Human Papilloma Virus (HPV) infection can be reduced by avoiding many sexual partners.

While a considerable amount of information exists regarding the molecular epidemiology of genital HPV infection in women, there is a significant gap in our understanding of the likelihood of re-infection with HPV, particularly with the same type. Limited data is available on the source of HPV infection in older women, specifically those aged 40 and above. Two competing hypotheses attempt to explain the occurrence of ostensibly incident HPV infections in such women.

 

The first hypothesis operates under the assumption that infections acquired at a young age do not completely clear but rather become latent. In this scenario, infections manifesting later in life would largely be reactivations of latent infections acquired many years earlier. These reactivations might be triggered by various non-mutually exclusive factors, such as hormonal changes during the peri-menopausal period or a decline in cellular and humoral immunity against the original HPV types. The second hypothesis revolves around the idea that infections do clear after an initial immune response, which, however, does not provide complete protection against future infections by the same HPV type. This leaves individuals susceptible to new exposures later in life, possibly through sexual activity.

 

Determining whether an infection represents a genuine new episode or the reactivation of a latent and previously undetected earlier infection is crucial for justifying the vaccination of adult women, especially those in older age groups, against HPV. Since vaccination is predominantly prophylactic and not therapeutic, understanding whether an infection is a new occurrence or a reactivation is essential for assessing the efficacy of vaccination. It clarifies whether vaccination can offer protection against new infections but not against latent ones.

 

Worse still sex between men and women who are older than 30 years increases the risk of cancer as the immune system  of many individuals is less efficient after age 30years.

Is there a link between the number of sexual partners and cancer?

Published in BMJ Sexual & Reproductive Health, the investigation involved approximately 2,500 men and 3,200 women aged 50 or older, with an average age of 64. Participants were surveyed about their lifetime sexual partners, and this data was juxtaposed with various medical conditions they had experienced, such as cancer, heart disease, and stroke.

 

The study revealed that:

•        Men who reported 10 or more sexual partners in their lifetime were nearly 70% more likely to have developed cancer compared to those reporting 0 or 1 lifetime sexual partner.

•        For women, the results were even more striking: those who reported 10 or more sexual partners in their lifetime were nearly 91% more likely to have developed cancer compared to those reporting 0 or 1 lifetime sexual partner.

 

The disparity between men and women was notable, with men more likely to report having at least 10 partners (22% of men vs. 8% of women), while women were more likely to have fewer partners (41% of women and 28.5% of men reported having 0 to 1 partners).

 

It is important to consider that this study was conducted in England, with health data initially collected in the late 1990s. The results might vary if researchers assessed a different population or conducted the study at a different time. Additionally, the reliance on self-reporting to assess sexual behavior raises the possibility that the reported number of sexual partners and other health behaviors may not be entirely accurate.

 

Sex education should target age related variables of HPV infection with emphasis on protection for sexual intercourse after years.

Human Papillomavirus (HPV) stands out as one of the most prevalent sexually transmitted infections affecting sexually active adolescents and young individuals worldwide. Typically transmitted through sexual contact [1] and direct skin-to-skin contact, the primary mode of transmission is often via penetrative sex.

 

Individuals engaging in sexual activity, both men and women, face susceptibility to acquiring genital HPV infection, with a lifetime risk reaching up to 80%. Fortunately, the majority of these infections (up to 90%) naturally clear within 2 years (12–24 months), with only a minority persisting [3]. Initial HPV infections frequently occur shortly after the onset of first sexual intercourse (FSI), leading to a cumulative genital HPV infection rate of approximately 50% over a span of 3 years after the initial intercourse. The prevalence of HPV infection is most prominent among young women (18–24 years) in the early stages of sexual activity. This prevalence gradually declines with age until the 4th-5th decade, where a second peak occurs due to hormonal changes during perimenopause, followed by another decline [6]. Young individuals are more exposed to HPV infection due to their sexual behavior, and younger women are more susceptible than their older counterparts, primarily because of the cervical ectopy location of the transformation zone on the ectocervix.

 

The risk of developing precancerous lesions amplifies with persistent HPV infections [8]. Persistent infection with an oncogenic HPV type serves as a prerequisite for the development of cervical cancer [9] and can also be implicated in cancers at other anatomical sites, including the anus, vagina, vulva, oral cavity, and oropharynx.

