#53384: Women's Health for Dental Professionals

Vaginitis is caused by a wide variety of organisms. These organisms can produce symptoms such as burning, itching, and vaginal discharge. Asymptomatic colonization may occur as well. Trends suggest that the incidence of yeast infections in particular is increasing, in part because of the widespread use of antimicrobial therapy. An estimated 75% of women will have at least one episode of vulvovaginal candidiasis, and 40% to 50% will have two or more episodes [21]. The organism most often responsible for vulvovaginal candidiasis is the fungus Candida albicans. Other species (e.g., C. glabrata and C. tropicalis) may also cause vulvovaginal candidiasis and are more resistant to treatment [22]. Vulvovaginal candidiasis is also commonly called moniliasis or referred to as a yeast infection [21,23,24,25].

A growing number of healthy, asymptomatic women now harbor C. albicans. A change in the vaginal environment and pH may cause the candida organisms to grow, resulting in the symptoms of vaginitis. The risk of yeast infections increases when women take an antibiotic for an infection in another part of the body that inadvertently impacts the balance of the normal flora of the vagina. Because these bacteria, by their presence, limit growth of Candida, their elimination may result in proliferation and the clinical signs and symptoms of a yeast infection [21,22,23,24,26].

This issue is particularly relevant for dentists if they routinely prescribe broad-spectrum antibiotics. As a result of research and education efforts, most dentists, as well as many of their patients, are aware of the risk of the development of a yeast infection when using broad-spectrum antimicrobial agents. Subsequently, these drugs are being prescribed less often than in the past. It is important to note that some women are more prone to develop yeast infections than other women and may do so even when antibiotics are not taken.

Endometriosis is a condition in which cells from the uterine lining are found in other locations within the pelvic cavity. In women with endometriosis, endometrial cells have traveled through the fallopian tubes and implanted on other structures, such as the bladder, rectum, ovaries, and the outside surfaces of the uterus, vulva, and vagina. The exact incidence of endometriosis is unknown, but as many as 33% of women seen for pelvic pain, infertility, or pelvic mass are ultimately diagnosed with endometriosis [27]. The symptoms are caused by changes in the endometrial patches with the hormonal cycle. These patches thicken and bleed just like normally functioning endometrial tissues. The symptoms increase in severity over the years as the patches grow. Women with endometriosis often complain of pain, pelvic heaviness, hypermenorrhea, and pain radiating to the thighs. Scar tissue, infertility, and distortion or blockage of the affected structures may result.

The diagnosis of endometriosis is confirmed by laparoscopic identification of the patches. Treatment options vary, depending on the severity of the condition and the woman's childbearing choices. Because endometriosis may cause infertility, treatment should not be greatly delayed when childbearing is desired. Oral contraceptives are often helpful, as is treatment with danazol. Mild endometriosis is treated by surgically removing the endometrial patches. Women with severe endometriosis who do not wish to have children may consider hysterectomy [28].

While infant mortality rates have declined, low birth weight in preterm infants remains a significant cause of infant morbidity and mortality. In spite of increased efforts to diminish these outcomes through preventive interventions during prenatal care that addresses traditional risk factors, these efforts appear to have only a minimal impact on the number of preterm low-birth-weight (PLBW) infants, with some research indicating weight increases of less than 1% [61]. Researchers are thereby investigating other, previously unrecognized risk factors that may contribute to the continuing prevalence of PLBW infants.

A number of studies have indicated that women with periodontal disease have an increased risk of preterm births [18,62,63,64]. A PLBW baby is defined as one born before the 37th week of gestation, weighing less than five pounds, six ounces. In a study of 124 pregnant or postpartum mothers at the University of North Carolina School of Dentistry, those who delivered preterm newborns were more likely to have significantly worse periodontal disease than a comparable group of women who delivered normal birth weight infants. The researchers concluded that periodontal disease is a statistically significant risk factor for preterm low birth weight, with an adjusted odds ratio of 7.9 [62]. Another study of 870 women with pregnancy-associated gingivitis conducted by the Department of Conservative Dentistry in Santiago, Chile, found that periodontal treatment significantly reduced the incidence of preterm labor and/or low birth weight infants [65]. However, the results of more recent studies find limited and/or insufficient evidence to conclude that periodontal disease or its treatment led to a reduction in PLBW infants [66,67]. Nevertheless, the American Academy of Periodontology has recommended that periodontal evaluations be a part of a woman's overall healthcare program as periodontal disease can impact a woman's health in a variety of ways throughout her life [68].

