% of women acquired HPV infection within 60 months of enrolling in the study (Fig. 8). Another study of college women reported a similar rate in that 36% of women acquired new HPV infections within 24 months of enrolling in the study.36 In a separate study of recently sexually active adolescents, the cumulative incidence rate of new HPV infections among initially HPV-negative women 15–19 years of age was 44% during a 36-month period.37 Lastly, in a study following women attending family planning clinics in the San Francisco area, ∼55% of initially HPV-negative women 13–21 years of age acquired HPV within 36 months of enrollment.38 The strongest risk for acquiring HPV was reporting a recent new sexual partner. For each new sexual partner in the month preceding, the increased risk for HPV incidence was 10-fold. In a college population, an increased number of sexual partners was directly correlated with increased prevalence of HPV infection: 20% of women reporting one lifetime sex partner were infected with HPV, whereas 55% of women reporting 4–5 partners were infected.31 In summary, we can estimate that approximately half of all sexually active adolescents and young men and women will acquire HPV infection within 5 years of initiating intercourse. These rates support the ease of sexual transmission and strongly suggest that sexual activity is the most important risk factor for acquiring HPV infection.FIGURE 8.: Cumulative incidence of HPV infections among women (A) initially HPV negative and (B) among recently sexually active virgins.35Other risk factors include younger ages of first sexual intercourse, smoking, oral contraceptive use,39 and a history of herpes simplex virus (HSV).38 Not surprisingly, a history of genital warts is also associated with an increased risk of cervical HPV infection.38 Findings with HSV are not surprising because HSV can cause inflammation and breaks in the mucosa, allowing HPV access to the basal epithelium. Although the precise mechanisms by which these risk factors influence acquisition of HPV infection are not known, most can be associated with sexual behavior and are therefore indirectly linked to an increased risk of infection. Incidence of HPV-Associated Disease in Adolescents and Young Adults When we assess the entire population, we find that adolescents and young adults are most at risk for developing low grade cytologic abnormalities. Indeed both HPV prevalence and incidence of LSIL are highest among women younger than 25 years of age (Fig. 9). 40,41 Between 20 and 40% of young women infected with HPV develop LSIL within 60 months of acquiring HPV infection (Fig. 10). 38,42 Although high incidence rates of LSIL are presumed to be a result of high prevalence of HPV in this population, it has been hypothesized that younger women may be at an increased risk because of normal cervical development following menarche.43 During cervical maturation, the squamous columnar junction of the cervix naturally undergoes squamous metaplasia, a process of rapid cell differentiation and replication. This type of epithelium is a natural host to HPV because it requires both cell differentiation and replication to sustain protein expression and viral replication. As such, the developing squamous epithelium can be more susceptible to infection with HPV in young women.42 Overall, approximately one-quarter of HPV-infected adolescents and young women will develop low grade cervical lesions; however, the majority (>70%) of low grade lesions diagnosed in young women will spontaneously regress within 3 years of diagnosis.44 The regression of LSIL and the implications for cervical cancer screening of adolescents will be discussed in a separate section. One exception to the high rate of regression is among patients who are immunocompromised, including iatrogenically immunosuppressed transplant recipients and HIV-infected men and women. Presumably because of increased HPV persistence,45 these patients are at a significantly increased risk of developing advanced stage HPV-associated diseases.46,47 Immunocompromised patients should be closely monitored for the development of high grade lesions and cared for appropriately.FIGURE 9.: Age-specific prevalence of LSIL, HSIL and cervical cancer.40FIGURE 10.: Estimated time young women infected with HPV remained free of LSIL.38Genital wart rates are also highest among young adults. Incidence rates for genital warts among men and women are nearly identical, with rates peaking for women between 20 and 24 years of age and for men between 25 and 29 years of age.48 However, incidence rates among girls increased >6-fold between the age groups of 10–14 years and 15–19 years. Thus, as with HPV infections and the development of cervical lesions, genital warts are most commonly diagnosed among adolescents and young adults. The Role of Condom Use in the Transmission of HPV and the Development of HPV-Associated Diseases It has been hypothesized that HPV rarely infects the cervix in the absence of intromissive sexual intercourse but that HPV can be easily transmitted to the vaginal introitus or external genitalia in the absence of sexual intercourse.35 Thus women who engage in intromissive sexual intercourse will most likely test positive for both cervical and vulvovaginal HPV, whereas women who do not will most likely test positive only for external anogenital HPV. In support of this argument, HPV DNA was detected at the vulva in 20% of virginal women, whereas no HPV DNA was observed in these women on the cervix.31 Thus cervical infection, like vulvar infection, most likely requires direct contact from the source. Whether condoms protect the cervix remains controversial, and many individuals who claim to use condoms use them inconsistently and often not during foreplay. A meta-analysis of 20 studies was conducted to determine whether condom use is protective against HPV infection or development of HPV-associated disease. The overall conclusions from the study were that condom use does not completely protect against acquiring HPV infection but that condoms provide some level of protection against the development and/or persistence of HPV-associated disease.49 In a study that followed HPV infection among Danish sex workers, women who used condoms were 80% less likely to have evidence of cervical HPV infection than those who did not.50 Nonetheless HPV commonly infects areas that are outside of those areas covered by a condom. Patients should be informed that condoms may provide some level of protection against infection of the cervix; however, they do not fully protect against infection of other external anogenital areas. This is true of many STIs, and condoms do break; thus most importantly, patients should be urged to use condoms consistently and during all forms of sexual contact. Several studies have suggested that condom use reduces the incidence of HPV-associated diseases and possibly aids in lesion regression. For