 

Several prevalent risk factors contribute to HPV infection and its persistence in the population, encompassing early initiation of sexual activity, the number of lifetime sexual partners, frequency of sexual or other intimate skin-to-skin contact, sexual histories and behaviors of partners, cigarette smoking, parity, certain types of oral contraceptive use, and alcohol consumption.

 

Does the HPV virus mutate in the same host, maybe.

A recent examination of genital human papillomavirus (HPV) in men reveals a notable risk of reinfection with the same HPV type, particularly when infected with the type responsible for most HPV-related cancers. Specifically, men carrying the type associated with the majority of HPV-related cancers are 20 times more likely to experience reinfection within a year. This heightened risk implies that an initial infection does not confer natural immunity against HPV, a departure from the immunity often observed with other viruses.

 

Published on December 5 in the Proceedings of the National Academy of Sciences, the study underscores the significance of vaccination in preventing the transmission of HPV among young men before they initiate sexual activity. Furthermore, vaccination may offer potential in preventing reinfection in older men who have previously contracted the virus.

 

The efficacy of vaccinating boys prior to HPV exposure emerges as a highly promising strategy to reduce the prevalence of HPV infection. Additionally, vaccinating men with a history of infection may prove effective in preventing further instances of the virus.

 

HPV stands as the most prevalent sexually transmitted infection, affecting approximately 40 percent of women and 45 percent of men in the United States. It plays a significant role in causing genital warts and cancers affecting the genitals, mouth, and throat. With over 200 genetically distinct HPV types, vaccines currently protect against four to nine of the most common disease-causing types.

 

Researchers, including Ranjeva and colleagues at the University of Chicago, including Greg Dwyer, PhD, professor of ecology and evolution, and Sarah Cobey, PhD, assistant professor of ecology and evolution, sought to comprehend the factors facilitating the coexistence of numerous HPV types. Their analysis drew from data on the spread of the disease collected during the HPV in Men study, tracking over 4,000 unvaccinated men across three cities in Florida, Mexico, and Brazil over a five-year period from 2005 to 2009.

 

Typically, the diversity observed in various virus types arises from their competition to evolve and employ distinct strategies to elude the immune defenses of hosts. However, the recent analysis revealed no signs of such competition among HPV types. Instead, the diversity of HPV types seems to result from recurrent infections of specific types within individuals. Although each type infects relatively few individuals, the overall high prevalence of HPV occurs because nearly half of the adult population carries at least one type of genital HPV. The heightened risk of reinfection may be attributed to either auto-inoculation, where the infection spreads through repeated contact between different body sites, or reactivation of a latent virus.

 

The findings also indicate that men who contract HPV16, the type responsible for most HPV-related cancers, face a 20 times higher risk of reinfection after one year and a 14 times higher risk after two years. Interestingly, this pattern holds true for both sexually active and celibate men, suggesting that they are not acquiring the virus from another sexual partner.

 

HPV is linked to various clinical conditions ranging from benign lesions to cancer (refer to Table 1). Initially recognized as the cause of cutaneous warts on the hands and feet, HPV infections are generally benign, with warts resolving spontaneously within 1 to 5 years. Certain strains targeting the face increase the likelihood of skin cancer. Others, growing primarily in the oral lining, can develop into fatal squamous cell cancers. Focal epithelial hyperplasia of the oral cavity (Heck's disease), mainly caused by HPV-13, tends to regress spontaneously. Epidermodysplasia veruciformis, a rare genetic disease with HPV-associated warts on the trunk and upper extremities, can progress into invasive squamous cell carcinomas. Conjunctival papillomas and carcinomas associated with HPV have been documented. Recurrent respiratory papillomatosis, primarily affecting the larynx in young children, is thought to be acquired during childbirth, with a high percentage of mothers having a history of HPV. Malignant transformation may occur in respiratory tract lesions.

 

Cervical cancer ranks as the third most prevalent cancer among women in the United States, following skin cancer and breast cancer as the first and second leading causes, respectively (93). In developing nations, cervical cancer often takes the forefront as the most common cancer in women, constituting up to 25% of all female cancers (45). Globally, cervical cancer stands as the second most common cause of cancer-related deaths in women, preceded only by breast cancer (54). The association between genital HPV infections and cervical cancer was initially established by Harold zur Hausen, a German virologist, in the early 1980s. Since then, the connection between HPV and cervical squamous cell carcinoma has been firmly established, surpassing the magnitude of the association between smoking and lung cancer (37).