Although ongoing studies are exploring the way in which oral infections may trigger preterm births, several pieces of the puzzle have been postulated as to how the disease may affect delivery timing. For example, other types of maternal infections, including genitourinary infections, have been linked to premature labor, and certain bacteria similar to organisms associated with periodontal disease have been detected in the genital tracts of women at a higher risk for preterm birth. Within the oral cavity, periodontal plaque triggers an inflammatory process that leads to increases in levels of a number of substances, including prostaglandin E2 (PGE2) and tumor necrosis factor-alpha (TNF-a) molecules. The elevated presence of PGE2 can yield a molecule whose configuration is quite similar to oxytocin, which can induce labor. Thus, the presence of chemicals such as PGE2 may trigger preterm delivery [16,69]. A study found that maternal periodontal disease is associated with systemic inflammation and elevated serum C-reactive protein (CRP) levels, a marker of inflammatory processes, and other studies have shown that a very high CRP level early in pregnancy is a risk factor for preterm delivery [70,71]. One case-control study investigated the utility of inflammation markers as predictors of preterm birth by exploring longitudinal changes in interleukin (IL)-1B, IL-6, IL-10, TNF-a, and CRP in pregnant women [72]. Results indicate that maternal inflammation markers, particularly IL-6 and IL-10, are associated with increased risk of preterm birth, with associations varying by etiology of preterm delivery and gestational age at sample collection [72].

The relationship between infection, especially genitourinary infections, and adverse pregnancy outcomes has been well documented in both animal and human studies. University of North Carolina researchers found that gingival crevicular fluid levels of PGE2 are significantly elevated in mothers of preterm low-birth-weight infants, compared with mothers of normal birth weight controls. Specifically, four micro-organisms associated with progressing periodontitis (i.e., Bacteroides forsythus, P. gingivalis, Actinobacillus actinomycetemcomitans, and Treponema denticola) were found in greater amounts in the mothers of preterm low birth weight infants, compared to controls [73]. In a separate study at Columbia University School of Dental and Oral Surgery, mothers of low birth weight infants had significantly increased levels of B. forsythus and Campylobacter rectus, as well as consistently higher levels of other species [74]. Results of one study found an association between certain maternal and fetal genes and increased risk of premature birth when mothers are exposed to urinary tract or vaginal infection [75].

A number of other factors are known to contribute to the incidence of preterm infants, which, in 2021, accounted for 10.5% of all live births [76]. It has also been reported that preterm births account for 35% of all U.S. healthcare spending for infants and 10% of spending for children as a whole [77]. In 2016, the average first-year medical costs (inpatient and outpatient care) were approximately four times greater for preterm ($49,140) than for term infants ($13,024) [76]. Widely acknowledged risk factors include a poor diet, maternal age younger than 20 years or older than 35 years, multifetal pregnancies, various maternal health problems (e.g., high blood pressure, diabetes), and maternal intake of alcohol, nicotine, or drugs [78]. The conclusions of a study conducted by the University of Alabama at Birmingham School of Dentistry led researchers to report that "poor periodontal health of the mother is a potential independent risk factor" for low-birth-weight infants [79]. This finding has also been reported by other researchers [78,80].

Treatment of periodontal disease in pregnant women, and in all women of childbearing age, could have a positive effect upon the incidence of preterm births, although evidence of this benefit is still scarce. Intervention studies have begun at several universities that should shed greater light on the interrelationship and how it may be favorably influenced [61]. The Columbia University researchers cited above found that 19.9% of women who did not receive periodontal intervention gave birth to PLBW infants, compared to 13.5% of women who did receive the therapy [74]. One study that included 586 women (148 PLBW infants, 438 full-term infants) found that the extent and severity of periodontal disease appears to be associated with increased risk of PLBW delivery [81].

Commonly known as severe "morning sickness," hyperemesis gravidarum is thought to be caused by hormones released by the placenta and is characterized by severe nausea and vomiting during pregnancy, which repeatedly exposes tooth enamel to gastric acid [82,83]. Later in pregnancy, the enlarged uterus can exert pressure on the stomach and exacerbate acid reflux. Patients with hyperemesis may have enamel erosions.

Strategies to avoiding nausea, vomiting, and therefore oral acid exposure during pregnancy include dietary and lifestyle changes, such as reduction of exposure to hot showers; strong smells or flavors; bright or blinking lights; motion, such as riding in a car; and pressure on the stomach from tight clothing [82]. Antiemetics and/or antacids may also be prescribed.

A rinse made with one teaspoon of baking soda dissolved in 8 ounces of water should be used to neutralize acid in the oral cavity after vomiting. Tooth brushing should be delayed for several hours to protect the softened enamel. A soft-bristled toothbrush should be used to reduce damage to the enamel as long as the condition continues [83].