example, young men who reported always using condoms were 70% less likely to develop genital warts than those who did not use condoms.51 In a separate study, men and women who reported using condoms were 60% less likely to be diagnosed with genital warts.49,52 Similar reductions have been seen for cervical dysplasia. In a study by Wang and Lin,53 women reporting condom use were 70% less likely to have high grade lesions than those who did not use condoms. Also women who reported always using condoms were determined to have a reduced risk of developing LSIL (relative hazard, 0.82).38 Interestingly one study has shown that condom use reduces persistence of HPV infection and aids in lesion regression. In this randomized study, women diagnosed with cervical intraepithelial neoplasia (CIN) who were randomized to condom use showed a 2-year cumulative regression rate of 53% versus only 35% for women who did not.54 The mechanisms by which condom use promotes lesion regression are not fully understood; however, condoms may decrease the amount of virus transmitted, thereby decreasing infectious viral load. Condoms may also decrease the incidence of other STIs that may be cofactors in the development of higher grade lesions. These decreases may indirectly aid in lesion regression and prevent the development of new HPV-associated lesions. CONSENSUS 3: THERE IS A NEED FOR UNDERSTANDING THE LESSER SIGNIFICANCE OF HPV DETECTION AS OPPOSED TO DETECTION OF HPV-ASSOCIATED DISEASE Many women will become infected with high risk HPV types, but in the absence of intervention only ∼2% will develop precancerous lesions that might progress to cancer. Persistent infection with high risk HPV types is a major determinant for developing high grade preinvasive cervical lesions. High Risk HPV Types are the Most Common Infections It is well-documented that HPV is highly prevalent and that most sexually active individuals will become exposed to HPV at some point in their lives.30 Furthermore many studies have conclusively shown that high risk HPV types are the most common HPV infections observed.55 Nonetheless very few individuals will ever develop premalignant or malignant anogenital disease. Understanding the significance of detection of HPV is of utmost importance for clinicians and health care providers who provide gynecologic care for women of all ages. In a study of nearly 10,000 women, high risk HPV infections were observed more often than low risk infections.40 Furthermore, among women 18–54 years of age, the prevalence of low risk types was consistently lower than that observed for high risk types in each age group (Fig. 11). In a separate study of mostly college age women (mean age, 23 years), baseline prevalence for high risk HPV types was 22% versus 15% for low risk types.36 Moreover the incidence of high risk infections was 14.0 per 1000 women-months compared with 12.4 per 1000 women-months for low risk types. Finally, in a study of women attending family planning clinics in San Francisco, 46% of all incident infections were classified as high risk, whereas only 9% were low risk (13% were mixed with high and low risk and 32% were nonstandard HPV types).38 Of high risk HPV types, HPV 16 is responsible for >50% of all diagnosed cervical cancers and is by far the most common HPV infection.5 In asymptomatic women, the prevalence of HPV 16 alone has been reported to range from 19% to 38% of all infections.36,37,55FIGURE 11.: Age-specific prevalence of high and low risk HPV infections.40Most HPV Infections, Both Low and High Risk Types, Are Efficiently Cleared Of the many natural history studies, each has concluded that persistence of HPV infection, often defined as detection of HPV DNA of the same HPV type among 2 or more consecutive tests (at least 6 months apart), is the main risk factor for developing cervical cancer.56 This explains why HPV infections rarely cause advanced stage disease because most infections are transient. The transient nature of infection is true for both low and high risk HPV types. Studies show that 70–90% of infections will clear within 36 months. In one study, the average time to clearance of high and low risk HPV infections was 8.9 and 7.0 months, respectively (Fig. 12). 55 Other studies have reported longer retention times of 17.4 months and 15.8 months, respectively; however, in most studies, nearly all HPV infections become undetectable by sensitive molecular tests within 2–3 years.34,36,42FIGURE 12.: Time to clearance of oncogenic and nononcogenic HPV infections. The average time to clearance was 7.0 and 8.9 months for low and high risk HPV types, respectively.55The reasons for spontaneous regression of active infection are not fully understood. Certainly the cellular immune system is involved in controlling HPV infections; however, it is also possible that the life cycle of HPV, by itself, is inherently self-limiting. Others have suggested that the immune system forces the virus into a state of long-term latency. This mode of viral suppression is more concerning because the virus would be able to reactivate and cause persistent infection as infected individuals age and their immune systems naturally wane.57 Understanding the immune response to HPV infection is an area of intense research and should shed key insights into the mechanisms behind the spontaneous clearance of HPV in infected individuals. Nevertheless, because most infections are efficiently cleared or suppressed, clinicians should take care when explaining the results of HPV DNA tests to infected patients and stress that persistent infection, or continuous detection of HPV, is associated with developing high grade lesions, whereas incident infections that are efficiently cleared by the immune system are not associated with disease. Most HPV-Associated Lesions Will Not Progress to Invasive Cancer The development of cervical cancer is thought to involve many factors, of which persistent infection with high risk HPV is central to carcinogenesis (Fig. 13). 58 Similar to regression of infections, most HPV-associated lesions will spontaneously regress. However, probability of regression is directly related to the histologic diagnosis. A recent metaanalysis of 15 natural history studies that followed >25,000 women who were diagnosed with atypia or worse was performed to determine rates of lesion regression over time.59 Among all women, 68% of cytologies diagnosed as atypical squamous cells of undetermined significance (ASCUS), 47% of LSIL cytologies and 35% of HSIL cytologies regressed to normal. Furthermore <2% of ASCUS, 6.6% of LSIL and 6.8% of HSIL progressed to more advanced lesions during a 6-month period. Rates for progression to invasive cancer were even lower: 0.06, 0.04 and 0.15% for ASCUS, LSIL and HSIL cytologies during a 6-month period, respectively. Other studies have reported similar findings.60 Of note, lesions that contain high risk HPV types, specifically HPV 16, or lesions with mu