 

In 1996, the World Health Association, in collaboration with the European Research Organization on Genital Infection and Neoplasia and the National Institutes of Health Consensus Conference on Cervical Cancer, acknowledged HPV as a significant cause of cervical cancer. Approximately 30 HPV types, primarily transmitted through sexual contact, infect the cervix, vagina, vulva, penis, and anus. Among these, four are frequently found in the malignant cells of cervical cancers, with type 16 contributing to about half of the cases in the United States and Europe, while types 18, 31, and 45 account for an additional 25 to 30% of cases (45). HPV has been implicated in 99.7% of cervical squamous cell cancer cases globally (124). Although adenocarcinomas of the cervix are also linked to HPV, the correlation is less prominent and varies with age. In women under 40 years old, HPV was present in 89% of adenocarcinomas, while in women aged 60 years and older, HPV was observed in only 43%.

 The primary mode of HPV transmission occurs through skin-to-skin contact, and epidemiological studies confirm that sexual activity significantly influences the risk of contracting genital HPV infection and cervical cancer. HPV exhibits high resistance to heat and desiccation, allowing nonsexual transmission through fomites, such as prolonged exposure to contaminated shared clothing (94). Increased vulnerability to HPV infection is associated with factors such as having multiple sexual partners, engaging with individuals who have had multiple partners, early onset of sexual activity, a history of other sexually transmitted diseases, genital warts, abnormal Pap smears, or a history of cervical or penile cancer in oneself or one's sexual partner. Condom usage may not offer comprehensive protection against HPV, as the virus can be transmitted through contact with infected labial, scrotal, or anal tissues that remain unprotected by a condom.

 

In addition to sexual activity, age is a crucial determinant of HPV infection risk (1, 18). Most cervical cancers originate at the squamocolumnar junction, where metaplastic changes are continuous. The highest risk of HPV infection aligns with periods of significant metaplastic activity, such as puberty and first pregnancy, declining after menopause. HPV infection is most prevalent in sexually active young women, particularly those aged 18 to 30, with a marked decrease in prevalence after the age of 30. Despite this decline, cervical cancer is more common in women over 35, suggesting infection at a younger age with a slow progression to cancer. Persistence of infection, especially with high-risk oncogenic HPV types, is a critical factor in cervical cancer development.

 

Although the detection of high-risk HPV is essential, it may not alone be adequate for the development of cervical cancer. Various factors, including compromised cell-mediated immunity resulting from conditions such as renal transplantation or human immunodeficiency virus disease, contribute to the process leading to cervical cancer. The upstream regulatory region of HPV shares sequences with glucocorticoid responsive elements inducible by steroid hormones like progesterone (found in oral contraceptives) and dexamethasone. The extended use of oral contraceptives is considered a significant risk factor for high-grade cervical disease in some studies but not in others. Independent risk factors for cervical cancer encompass current smoking and parity, with smoking being a pivotal risk factor for higher grades of cervical disease. Multiple pregnancies also emerge as a significant independent risk factor, especially among women with histopathologic evidence of HPV infection in biopsy specimens and those with moderate- to high-grade cervical disease. The impact of factors like alcohol consumption and diet on contributing risks has not been conclusively established.

 

There has been speculation about sexually transmitted viruses serving as cofactors in the development of cervical cancer. It has been postulated that coinfection with herpes simplex virus type 2 may play a role in initiating cervical cancer (131). Cytomegalovirus (CMV), human herpesvirus 6 (HHV-6), and HHV-7 have been detected in the cervix. Coinfection provides the opportunity for these viruses to interact with HPV. Putative oncogenes and transforming factors have been suggested for CMV and HHV-6, but epidemiologic and in vitro data do not conclusively support a causal association with cervical cancer (23, 89, 95, 102). Recent studies using PCR to detect CMV, HHV-6, and HHV-7 in women with abnormal cervical cytologic test results indicate that these viruses are more likely bystanders than cofactors in the development of cervical cancer (21).

