Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
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We wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
IntechOpen is proud to announce that 191 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\n
Throughout the years, the list has named a total of 261 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\n
Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\n
We wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
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1. Introduction
Colposcopy of the vulva—vulvoscopy—is an essential step in gynecology examination. However, it is not as systematic as colposcopic of the cervix examination due to the normal histology as this area and the multifocal nature of vulvar intraepithelial disease makes the examination more difficult and less objective than the cervix examination.
In this chapter, we will focus on the non‐neoplastic disorders of vulvar skin disorders that we could usually find in a routine gynecology examination. Neoplastic vulvar disorders should need revised review in another chapter.
2. Tissue basis of colposcopy of the vulva
Presently, acetic acid is universally used as an adjunct to colposcopic examination [1]..As a tool for examination of the cervix and vagina, colposcopy is based on the variable absorption and reflection of white light off different tissue interfaces [2]. Mucosal tissue color depends on the amount of hemoglobin viewed at the tissue surface, which gives the tissue different degrees of redness. The degree of redness depends on the distance between the underlying vasculature and the surface, which indirectly implies the amount of cellular material (stroma and epithelium) between the vessels and surface.
How acetic acid works as a contrast agent is unclear. Although acetic acid can improve the surface light reflection by dissolving mucus, it can also modify cellular proteins, including cytokeratins and nuclear proteins. Lastly, it is believed (but not yet proved) that acetic acid dehydrates the cell, which removes most of the cytoplasm. After dehydration, the cell is left with organelles, cytoskeleton filaments, and nuclear proteins. The effects of acetic acid are transitory: when rehydration of the cell cytoplasm occurs, any protein alterations revert to their normal state [3].
Because acetic acid specifically modifies cell cytoplasm and nuclear proteins, the contrast created by its application to the cervical and vaginal mucosa depends on the number of surface epithelial cells, the amount of cytoplasm in these cells, and the amount of nuclear material in each cell. It would follow that more light would be absorbed and little light would be reflected if there were few surface cells with small nuclei and large amounts of cytoplasm. The effects of acetic acid on these cells would require frequent reapplications to maintain the dehydrated state. The opposite (more light reflection) would occur if the surface interface were to consist of numerous cells with large nuclei and small amounts of cytoplasm. The effects of acetic acid would last longer because these cells would have little cytoplasmic fluid to rehydrate.
Thickness of the skin affects the opacity, and it varies from different areas of the vulva. Skin of hair‐bearing areas is thicker than the skin of other areas of the vulva. This is why histologically identical lesions may have different appearance when present on different parts of the vulva. Its prominent surface keratin layer does not provide a clear view of the underlying blood vessels. Pigmentation can also obscure blood vessels. Therefore, vascular patterns are less marked and less reliable than with colposcopy of the cervix. Vascular aberrations such as punctuations and mosaic patterns do not easily develop on vulvar skin. They are less common and can be practically seen only on the non‐hearing areas. Thus, leucoplasia and acetowhite epithelium are the most frequent colposcopical manifestations of vulvar pathology.
3. Technique of vulvoscopy
3.1. Inspection
The clinical examination of the vulva should form part of the routine gynecological examination, thus enabling both the correct diagnosis and treatment of numerous alterations and the prevention and early diagnosis of vulvar intraepithelial neoplasia (VIN) and invasive neoplasias. A correct evaluation should include basic anamnestic data, a list of symptoms localized in the vulva region, and a careful inspection and palpation. The vulva should be examined in a systematic fashion to include the mons pubis and labia majora, the labia minora, clitoral prepuce, clitoris, perineum, and anal areas. Attention should be given in the examination of the vestibule to the hymeneal ring or remnants, to the gland openings (Bartholin’s and Skene’s), and to the urinary meatus.
The successive aim is to identify the main clinical aspects of the lesion which can be summarized as changes of color, presence of swellings on surface, and loss of substance. The critical evaluation of lesions should allow critical evaluation of lesions and also allow the gynecologist to formulate a diagnosis to propose to the pathologist. In this way, the collaboration between clinician and pathologist can contribute to progress in the diagnosis and treatment of vulvar diseases.
3.2. Application of acetic acid
It should be performed after applying 3–5% acetic acid to the vulva for several minutes using soaked gauze pads. Keratinization requires longer acetic acid application for effect and often renders typical colposcopic grading criteria useless. Colposcopy should begin by using the lowest magnification (6×) to quickly scan the vulva. Later, it can be proceeded to higher magnifications, as necessary, to examine smaller satellite lesions.
Acetic acid can cause acetowhitening of normal skin at the vestibule, normal variant of skin at the vestibule, and the normal variant of vestibular papillomatosis, which can limit its usefulness in practice. Any inflammatory condition of the vulva, including infection and trauma from intercourse, can cause acetowhitening (Figure 1).
Figure 1.
Normal acetowhitening of the vulvar skin.
3.3. Collins test
The test that uses a solution of toluidine blue to mark vulvar lesions is known as the Colling test. All foci of nuclear activity will keep the color and become stained. This may happen not only in neoplasias but also in the presence of ulcerations, lacetations, peparative changes, and parakeratosis. Historically, toluidine blue and Lugol’s iodine solutions were used to stain the vulva and aid in identifying abnormal areas, but this practice has largely fallen out of favor because of high false‐positive and false‐negative rates [5].