Although the exact cause of cervical cancer is unknown, cervical cell changes may be the result of an "insult" from viruses and multiple sexual partners. Women with cervical cancer often report a history of cervical infections. The infections most frequently linked to cervical carcinoma are caused by herpes simplex virus type 2 (HSV-2); human papillomavirus (HPV) types 16, 18, 45, and 58; human immunodeficiency syndrome (HIV); and perhaps cytomegalovirus. However, HPV infection is almost always the cause of cervical cancer. These viruses alter the DNA in the nuclei of immature cervical cells[85,86,87,88].

The Papanicolaou (Pap) test, or smear, safely and inexpensively detects cervical cancer at an early stage. Dr. George Papanicolaou, a Greek physician, developed the Pap test in the 1940s, and it became a regular component of gynecologic examinations during the 1950s. Since then, the incidence of invasive cervical cancer and the death rate from cervical cancer have declined. The number of women with cervical intraepithelial neoplasia (CIN) had been increasing, but more recent reports indicate declining trends following introduction of HPV vaccination[89,90,91]. As part of general health education, dental health professionals can help ensure that women understand the importance of Pap smears.

Recommendations regarding how frequently average-risk women should have Pap tests have changed significantly as of 2012. National health organizations, such as the National Cancer Institute (NCI) and the American Medical Association (AMA), have adopted consensus recommendations. Other organizations, such as the American Cancer Society (ACS), the American College of Obstetricians and Gynecologists (ACOG), and the U.S. Preventive Services Task Force (USPSTF), have developed updated guidelines for cervical cancer screening. Guidelines from the ACS, the USPSTF, and the ACOG are summarized inTable 1[92,93,94].Management of abnormal cervical cancer screening results should follow current guidelines [95].

In 2006, the U.S. Food and Drug Administration (FDA) approved a quadrivalent HPV (types 6, 11, 16, 18) recombinant vaccine, Gardasil, to prevent vulvar and vaginal precancerous lesions and cervical cancer caused by these strains of HPV. The vaccine is approved for administration in children and adults 9 to 26 years of age[96,97]. This vaccine was the first of its kind to be made available. In 2009, a second HPV vaccine, Cervarix, was approved by the FDA for use in girls and women 10 to 25 years of age[98]. Cervarix protects against HPV strains 16 and 18 and contains a proprietary immune response boosting adjuvant that results in significantly higher serum neutralizing antibody titers compared to Gardasil[99]. In 2014, a 9-valent HPV recombinant vaccine (Gardasil 9) that adds protection to HPV types 31, 33, 45, 52, and 58 in addition to those types covered by the original Gardasil[100]. With this increased coverage, the 9-valent vaccine has the potential to prevent up to 90% of cervical, vulvar, vaginal, and anal cancers. Gardasil 9 is approved for girls and women 9 to 26 years of age and boys 9 to 15 years of age[100]. In 2018, the FDA expanded use of Gardasil 9 to include women and men 27 to 45 years of age[101]. Several other HPV vaccines are in development or clinical trials.

There is hope that HPV vaccination will have a significant positive impact on public health. As discussed, it is uncertain whether vaccination reduces the need for cervical cancer screening, and because neither vaccine provides protection against all HPV strains, both vaccine manufacturers and the Centers for Disease Control and Prevention (CDC) recommend continuation of routine cervical cancer screening[102,103].

It is critical to emphasize to the professional and the public that healthcare appointments are needed for women to be assessed for sexual questions, risk factors, presence of sexually transmitted infections, contraceptive needs, blood pressure, weight control, clinical breast exam, and any other issues of concern.

The most common type of gynecologic cancer is cancer of the uterus, and approximately 66,200 women will be diagnosed with uterine cancer in 2023 [104]. The three layers that comprise the uterus are the inner layer or lining, which is called the endometrium, the middle muscular layer, which is called the myometrium, and the layer of tissue that coats the outside of the uterus, which is known as the serosa. Most uterine cancers begin in the endometrium. Endometrial cancer occurs around 60 years of age on average. Uterine cancer is uncommon in women younger than 45 years of age [104].

Endometrial cancer is familial, and research is underway to identify genetic markers. Research has indicated that a relationship of mismatch repair (MMR) gene mutations to endometrial cancer may be present [105]. MMR genetic abnormalities are also considered causal in hereditary nonpolyposis colorectal cancer (HNPCC), which may be a risk factor for endometrial cancer. Another gene called PTEN, this one responsible for suppressing tumor growth, is often anomalous in women with endometrial cancers [104]. More research is necessary to fully understand the genetics involved in the development of HNPCC-associated uterine cancers.