 

The proposition that viral load directly corresponds to the severity of the disease has been explored. Studies utilizing quantitative type-specific PCR for high-risk HPV types, including -16, -18, -31, -33, and -45, as well as low-risk types -6 and -11, demonstrate that HPV-16 can achieve substantially higher viral loads than other types. Significantly, only in the case of HPV-16 does an elevated viral load correlate with increased severity of cervical disease (111, 130). All types of high-risk HPVs possess the capability to induce malignant tumors, even when present at low levels (132).

 

An increasingly crucial factor in the development of cervical neoplasia is the role of HPV variants (39). These variants exhibit differences in biological and chemical properties, as well as pathogenicity (27, 120). Based on sequence variations in the L1, L2, and LCR regions of HPV-16, five naturally occurring phylogenetic clusters have been identified: European (E), Asian (As), Asian-American (AA), African-1 (Af1), and African-2 (Af2). Intrapathogenic sequence variations have also been observed in the E2, E4, E5, E6, and E7 genes of HPV-16. Given that the LCR contains E2 binding sites and binding sites for various transcription factors, nucleotide sequence variations in the LCR, E2, E6, and E7 genes may hold functional significance. The oncogenicity of specific HPV variants appears to vary geographically and with the ethnic origin of the population studied. For instance, an investigation suggested that due to increased transcriptional activity and alterations in progesterone response elements, Asian-American variants might exhibit enhanced oncogenic activity compared to European isolates (120). European HPV variants with point mutations in the LCR binding sites demonstrate enhanced transcriptional activity compared to the European prototype (32). In a large clinical study involving 10,000 women in Costa Rica, the European HPV-16 prototype and three variants were identified (46). The most prevalent variant, EP[a], featured a single point mutation and was not associated with disease. A second variant, EL, exhibited single point mutations at locations distinct from EP[a] and was linked to normal cytology and some high-grade squamous intraepithelial lesions (HSILs). Another variant, NE, showcased multiple substitutions within the LCR and was associated with HSIL and cancer at rates much higher than expected. The mechanisms behind this association remain unknown, and given the complexity of transformation, mutations might directly impact transcription by increasing promoter activity, influence other regions of the viral genome, or affect the relationship between HPV variants and nonviral factors such as HLA and p53. The study also reported a

 

 statistically significant association of the NE variant with the presence of HLA class II alleles. Although other studies have noted associations between HLA class II alleles and cervical HPV disease, these associations appear relatively weak (2, 5, 13). Intratypic sequence variation has also been scrutinized for other high- and intermediate-risk HPV types, as well as low-risk types 6 and 11. Notably, sequence variation in low-risk types was not linked to increased activity of the promoters responsible for E6 and E7 protein expression (39).

 

A genetic predisposition to colorectal cancer, lung cancer, and melanoma has long been recognized and is widely accepted. Genetic predisposition was found to be an even greater component in cervical cancer when the same method of analysis was used (73). Genetic heritability was found to account for 27% of the effect of underlying factors for tumor development. Heritability could affect many factors contributing to the development of cervical cancer, including susceptibility to HPV infection, ability to clear HPV infection, and time to development of disease. The effect of shared familial environment was shown to be small at 2% and was found only between sisters and not between mother and daughter.

 

Studies have shown that infections with multiple types of HPV can occur (52, 59, 88). Multiple-infection rates up to 39% have been seen. The presence of multiple HPV genotypes tended to increase with the severity of cervical disease. Multiple genotypes, usually with at least one type classified as high risk, were found in 11.8% of patients with normal cytology or ASCUS (see below) and in 34.5% of patients with mild or moderate dyskaryosis (59). However, the prevalence of multiple genotypes was much lower in cervical carcinoma tissue samples (4.4%) (59). The majority of multiple infections contain two HPV genotypes, but samples with three, four, or five genotypes were also seen (52, 88).

 

Coinfection with adeno-associated virus is associated with a significantly reduced risk of cervical neoplasia (26). Adeno-associated virus replication gene product Rep78 disrupts the transcription of the HPV-16 E6 and E7 oncogenes by interfering with the binding of the TATA binding protein to the p97 core promoter in the LCR region of the HPV genome (110). This interference does not require HPV gene products.

 

 

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