3.4. Biopsy
Vulvoscopy can localize the lesion exactly. It usually cannot predict the histological nature of the lesion. Biopsy is indicated for visible lesions for which definitive diagnosis cannot be made on clinical grounds, possible malignancy, visible lesions with presumed clinical diagnosis that is not responding to usual therapy, lesions with atypical vascular patterns, or stable lesions that rapidly change in color, border, or size. Expert opinion is divided regarding the need for biopsy of all warty lesions, but biopsy should be performed in postmenopausal women with apparent genital warts and in women of all ages with suspected condyloma in whom topical therapies have failed.
Although information regarding the evaluation of women with immunocompromised conditions and human papilloma virus (HPV)‐related disease is limited, human immunodeficiency virus (HIV)‐seropositive patients and patients on immunosuppression after organ transplant may need biopsy of lesions when the level of suspicion is lower [6].
The area to be biopsied should be infiltrated with 1–2% lidocaine using a fine‐gauge needle [7]. Epinephrine with the lidocaine can help with hemostasis but can make the injection burn.
After a test to ensure adequate anesthetic effect using fine‐tipped forceps, a biopsy can be obtained using a cervical biopsy forceps, a keys punch 3–5 mm, or a small scalpel blade, depending on the size and nature of the lesion. Small biopsy sites can be treated with Monsel’s solution or silver nitrate to achieve hemostasis. Only rarely absorbable sutures are needed. Location of biopsies should be indicated on a vulvar diagram or photograph, and multiple biopsies should be sent separately for pathologic evaluation (Figures 2 and 3).
Figure 2.
Vulvar biopsy with cervical forceps.
Figure 3.
Vulvar biopsy with keys punch.
The simplest method is biopsy with cervical biopsy forceps, but an attempt should be made to get a specimen, at least 5 mm thick. Ulcerative lesions and very thick lesions should be completely excised to rule out focal invasion (excision biopsy).
The etiology and clinical significance of vulvar vestibular papillomatosis (VVP) are still controversial; in the past, it was considered to be a result of human papilloma virus (HPV) infection, but actually, there are many studies that show only a rare relationship between VVP and HPV. Currently, VVP is considered as an anatomical variant of the vulva [8].
VVP was first recognized in 1981. A few years later, in 1991, the report by the International Society for the Study of Vulvar Diseases (ISSVD) described papillomatosis of the vulvar vestibule as the presence of multiple papillae that may cover the mucosal surface of the labia minora. Since then, VVP has been reported under a variety of names: vestibular papillae, hirsutoid papillomas of vulvae, vulvar squamous papillomatosis, micropapillomatosis labialis, and many others [8]. VVP has been seen with HPV infection, but a consistent association has not been proven. Therefore, most recent studies consider VVP as a normal variant in the vulvar vestibule architecture, not directly related to infection by HPV [9]. It is likely that this finding is a female counterpart of male pearly penile papules [10] (Figure 4).
Figure 4.
Vestibular papillomatosis.
Vestibular papillomatosis has been recorded in healthy young women in the range of 1–33%. The papillae of 1–2 mm diameter have the same color as the adjacent mucosa. The lesions are soft and are symmetrical or may be linear. They may cover labia minora and the introitus vaginae to a variable extent. They may resemble warts but are distinguished by the fact that the bases of individual papules remain separate unlike in warts where filiform projections tend to fuse at the base and lesions are not confined to the vestibule or the inner aspects of labia minora. In addition, application of 5% acetic acid causes whitening of the lesions in warts, whereas vestibular papillae remain unchanged.
5. Vulvar infections
Vulvar infections can be of variable location and multiple etiologies. Infections of the lower genital tract may be both specific and nonspecific, and affect the vulva more or less intensely. Some vulvar infections begin in the vulva and others in the vagina or nearby organs [11].
The external organs of the vulva include the labia majora and minora (folds of skin), the clitoris, and the vestibular glands. The basic symptoms of vulvitis are superficial red, swollen, and moisture‐laden lesions on the skin of the vulva.
The characteristic symptoms are erythema, edema, pruritus, excoriation, and ulcers.
During vulvoscopy, color changes, topography, surface contour, and angioarchitecture of all parts of vulva should be noted. There are some vulvoscopic images characteristic of vulvar infections.
In skin, areas acetowhite and raised on skin, or areas with high yellow‐white spots. If there is a predominance of reddish lesions, we may suspect infection by candida, dermatofitides, syphilis, erysipelas, or simply subcutaneous cellulitis.
In the mucosa, the infections produce an image of the mucosa acetoblanca and without being elevated.
We can visualize in the whole vulva injuries of the type of fissures, erosions, and ulcers of different characteristics.
The presence of tumors of infectious component makes one think of infection in sweat glands, sebaceous glands of the vulva or even in follicles, or Bartholin’s glands.