Risk factors for endometrial cancer include advancing age, hormone imbalance, estrogen therapy, use of birth control pills, intrauterine device use, breast or ovarian cancer, early menarche (before age 12), infertility or no pregnancies, obesity, high-fat diet, diabetes, Lynch syndrome, polycystic ovarian syndrome, and family history [85,104]. The only sign of endometrial cancer, especially in postmenopausal women, is abnormal vaginal bleeding. Women should be instructed to seek treatment when any vaginal bleeding occurs. A pelvic examination with an endometrial biopsy should be performed. If the result of the biopsy is positive, a total abdominal hysterectomy and bilateral salpingo-oophorectomy are performed. Other treatments, depending on the stage of the cancer, include radiation and chemotherapy. These tumors tend to be well differentiated and localized. If the tumors are detected and treated early, women with endometrial cancer have a high survival rate [104,106].

Ovarian cancer is the deadliest of all female reproductive system cancers because it is difficult to detect and diagnose at an early stage [107]. Frequently, by the time it is diagnosed, the cancer has already spread throughout the pelvis. Screening for early ovarian cancer remains a scientific challenge, and new methods are being researched.

Ovarian cancer occurs most frequently between 40 and 70 years of age. The exact cause is unknown; however, evidence suggests a link to endocrine function. Factors preventing ovarian cancer include those that decrease the number of times a woman ovulates. Thus, protection is provided in women who conceive before 25 years of age, experience early menopause, and/or use oral contraceptives for years. Ovarian cancer is familial; if a woman's mother or sister had ovarian cancer, the woman herself is as much as 50% more likely to develop it. Environmental risk factors include talc and asbestos exposure, as well as a high-fat diet. The alarming factor with ovarian cancer is its elusive lack of symptoms. The most common sign is an enlargement of the abdomen [107]. Women may complain of an inability to fasten their pants and skirts. Other symptoms may include vague abdominal fullness or discomfort, pelvic pain, and ascites. Treatment options include surgery, radiation, and chemotherapy. Paclitaxel (Taxol), a newer anticancer medication, has successfully treated progressive ovarian cancer, especially when used in combination with carboplatin (Paraplatin). Another successfully used combination therapy includes cisplatin, etoposide, and bleomycin [108,109]. Target drug therapy with bevacizumab has been shown to shrink or slow the growth of advanced epithelial ovarian cancers. The drug appears to be most effective when used in conjunction with chemotherapy [107].

Breast cancer is the most common cancer in women, but it is also one of the most treatable if detected early. The risk to American women of developing breast cancer in their lifetime is reported as one in eight [110]. Nodal involvement remains the best prognostic indicator for long-term survival. The ACS has reported the five-year survival rate as 99% for localized, 86% for regional, and 29% for distal [111]. These survival rates underscore the importance of rigorous, consistent screening for all women.

The most widely accepted risk factors for breast cancer are age, gender, and personal and family history of breast cancer. The identification of genes associated with familial breast cancer has been a remarkable step forward in identifying risk factors for prevention. However, BRCA1 and BRCA2, the predominant breast cancer genes, only account for 5% to 10% of the breast cancer cases in the United States [112].

In the menopausal and postmenopausal periods, many women experience symptoms in their oral cavity, including dryness of the mouth, pain, burning sensations of the tongue, and changes in taste sensations [18,121,124,125,126,127]. There may be alterations in the oral mucosa as well, including thinning of the epithelial lining. A condition called menopausal gingivostomatitis has been identified, in which the gingiva becomes dry, bleeds easily, and may experience changes in color (from pale to very red) [18,128].

Before menopause, periodontal disease is more common in men than women. But in the postmenopausal years, women surpass men in the incidence of periodontal disease, except women who are on hormone replacement therapy (HRT) (also known as menopausal hormone therapy [MHT]) [129]. When informed that patients have discontinued an HRT regimen, typically because of concerns over the safety of the therapy, dental health professionals should show increased vigilance in detecting and treating periodontal symptoms.

To ease the transition into perimenopause, women should consider the following strategies [130,131,132,133,134,135]:

Research seems to indicate that the loss of bone mass associated with osteoporosis may be associated with the incidence and severity of periodontitis. However, some of these clinical trials have evaluated small numbers of patients, and the control of potentially confounding factors has been inconsistent; the criteria used to define osteoporosis and to assess systemic bone density has also varied [159]. Nonetheless, a 2013 literature review found that 4 of 5 longitudinal studies, 20 of the 25 cross-sectional studies, and all 3 of the case-control studies reviewed showed an association between osteoporosis and periodontal disease [160].