6. Bacterial infections
6.1. Folliculitis
Local infection of the hair follicle of vulvar hair by germs of the type Staphylococcus aureus or Streptococcus. This can happen because of shaving, waxing, or even friction.
It is described as an inflammation of the skin surrounding the follicle and erythema with elevation, small painful erythematous plaques, or palpation with punctate pustule. The treatment is usually local topical antibiotic, and in cases of increased dissemination systemic antibiotic treatment, penicillin derivatives such as clavulanic amoxicillin or minocycline and in topical treatment mupirocin.
6.2. Cellulitis
Infection of the subcutaneous cellular connective tissues was found below the skin in the vulvar area, and with easy extension to other areas through the subcutaneous tissue. The entrance of the bacteria can be from a wound or erosion or a frequent boil on the vulva.
It is described as an erythematous zone, warm and with a slight edema that affects the subcutaneous tissue.
The most frequent germs in cellulitis are Staphylococcus and Streptococcus. Group A strep (Streptococcus) bacteria are the most common cause. The bacteria enter your body when you get an injury such as a bruise, burn, surgical cut, or wound.
Their treatment must be with systemic antibiotic, clavulanic amoxicillin, or ampicillin (Figure 5).
Figure 5.
Vulvar cellulitis.
6.3. Necrotizing fasciitis
It is a severe acute bacterial infection that spreads tissue through subcutaneous cells and fascia resulting in tissue necrosis. One‐third of patients end up in septic shock with multiorgan failure. Treatment should be rapid with hemodynamic support, extensive surgical treatment, and systemic antibiotic therapy.
In the case of the vulvar region may be associated secondarily to surgical processes, such as partial vulvectomies, episiotomies of labor, or vulvar tears due to trauma.
6.4. Hidradenitis suppurativa
Hidradenitis suppurativa (HS) [12] is an uncommon skin condition that affects the vulva and other parts of the skin. The pimple‐like bumps tend to develop in places where everyday pimples do not appear. Chronic inflammatory diseases of apocrine sebaceous glands are subsequently infected by bacteria such as Proteus, Escherichia coli, Klebsiella, Pseudomonas, Streptococcus, or Staphylococcus.
Initially, they are subcutaneous nodules that evolve occasionally to the formation of abscess due to bacterial superinfection and rupture. It can affect the skin of the vulvar region and fistulize later.
Early diagnosis and treatment can prevent HS from worsening. Early and long‐term treatment may help control pain, promote wound healing, keep new lumps from forming, and prevent complications. The treatment is surgical with drainage and associated antibiotic treatment, sometimes systemic, depending on the dissemination and severity of infection (Figure 6).
Figure 6.
Pimple‐like bumps in hidradenitis suppurativa.
7. Bartholin’s abscess
The Bartholin glands are located under the skin on either side of the opening of the vagina. It is an infectious process secondary to the obstruction of the duct of the Bartholin’s gland that favors bacterial overinfection. Generally, the germs that produce the infection are mixed bacterial flora.
Clinically, it manifests as a tumor, with pain, blushing, and local heat.
Generally, in the acute process with surgical drainage with marsupialization of the gland or spontaneous drainage is sufficient associated with the use of oral antibiotics (cephalosporins, amoxicillin, and doxycycline).
7.1. Syphilis
It is a sexually transmitted infection caused by the mildly contagious Treponema pallidum.
The initial lesion is called primary syphilis. It is defined as the primary chancre being the inoculation site of the treponema, and after a macula appear initial papules that end in an indurated and painless ulcer, this ulcer is usually accompanied by an inguinal adenopathy. This lesion is called chancre and is defined as a firm, painless, and non‐irritating skin ulcer, but there may be multiple sores. The initial lesion may appear on the vulva, vagina, or cervix. It can be kept up to 2–8 weeks and then cure spontaneously.
Secondary syphilis can manifest at 6 weeks or 6 months later by hematopoietic dissemination of the treponema. At this time, the characteristic lesions of the vulva are flat condylomas and erosive macular exanthema (Figure 7).
Figure 7.
Syphilis lesions.
Tertiary syphilis occurs in cases that have not been treated. After a few years after the first infection, it is characterized because it has no characteristic vulvar lesions.
The diagnosis of primary and secondary syphilis can be performed with a microscopic examination in dark background, in which the spirochete can be visualized, and another diagnostic method is the serological tests, although these become positive in the late primary phase (VDRL and RPR or specific TPPA and FTA‐ABS).
The treatment in any stage is with benzathine penicillin G injected into a muscle 2.4 million. In tertiary syphilis, we should use benzathine penicillin G intravenous.
7.2. Chancroid
Sexually transmitted disease is caused by Haemophilus ducreyi. H. ducreyi is a fastidious gram‐negative coccobacillus bacteria frequent in the third world.
After a period of incubation of 5–7 days, lesions develop in the vulvar area, clitoris, or lips. With multiple painful papules surrounded by erythema, these lesions end up overinfecting and end up ulcerating. The chancre is soft superficial and surrounded inflammatory erythema with necrotic background. Not all patients are presented with this chancre, one‐third presents multiple ulcerations that tend to unite and are accompanied by the presence of inflammatory and painful inguinal adenopathy.
The diagnosis is made by staining gram. H. ducreyi can be cultured on chocolate agar. The treatment is a single dose of azithromycin or ceftriaxone.
7.3. Lymphogranuloma venereum
Lymphogranuloma venereum is an uncommon sexually transmitted disease caused by Chlamydia trachomatis. The lymphogranuloma venereum is endemic in certain areas of Africa, Southeast Asia, India, the Caribbean, and South America. It is rare in industrialized countries.
It is characterized by a painless ulcerated lesion in the vulvar or vulva fork, which at 15 days is associated with multiple and acute regional lymphadenitis. In vulvar lesions, the most affected nodes are the obturators.
Diagnosis is by culture or arrest of antibodies.
The treatment is oral doxycycline or erythromycin.
8. Fungus infection
8.1. Candidiasis
It is the most frequent vulvar infection and is usually associated with vulvovaginitis. Produced by candida fungus, saprophytic fungus is usually found in the genital and intestinal tract.
In our environment, the most frequent is Candida albicans and is estimated to produce 90% of vulvovaginal infections. Other less frequent but more resistant to treatment candida may be Candida krusei, Candida glabrata, or Candida tropicalis.
The clinic is variable and more in vulvar involvement, it may be asymptomatic, or produce pruritus attempt with erythema and vulvar edema. If accompanied by vaginitis, there will also be whitish leucorrhoea. In advanced cases, we can see papules and pustules with ulcerations and fissures.
Treatment is with local or systemic imidazoles. One should always think about discarding states of immunosuppression (Figure 8).
Figure 8.
Candida albicans vulvovaginal infection.
8.2. Dermatophytosis (Tinea infections)
Dermatophytosis (tinea) infections are fungal infections caused by dermatophytes—a group of fungi that invade and grow in dead keratin. Several species commonly invade human keratin, and these belong to the epidermophyton, microsporum, and trichophyton genera. They tend to grow outward on skin, producing a ring‐like pattern, which coined the term “ringworm.” The lesion is erythematous and itchy and extends through the folds and inner side of thighs, also called margin eczema of Hebra. The treatment is with antifungals agents, either topically or systemically (through the blood).
9. Parasites infection
9.1. Scabies
It is an infection produced by the Sarcoptes scabiei or the itching mite that is a parasitic arthropod that penetrates the skin and causes scabies. Lesions are considered to be a skin hypersensitivity reaction to the parasite.
The lesions are lines or grooves that have a small papule at the end. It is very pruriginous and is accompanied by scratching injuries. The diagnosis is made by visualizing the parasite in lesions.
The treatment is with 5% permethrin.
9.2. Pediculosis pubis
Pediculosis pubis is a human ectoparasitosis caused by Phthirus pubis, this is generally consider of sexual transmission and variable percentages is associated with other diseases of this kind.
It is an infection caused by lice, P. pubis, in vulvar hair. Pediculosis is a very contagious sexually transmitted disease. The parasite can survive up to 24 hours outside the host.
The primary clinic is pruritus, and as a consequence, the visible lesions are scratch lesions.
Diagnosis is the visualization of the insect or nits.
Treatment also was with 1% permethrin.
10. Virus infections
10.1. Molluscum contagiosum
It is an infection produced by a Poxvirus. The transmission is by direct contact and it is frequent in children. In adults, it can be considered sexually transmitted by contact. The lesion is characterized as a pink papular elevation, that then becomes more blaquecina, is accompanied by an erythematous halo, the lesion is very pruriginous and is usually umbilicated.
They are multiple and of small sizes.
The treatment is with surgical or medical curettage.
10.2. Herpes virus
A total of 80% of vulvar and genital herpes virus lesions are produced by HSV‐2 and estimated to be 15% HSV‐1. Its prevalence has been increasing in recent years. Transmission may be by direct contact with ulcerated lesions or by relation to an asymptomatic person.
Vulvar lesions are vesicles in a different location with ulcers and erythema around them, characterized by being very painful. If it affects the urethra, it can lead to dysuria.
The diagnosis is clinical and confirmed by viral culture. Treatment is with Acyclovir, guanosine analog, or famciclovir or valaciclovir (Figure 9).
Figure 9.
Vulvar herpes lesions are vesicles.
11. Human papilloma virus (HPV) infection
Papillomaviruses are a large and diverse group of viruses. It includes approximately 200 fully described types that have been detected in humans. Human papilloma viruses (HPV) are etiologic agents during various benign and malignant lesions of mucous membrane and skin epithelium. HPV is transmitted through contact with infected skin or mucosa. Very importantly, persistent HPV infection of certain types is a leading cause of carcinoma of uterine cervix, penis, vulva, vagina, anal canal, and fauces (including tongue base and tonsils). HPV infection prophylaxis is the best means to control HPV‐conditioned diseases, and vaccination, as had been demonstrated, is the most effective method of its prophylaxis (Table 1).
A. Clinical: evident without magnification or acetic acid
1. Acuminate
2. Papular
3. Pamilomatosus
B. Subclinical: better assessed by magnification and acetic acid
1. Micropapillary
2. Flat
C. Non‐clinical: evident by laboratory techniques
Table 1.