Studies also support a relationship between osteoporosis and clinical attachment loss. While conclusions of the existing trials conflict with one another at times, the general consensus seems to be that an association may exist [159]. A 2022 survey of literature published in the last 25 years indicates that systemic low BMD is associated with alveolar bone loss, while evidence also suggests an association between clinical attachment loss and other parameters of periodontitis [161]. A 2021 study found that patients with osteoporosis and periodontal disease had higher indices of periodontal disease, including tooth mobility and tooth loss, than did patients with periodontal disease only [162]. Women who had experienced osteoporotic fractures also seemed to have an increased risk of loss of periodontal attachment [162].

One study compared the severity of periodontitis in postmenopausal women whose Fracture Risk Assessment Tool (FRAX) scores indicated a major risk for osteoporotic fracture versus controls [163]. Selection criteria for participants included: age 51 to 80 years; menopause for more than 1 year but less than 10 years; nonsmoker; hemoglobin A1c less than 7; and no pharmacologic treatment for osteoporosis within 5 years. FRAX scores were calculated and the participants were divided into two groups. Group 1 included 90 women with FRAX scores >20% (indicating major osteoporotic fracture risk); group 2 included 98 controls. The women in group 1 had significantly more severe periodontitis endpoints (e.g., clinical attachment loss, alveolar bone height, tooth loss) than controls. Plaque scores and bleeding on probe did not differ between the two groups [163].

The use of HRT appears to decrease the incidence of tooth loss in older women. In the Nurses' Health Study, which evaluated more than 42,000 postmenopausal women prospectively, the risk of tooth loss was lower in women taking HRT, after controlling for age and smoking [164]. A study of women in a California retirement community found that after adjusting for age, the use of estrogen replacement significantly decreased tooth loss and rates of edentia by 36%; the proportion of women with edentia declined with lengthier use of HRT [165].

Bisphosphonate drugs, such as alendronate, may retard the progression of alveolar bone loss associated with periodontitis. In one double-blind, placebo-controlled clinical study, alendronate lowered the risk of progressive loss of alveolar bone loss; during the nine-month trial, the relative risk of the loss of bone height and density was reduced to 0.45 in the alendronate group [166]. A study from 2019 found no improvement in maintaining alveolar bone level with the use of bisphosphonates but did suggest that its use may be promising as an adjunctive local delivery medication for management of periodontal diseases [167]. Two other studies support the assertion that bisphosphonates may be useful for periodontal treatment; however, existing information on this potential is limited [168,169,170]. However, bisphosphonate drugs are known to cause medication-related osteonecrosis of the jaw (MRONJ) in some patients, particularly those who underwent IV bisphosphonate therapy, who were taking bisphosphonates for extended periods of time, and/or who underwent dental procedures while taking bisphosphonate drugs [171,172].

According to the Bone Health and Osteoporosis Foundation (formerly the National Osteoporosis Foundation), an estimated 12.3 million Americans have osteoporosis and an additional 43.4 million have low bone density [173]. The 2 million new cases of osteoporotic fracture each year exceeds the annual number of new cases of myocardial infarction, breast, cancer, and prostate cancer combined. Annual fracture incidence is expected to increase 68%, to 3.2 million, by 2040 [173]. Diagnosis of this disease in an aging population is challenging, even though impressive progress has been made. Bone densitometry is the procedure that measures bone mineral density. Dual-energy x-ray absorptiometry (DEXA or DXA) has become the routine method for bone density measurement. It is very precise and has the advantage over other, older diagnostic methods of a much shortened examination time (i.e., 2 minutes versus 20 to 40 minutes) [174]. DEXA is of particular advantage in measuring the lumbar spine and proximal femur areas and has become the gold standard for bone densitometry [173].

Various drug therapies exist for osteoporosis, and research findings suggest the possibility of newer treatments on the horizon. One of the most commonly prescribed drugs for women with osteoporosis is alendronate sodium, a bone resorption inhibitor. Alendronate has proven effectiveness in preserving bone tissue and decreasing bone loss. Calcitonin is a bone metabolism regulator that slows the rate of bone turnover and seems to increase normal bone formation. It is indicated for the treatment of osteoporosis in women: who have been postmenopausal for at least five years; who have low bone density; who refuse or cannot tolerate estrogens; or in women for whom estrogens are contraindicated. It has not been recommended as a first-line treatment [175]. Calcitonin decreases bone resorption by inhibiting the activity of osteoclasts. Increases in bone mass of 1.5% to 13% have been reported, with the best responses noted in individuals with the highest bone turnover [176,177].

In 2011, the FDA approved denosumab for treatment of osteoporosis in postmenopausal women who are at high risk of fracture [177,178,179]. Denosumab acts by binding to and inhibiting receptor activator of nuclear factor kappaB ligand (RANKL). RANKL controls the differentiation, proliferation, and survival of osteoclasts. Inhibition of RANKL provides a lengthened period of absorption and inhibition of bone resorption [177,180].