Human papillomavirus (HPV) nomenclature.
HPV types are divided into low‐risk and high‐risk types based upon associated risk for cancer. The low‐risk types HPV 6 and/or HPV 11 are detected in around 90% of anogenital warts, although coinfection with other low‐risk or high‐risk types of HPV is common.
Principle characteristics and clinical manifestations of papillomavirus infection are examined as follows:
11.1. Clinical HPV infection
HPV infection is the most common sexually transmitted disease in the world. At least 75% of sexually active adults in the USA have been infected with at least one genital HPV type at some time [13]. The estimated prevalence rate of HPV anogenital infection in the US adult population is 10–20% among unvaccinated individuals. HPV infection rates are trending downward in countries where HPV vaccination has been implemented.
Condylomata are relatively common. Reported prevalence rates based upon reviews of administrative databases or medical charts and prospective physician reports ranged from 0.13 to 0.56%, and reported prevalence rates based upon genital examinations ranged from 0.2 to 5.1%. Condylomata acuminate (CA) is the most common in young adults [15].
Sexual activity is the primary risk factor for anogenital human papillomavirus (HPV) infection. Once acquired, HPV infection can enter a latent phase without signs or symptoms.
However, only a small proportion of patients infected by this virus will express the disease. Nevertheless, this dermatitis remains one of the most prevalent of sexually transmitted diseases and poses problems in its management. These problems are centered on phenomena of viral latency, which do not permit one to guarantee the cure of the patient, and the absence of specific anti‐viral treatment.
Immunosuppression is associated with the development of larger and more treatment‐resistant condylomata, higher rates of recurrence, and malignant transformation of anogenital warts. As examples, condylomata in patients with human immunodeficiency virus (HIV) infection, receiving immunosuppressive therapy, or with diabetes [16] can be challenging to treat. Extensive anogenital warts have been reported in patients with human T‐lymphotropic virus type I (HTLV‐I) infection, and in association with the immune reconstitution inflammatory syndrome [14, 17].
Smoking has been associated with increased risk for condylomata. Risk for condylomata may increase as the number of cigarettes smoked per day and number of pack‐years increase.
Male circumcision may reduce risk for HPV infection.
HPV may infect any part of the vulva, but initial changes most often appear on the areas traumatized during sexual intercourse. External anogenital warts are typically found on the vulva and groin. They often extend to the lower vagina, and sometimes the entire vagina is affected. Posteriorly infection might extend to the perineum, perianal skin, and/or suprapubic skin. During the examination, acetic acid is applied and the field is colposcopically examined.
11.1.1. Condyloma acuminata
Although human papillomavirus (HPV) 6 and HPV 11, low‐risk HPV types, are responsible for most cases of CA, coinfection with high‐risk HPV genotypes linked to anogenital and head and neck cancers is common.
In patients who develop CA, the usual incubation period is three weeks to eight months.
In most cases, clinicians familiar with the clinical manifestations of CA can diagnose CA based upon the physical examination. Findings that suggest CA are single or multiple soft, smooth, or papillated papules or plaques are limited to the anogenital area. The color varies: warts may be white, skin‐colored, erythematous (pink or red), violaceous, brown, or hyperpigmented. Anogenital warts are usually soft to palpation and can range from 1 mm to more than several centimeters in diameter. The warts are typically asymptomatic but may be pruritic.
Patients may have simultaneous infection of the genital area and perianal skin. Therefore, all areas of predilection for CA (vulva, penis, perineum, perianal skin, mons pubis, and crural folds) should be examined. Of note, uncircumcised foreskin or hair can obscure warts, warranting careful examination.
The physical examination should also include an assessment for other clinical signs that may suggest coexisting sexually transmitted diseases, such as ulcerations, adenopathy, vesicles, or discharge.
If there is uncertainty about the diagnosis, a biopsy should be performed. A shave procedure to remove a suspected wart or sample a large suspected wart is usually sufficient.
In addition, a biopsy to confirm the diagnosis and rule out malignancy is beneficial for CA that appear refractory to treatment, especially in immunosuppressed patients. Other indications for biopsy include atypical features (e.g., induration, fixation to underlying structures, bleeding, atypical pigmentation, or ulceration).
Human papillomavirus (HPV) testing of warts is not routinely indicated for diagnosis. Testing does not confirm the diagnosis and does not influence management of CA [18].
Application of acetic acid has a low positive predictive value for diagnosing external anogenital warts. Therefore, use cannot be advocated for diagnosis [19]. False‐positive results commonly occur, resulting from parakeratosis in other pathologic processes (e.g., psoriasis, candidiasis, healing epithelium, and lichen planus). The pain associated with acetic acid examination is another reason to avoid its use.
The evaluation of patients with CA should include a review of the need for testing for other sexually transmitted diseases and concomitant internal involvement.
Patients with external anogenital warts may have concomitant involvement of the urethra, vagina, cervix, or rectum.
Giant condyloma acuminatum is a rare tumor first described as Buschke‐Löwenstein tumor. The disease begins as an apparently straightforward viral wart, but relentlessly enlarges destruction to surrounding tissue. It is a low‐grade form of squamous cell carcinoma associated with HPV 6 and 11 that most commonly manifests on the glans penis, foreskin, and perianal regions. Giant condyloma acuminatum can manifest in large cauliflower shapes and can form fistulas and/or abscesses with local neoplastic invasion. Clinically, the tumor looks malignant, but in contrast to cancer, it does not metastasize. It tends to infiltrate underlying tissues and cause local destruction.
For women with limited vulvar disease who can comply with self‐therapy at home, we suggest imiquimod over podophyllotoxin as initial medical treatment. For those who cannot comply with self‐therapy or fail self‐therapy, we suggest treatment with trichloroacetic acid (TCA) rather than cryotherapy.
Laser ablation is our preferred surgical approach as it is possible to reach into the vagina and the depth of treatment can be controlled (Figure 10).
Figure 10.
Vulvar condylomata.
11.2. Subclinical infections
Subclinical infections may be visualized through the colposcope after the application of 3–5% acetic acid. They are associated with intraepithelial disease (VIN) in 10–20% of cases. These lesions are distributed around the vaginal introitus, on the perineum and perianal areas. They can be asymptomatic, but in many women, they can cause pruritus and dyspareunia. Vulvar inspeccion will be normal skin, and colposcopically subclinical HPV infection cannot be distinguished from VIN, making biopsy necessary. Conservative treatment is recommended (Figure 11 and Table 2).
Figure 11.
Acetowhite mosaic changes.
Feature
Low‐grade lesion
High‐grade lesions
Color
Snow white to bright white
Bright white to dull (oyster) gray
Lesion size and shape
Relatively large and geographic; raised and papillary
Relatively small; smooth and flat
Location
Throughout the ectocervix
In the upper transformation zone at or near the new squamocolumnar junction
Time interval to color change; number of reapplications
Slow to change; requires numerous reapplications to maintain color differential
Rapid change; requires few reapplications to maintain color differential
Border
Irregular; relatively indistinct
Straight, raised or rolled; prominent
Table 2.
Acetowhite changes in low‐ and high‐grade colposcopic lesions.
11.2.1. Vulvar trauma
The etiological factors that can damage the genital tract are multiple and varied and range from births, coitus, foreign bodies, thermal stimuli, chemical, accidents, surgical acts and in another dimension, injuries or caused by sexual aggression.
The most severe forms that significantly compromise the anatomy or physiology of the genitals.
The most frequent injuries are the direct ones and according to where they are located, we can speak of:
Hymen trauma: The hymen is a rudimentary membrane that is not very vascularized and can rupture with first relation or with the penetration of other objects such as tampons.
Vulvar tear: They can be secondary to sudden sexual intercourse or penetration of foreign bodies and usually have continuity with the vagina. Here, we could also describe the episiotomy or tear due to vaginal delivery.
Accident wounds are the most common vulvar trauma, as we have described before may be direct or indirect.
The direct ones are by falls, blows, or impalamientos with other objects. They are frequent in girls due to injuries with bicycles or blows when leaving the bath or pool.
The indirect ones we see them in great traffic accidents or collapses.
Treatment of injuries and injuries of the genital tract: It is designed to contain bleeding and plastic reconstruction of the injured organ if appropriate. The first will be done by ligating the bleeding vessels that are identified or by hemostatic points. The wound will be sutured with loose stitches. There will then be a plugging in the area of the wound.
In the case of bruises, most cases require drainage to prevent the hematoma from dissecting the adjacent tissues by the tension they generate.
In all injuries, it must be ruled out that there has been no injury to internal organs either directly or indirectly.
The most common vulvar trauma is that produced by labor, vulvovaginal tear that may require subsequent suturing (Figure 12).
Figure 12.
Vulvar trauma.
11.2.2. Liquen esclerosus (LS)
LS is a non‐neoplastic chronic lymphocyte‐mediated inflammatory dermatosis with distinctive dermal sclerosis and with a predilection for the anogenital skin in women. The true prevalence is not known.
It usually occurs in the anogenital region (85–98% of cases), but can develop on any skin surface. Extragenital lesions are present in up to 15% of patients, although this may be an underes. Vulvar LS can occur at any age but tends to have two peaks of onset: prepubertal girls and perimenopausal or postmenopausal women [4]. It is one of the most common conditions treated in vulvar clinics. The true prevalence is not known; estimates range from 1 in 30 older adult women to 1 in 59 women in a general gynecology practice to 1 in 300 to 1000 patients referred to dermatologists timate.
Pruritus and soreness or irritation are the most common symptoms of vulvar LS.
Other women are asymptomatic; in these patients, LS is detected by careful inspection of the vulva for the characteristic thin, white, wrinkled skin, and changes in vulvar architecture. For example, there may be loss of portions or all of the labia minora, and the clitoris may become buried under the fused prepuce. Although uncommon, active disease may be asymptomatic.