In 2019, the FDA approved romosozumab for the treatment of osteoporosis in postmenopausal women who are at high risk of fracture. Romosozumab is a monoclonal antibody that inhibits sclerostin and improves bone mineral density [177,181].

Because most postmenopausal women have some degree of osteoporosis, they should take steps to prevent further bone loss. The best preventive measures are early education to encourage positive lifestyle habits before the disorder develops (ideally, well before menopause). The following methods have been identified as being helpful to prevent bone loss [158,173,182,183]:

Dairy products provide approximately 75% of the calcium in the average American's diet. However, the average daily calcium intake for women from dietary sources is only about half of the recommended amount. Women should be advised that it takes only three 10-ounce glasses of milk to supply 1,000 mg of calcium. Those who require more dietary calcium may choose to take supplements.

CHD signs and symptoms differ significantly between men and women. Women tend to have angina pectoris as the first symptom of heart disease; men initially have a myocardial infarction. Women rarely experience myocardial infarction as the initial manifestation of heart disease [85,188]. Diagnosis of coronary disease in women is difficult. Women may have unspecified, misleading pain, which often results in a search for other causes. In the past, women have not been included in major cardiovascular research and treatment. This has greatly compromised the discovery of facts concerning the early identification and treatment of heart disease in women and is only now being rectified.

Women may have combinations of negative social, psychologic, cultural, physical, and addictive behaviors that increase their CHD risk. The major modifiable risk factors are cigarette smoking, high blood cholesterol, high blood pressure, diabetes, physical inactivity, excessive alcohol consumption, stress, and excessive weight gain. Women who smoke and also have high blood pressure and high blood cholesterol levels are eight times more likely to develop heart disease than those who do not. Women who have diabetes are four to six times more likely to die from CHD than women without diabetes [85].

Dental health professionals should make sure patients understand that heart disease is not an inevitable consequence of aging; rather, it is a disease process that can be greatly influenced by lifestyle modification. Factors such as diet, exercise, not smoking, maintaining normal weight, monitoring blood pressure and cholesterol, and taking HRT (when appropriate) are all beneficial health behaviors.

There is some evidence linking poor dental health with heart disease, particularly in studies that have shown a link between periodontitis and CHD. For example, a study by Helsinki University Central Hospital evaluated 100 patients with acute myocardial infarctions and 102 controls and graded their dental health. The researchers found that dental health was significantly worse in the patients who had experienced a heart attack, compared to the controls, even after adjusting for factors such as age, socioeconomic class, cholesterol (total, HDL) and triglyceride levels, C-peptide levels, diabetes mellitus, and smoking [189]. A separate study by the same researchers in Finland concluded that dental infections were associated with the pathogenesis of atherosclerosis, which is the only characteristic other than traditional coronary risk factors that showed an independent association [190]. Subsequent studies have confirmed an association between chronic oral infections and slightly increased risk of myocardial infarction [191,192,193,194,195].

The National Health and Nutrition Examination Study (NHANES I) evaluated more than 9,000 people for a median of 14 years and found that individuals with periodontitis had a 25% greater likelihood of developing CHD (an association found to be statistically significant). Poor dental hygiene characterized by extensive dental debris and calculus also increased the risk of CAD [196]. A 2021 literature review found that the prevalence of heart disease is more common among individuals with periodontitis [197]. A systematic review published in 2022 concluded that periodontal disease may be an important nontraditional risk factor for acute coronary syndrome [198].

One hypothesis explaining the possible mechanism responsible for the link between CVD and periodontitis centers on bacterial products, such as lipopolysaccharides (LPS), that can enter the bloodstream and affect the cardiovascular system. Several studies have reported the presence of periodontal bacteria in cardiovascular specimens [199]. It has also been postulated that micro-organisms normally present in the oral cavity, including P. gingivalis and Streptococcus sanguis, enter the bloodstream through local action that induce bacteremias, grow within the vascular plaques, and have the potential to induce platelet aggregation [200]. A study of carotid atheromas using polymerase chain reaction found that 42% of atheromas contained at least one of the periodontal micro-organisms studied and 72% contained the bacterial DNA of one of these micro-organisms [201]. Although periodontal treatment as a means to prevent CVD is not recommended, the emergence of periodontal infection as a risk factor for CVD should lead dental and healthcare professionals to recognize that patients cannot be healthy without good oral health [14,202].