Classic vulvar LS is expressed as white, atrophic papules that may coalesce into plaques, and follicular plugging may be observed in early lesions. LS can also be hemorrhagic, purpuric, hyperkeratotic, bullous, eroded, or ulcerated. The lesions most frequently affect the labia minora and/or labia majora, although the whitening may extend over the perineum and around the anus in a keyhole fashion. Extension onto the genitocrural folds or buttocks also may occur. Fissuring is frequently seen at the posterior fourchette, perianally, in the interlabial folds, or around the clitoris. The introitus may have a yellow, waxy appearance. Fordyce spots (small raised papules along the inner aspect of the labia minora, which represent normal sebaceous glands) disappear.
Scratching may result in excoriations and secondary mild lichenification (thickening of the epidermis with exaggeration of normal skin lines), often associated with edema of the labia minora and the prepuce.
The vulvar architecture remains intact early in the course of the disease. As the disease progresses, the distinction between the labia majora and minora is lost, and the clitoris becomes buried under the fused prepuce. Shrinkage of the introitus and perineum causes dyspareunia and more fissuring upon intercourse or insertion of a speculum. At the end stages of LS, the vulva is pallid and featureless due to midline fusion, which leaves only a posterior pinhole orifice.
The diagnosis of vulvar LS is based upon the presence of characteristic clinical manifestations, ideally with histologic confirmation.
Evidence‐based guidelines from the European Academy of Dermatology and Venereology state that not all cases of adult‐onset vulvar LS require a confirmatory biopsy. However, a biopsy may be helpful to confirm the diagnosis or to reevaluate the diagnosis if initial treatment fails or if malignancy is suspected.
An association between LS and squamous cell cancer of the vulva (SCCV) has long been recognized and thought to be the result of chronic inflammation and scarring. Much of the available evidence of the relationship between LS and SCCV is based on historical studies and retrospective case series. Risk has never been defined in terms of treated versus non‐treated or unrecognized disease, or to the length of time the disease has been present. A 4.5% frequency of SCCV arising in LS has been estimated, with an average duration of antecedent LS of 10 years. This frequency is probably an overestimate. Earlier detection, the introduction of potent topical corticosteroids, the more liberal use of outpatient biopsy, excision of abnormally thickened skin resistant to medical treatment, and an increased appreciation of the nature and management of the condition hopefully will contribute to a reduction in the risk of vulvar cancer in women diagnosed with LS today. Those women who are not treated or have irregular treatment for their LS seem to be at a greater risk of developing cancer, although the figures are too small to be statistically significant.
Therefore, we recommend treatment of all women with vulvar LS, including those who are asymptomatic, to try to prevent progression of the disease. The goals of therapy should be resolution of the symptoms (pruritus and pain) and signs of disease, including hyperkeratosis, fissuring, and ecchymoses [20]. Atrophy and depigmentation may sometimes improve with therapy; however, scarring, if present, will remain. Clinical photography may assist in monitoring of the disease and can be helpful when showing patients were to apply topical therapy.
We recommend initial treatment of vulvar lichen sclerosus with a superpotent topical corticosteroid ointment. We typically administer clobetasol propionate 0.05% ointment or halobetasol propionate 0.05% ointment daily at night for 6–12 weeks, followed by maintenance therapy two to three times per week if symptoms improve. Thickened hypertrophic plaques may respond best to intralesional corticosteroid therapy.
In patients with persistent symptoms, we suggest a careful evaluation for causes of treatment failure (Figure 13).
Figure 13.
Vulvar lichen sclerosus.
11.2.3. Vulvar intraepithelial neoplasia (VIN)
Traditionally, squamous VIN was classified into three grades, analogous to the three‐grade cervical intraepithelial neoplasia classification. In 2004, ISSVD replaced the previous three‐grade classification system with a single‐grade system, in which only high‐grade disease is classified as VIN [21]. In that system, VIN is subdivided into
Usual type VIN (including warty, basaloid, and mixed VIN)
Commonly, it is associated with carcinogenic genotypes of HPV and other HPV persistence risk factors, such as cigarette smoking and immunocompromised status.
Differentiated VIN: It is associated with lichen sclerosus and a squamous cell carcinoma of the vulva than usual type VIN. Furthermore, it has a higher recurrence rate [22] and decreased disease‐specific survival from invasive squamous cell carcinoma [23].
Based on the 2015 ISSVD terminology of vulvar squamous intraepithelial lesions, usual type of VIN is now classified as vulvar HSIL, and differentiated VIN remains the same. Flat lesions associated with basal atypia and koilocytic changes (formerly termed VIN 1) are considered LSIL (condyloma or HPV effect) in the current 2015 ISSVD classification system.
Basaloid/warty SCCs develop from classic or usual VIN (uVIN) which occurs more commonly, but not solely, in relatively young women between the ages of 40 and 50 years and is associated with high‐risk HPV infection, most often HPV 16 and less commonly HPV 18 or HPV 33. In addition, uVIN is usually multifocal, multicentric, and therefore associated with other lower anogenital intraepithelial neoplasia including cervical, vaginal, and anal.
There has been an increase in the incidence of uVIN, and in some countries, the incidence has doubled in the past 10 years.