Gonorrhea, which is caused by the bacteria Neisseria gonorrhoeae, was once the most prevalent STI in the United States. Gonorrhea is one of the most common infectious diseases, with an estimated 677,769 persons in the United States acquiring the disease in 2021, an increase of 45% from 2016 [203]. After a decline in the incidence of the disease from 1975 to 1997, the national rate for gonorrhea has been steadily increasing. This STI is transmitted vaginally, orally, or anally by sexual activity or from the mother to newborn during delivery. The majority of women are asymptomatic early in the disease. When symptoms do occur, they may include burning on urination and increased vaginal discharge. In the oral cavity, the disease manifests as a stomatitis and may exhibit a clinical appearance similar to the oral lesions of erythema multiforme, erosive lichen planus, or herpetic stomatitis [203,204].

If the infection is in the oral cavity, diagnosis is made via bacteriologic evaluation of smears of the oral lesions. For infections in the genital area, gonorrhea is diagnosed in women with a culture of the cervical area. Both sexual partners should be tested and treated if either has a positive test for gonorrhea. Patients infected with gonorrhea are often co-infected with chlamydia and routinely treated with a regimen effective against both organisms. The recommended treatment of uncomplicated urogenital, anorectal, and pharyngeal N. gonorrhoeae infection in the United States is single-dose ceftriaxone 500 mg IM for persons weighing <150 kg. Administer 1 g ceftriaxone for persons weighing ≥150 kg [205]. If ceftriaxone is unavailable, administer either gentamicin 240 mg IM in a single dose, or azithromycin 2 g orally in a single dose, or cefixime 800 mg orally in a single dose [205]. Women should be informed of the need for retesting to verify eradication of the infection.

Syphilis is a bacterial STI caused by the spirochete Treponema pallidum. Like gonorrhea, syphilis is transmitted vaginally, orally, or anally through sexual activity, and via maternofetal transmission. In some cases, the disease has been acquired by dentists and hygienists providing dental treatment for a patient with syphilis during a contagious stage of the disease. Universal precautions apply, with the routine use of gloves, mask, and eye protection. Although syphilis is not as widespread as gonorrhea, its incidence is on the rise, which is especially ominous because of the harmful effects the untreated bacterium has on the heart, eyes, and central nervous system [203]. An estimated 133,945 cases of syphilis were reported in 2021, up 52% from 2016 [203].

In the first stage of syphilis, a painless, ulcerlike lesion called a chancre appears at the site of the infection, which may include the oral cavity and lips, on average about three weeks after contact with the infectious agent. On the lips, the chancre is often crusted and brownish, while intraoral lesions tend to be covered by a grayish, white membrane [204]. The chancre disappears within a few weeks, but if the syphilis is untreated, the bacteria continue to proliferate within the body. The untreated syphilis may progress through secondary and tertiary stages. During the secondary stage, there can be multiple oral lesions manifesting as painless, grayish-white plaques, most often found on the gingival, tongue, or buccal mucosa. They may have an irregular shape and are extremely contagious. These secondary signs and symptoms will resolve, with or without treatment; however, without treatment, the infection will progress. The tertiary lesions may not develop for a number of years, most frequently affecting the cardiovascular and central nervous systems. In the mouth, tertiary lesions are far more commonly observed than the primary or secondary lesions and are most often manifested by an interstitial or atrophic glossitis. There is a reported predilection for this luetic glossitis to undergo transformation to carcinoma [203,204].

Darkfield examinations and molecular tests for detecting T. pallidum directly from lesion exudate or tissue are the definitive methods for diagnosing early syphilis and congenital syphilis [205]. Treatment includes antibiotics such as penicillin, doxycycline, tetracycline, or azithromycin. The preferred treatment for patients not allergic to penicillin is a single dose of penicillin G at 2.4 million units IM for adults and 50,000 units/kg body weight IM for infants and children [205]. Although syphilis can also be transmitted from an infected mother to her fetus (so-called congenital or prenatal syphilis), this form of the infection is very uncommon today due to routine blood tests conducted as part of prenatal care. In these cases, lesions may occur in any region of the oral cavity and tend to have a pink or red color [204].

Herpes is typically manifested either as a genital or oral viral infection. When it begins in the genital area, the infecting agent has historically been identified as HSV-2, but an increasing proportion of infections have been attributed to herpes simplex virus type 1 (HSV-1) [205]. Most infections are transmitted by persons unaware that they have the infection or who are asymptomatic when transmission occurs [205]. Similar to other STIs, HSV may be transmitted vaginally, orally, or anally through sexual activity and to a newborn during delivery. Herpes is most contagious during active outbreaks of the disease when lesions are present, but cells may be shed at other times. Latex condoms used during genital or oral sex are effective barriers to HSV [203]. Herpes is also commonly spread through kissing, using the same eating utensils, or sharing personal items with an individual infected with the herpes virus ("cold sores"). Parents, or other relatives, frequently infect their children in these ways, not knowing that "cold sores" are manifestations of the herpes virus.

HSV-1 is often found in the oral cavity and presents with signs and symptoms similar to HSV-2. A herpetic infection can be designated as primary in individuals not previously exposed, who have not yet developed antibodies to the virus, or recurrent in patients with previous exposure who have antibodies present. The primary infection often presents as a generalized stomatitis. Individual and discreet lesions typically appear after a prodromal sensation reported by many patients six to eight days after infection. Papules appear and develop into blisters that may become extremely painful ulcers. Although the clinical manifestation may heal and disappear, the virus is still present in the patient, often at a location remote to where the lesions occur [203]. Recurring outbreaks may be related to stress, hormonal changes, trauma, exposure to ultraviolet sunlight, or fatigue. Management of HSV should address the chronic nature of the infection rather than focusing solely on treating acute episodes of genital lesions [205].

Diagnosis of HSV-1 and HSV-2 can be difficult because the lesions classically associated with HSV are absent in many infected persons at the time of clinical evaluation [205]. Diagnosis is made by clinical inspection and culture of the sores. Prognosis and counseling depend on which HSV type is present. Type-specific serologic tests can be used to aid in the diagnosis of HSV infection in the absence of genital lesions [205]. Herpes does not have a cure, but antiviral drugs such as acyclovir, (Zovirax), famciclovir (Famvir), and valacyclovir (Valtrex) can help relieve pain, speed healing, and possibly decrease the incidence of outbreaks [21,24,177,205].

An infection with Chlamydia trachomatis is the most common bacterial STI in the United States (with 1.6 million cases in 2020) [21,85,102,203,206]. Although many infected women are asymptomatic, any one of the following symptoms may occur one to three weeks after contact: frequent, uncomfortable urination; dyspareunia; cervicitis with scant cervical discharge; lower abdominal pain; and/or pelvic inflammatory disease (PID) [21]. The recommended treatment is doxycycline 100 mg orally twice daily for seven days. Alternative regimens include azithromycin 1 g orally in a single dose or levofloxacin 500 mg orally once daily for seven days [21,177,205]. Pregnant women should be treated with azithromycin or amoxicillin, as the members of the tetracycline family (e.g., doxycycline hyclate) should be avoided during the time of fetal tooth development due to the well-known possibility of permanent staining of the teeth.

Human papillomavirus (HPV) causes condyloma (i.e., genital warts). It is the most common viral STI and is highly prevalent among young, sexually active individuals. HPV is transmitted by skin-to-skin contact rather than via the exchange of bodily fluids [207]. More than 150 types of HPV have been identified, and more than 40 can infect the male and female genital tract [205]. High-risk HPV identified in genital cancers include types 6, 18, 45, and 58 [86]. A substantial proportion of cancers and anogenital warts are attributable to HPV in the United States. An estimated 34,800 new HPV-attributable cancers occurred every year during 2012–2016. Before the introduction of HPV vaccines, approximately 355,000 new cases of anogenital warts occurred every year [205].

Women are more susceptible to HPV infection than men because cells in the cervix divide swiftly, facilitating the spread of the virus. Most HPV infection is not visible to the naked eye, but genital warts that appear as small bumps or groups of bumps in the genital area are the most common recognized visible manifestation [86]. Diagnosis is made by inspection, colposcopy, biopsy, or cytology. There is no treatment for the virus, but there are treatments for the diseases that HPV can cause. Patient-applied and provider-applied treatments are available. Factors affecting the choice of treatment include wart size, number, location, morphology, cost, and convenience. Imiquimod 5% cream is used in the treatment of external genital warts. Cryotherapy with liquid nitrogen may also be used in treatment [86,203,205]. HPV is preventable by adopting safer sexual practices; women should limit the number of partners and use latex condoms. In addition, it is recommended that all girls and boys 11 to 26 years of age who have not completed the vaccine series receive the HPV vaccine [203,205].

HIV is the virus that causes acquired immunodeficiency syndrome (AIDS). Safer sexual practices to prevent HIV include limiting the number of partners, avoiding unprotected anal intercourse, and avoiding contact with the blood, semen, or vaginal secretions of others, including via the oral route. Women with HIV infection may experience remissions with medication regimens and improved supportive therapy that make it possible to regain high concentrations of T4/CD4 cells. However, some emerging HIV strains have proven to be resistant to current drug therapies [208].

Kaposi sarcoma, a malignancy that may affect the skin or oral cavity, is a common complication of late-stage AIDS. Oral lesions associated with Kaposi sarcoma most commonly appear on the palate but may manifest anywhere in the mouth [25].