11.2.3.1.1. Gross findings
Low‐grade uVIN presents usually as single or multiple pale‐whitish areas, whereas high‐grade uVIN presents as multifocal raised plaques or papules that tend to coalesce. A small percentage of the lesions (10%) may be hyperpigmented. There is a high frequency of mutlifocality in patients presenting with multiple lesions within the lower female anogenital tract [24].
Evidence exists that VIN III may progress to invasive vulvar carcinoma. However, the available literature suggests that the progression rate to invasive vulvar carcinoma is low (Figure 14).
Figure 14.
VIN: hyperpigmented multifocal raised plaques.
11.2.3.2. Differentiated or simplex‐type vulvar intraepithelial neoplasia
Although dVIN can occur in young patients, this type of VIN is usually found in postmenopausal women and tends to be unifocal and unicentric. Frequently, dVIN develops in women with chronic dermatological diseases such as squamous cell hyperplasia, lichen sclerosus (LS), and lichen simplex chronicus. In addition, mutation of the p53 gene seems to be an early event in the development of dVIN [25] with studies showing identical p53 mutations in LS and adjacent SCC.
11.2.3.2.1. Gross findings
dVIN is found in patients with chronic skin conditions related to LS, squamous cell hyperplasia, and lichen simplex chronicus. However, clinical presentation is nonspecific with patients often being asymptomatic. They may present with focal discoloration, ill‐defined white plaques as well as red hyperkeratotic lesions. Pruritus and pain are the most frequent symptoms.
dVIN has a higher risk of progression to invasive SCC than uVIN, and time of progression to SCC is significantly shorter in dVIN cases when compared with uVIN.
\n',keywords:"colposcopy, vulvar, infections, trauma, Liquen esclerosus, HPV, VIN",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/56814.pdf",chapterXML:"https://mts.intechopen.com/source/xml/56814.xml",downloadPdfUrl:"/chapter/pdf-download/56814",previewPdfUrl:"/chapter/pdf-preview/56814",totalDownloads:1977,totalViews:850,totalCrossrefCites:1,totalDimensionsCites:1,totalAltmetricsMentions:0,introChapter:null,impactScore:1,impactScorePercentile:64,impactScoreQuartile:3,hasAltmetrics:0,dateSubmitted:"September 12th 2016",dateReviewed:"March 24th 2017",datePrePublished:null,datePublished:"September 20th 2017",dateFinished:"August 31st 2017",readingETA:"0",abstract:"Due to the normal histology of this area and the multifocal nature of vulvar intraepithelial disease, vulvoscopy is more difficult and less objective than the cervix examination. Basis of vulvar colposcopy as well as benign vulvar skin disorders that are usually found in a routine gynecology examination will be reviewed.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/56814",risUrl:"/chapter/ris/56814",book:{id:"5728",slug:"colposcopy-and-cervical-pathology"},signatures:"Marta García-Yuste González, Ana Maria Muñoz Ledesma, Mayte Navarro Monge and José Schneider Fontán",authors:[{id:"195677",title:"Prof.",name:"Marta",middleName:null,surname:"García -Yuste",fullName:"Marta García -Yuste",slug:"marta-garcia-yuste",email:"martagyuste@hotmail.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"University of Valladolid",institutionURL:null,country:{name:"Spain"}}},{id:"195987",title:"Prof.",name:"Ana",middleName:null,surname:"Muñoz Ledesma",fullName:"Ana Muñoz Ledesma",slug:"ana-munoz-ledesma",email:"amzledesma@yahoo.es",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"University of Valladolid",institutionURL:null,country:{name:"Spain"}}},{id:"195988",title:"Dr.",name:"Mayte",middleName:null,surname:"Navarro Monge",fullName:"Mayte Navarro Monge",slug:"mayte-navarro-monge",email:"maitechu@yahoo.es",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"University of Valladolid",institutionURL:null,country:{name:"Spain"}}}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Tissue basis of colposcopy of the vulva",level:"1"},{id:"sec_3",title:"3. Technique of vulvoscopy",level:"1"},{id:"sec_3_2",title:"3.1. Inspection",level:"2"},{id:"sec_4_2",title:"3.2. Application of acetic acid",level:"2"},{id:"sec_5_2",title:"3.3. Collins test",level:"2"},{id:"sec_6_2",title:"3.4. Biopsy",level:"2"},{id:"sec_8",title:"4. Physiological hyperplasia (vestibular papillomatosis)",level:"1"},{id:"sec_9",title:"5. Vulvar infections",level:"1"},{id:"sec_10",title:"6. Bacterial infections",level:"1"},{id:"sec_10_2",title:"6.1. Folliculitis",level:"2"},{id:"sec_11_2",title:"6.2. Cellulitis",level:"2"},{id:"sec_12_2",title:"6.3. Necrotizing fasciitis",level:"2"},{id:"sec_13_2",title:"6.4. Hidradenitis suppurativa",level:"2"},{id:"sec_15",title:"7. Bartholin’s abscess",level:"1"},{id:"sec_15_2",title:"7.1. Syphilis",level:"2"},{id:"sec_16_2",title:"7.2. Chancroid",level:"2"},{id:"sec_17_2",title:"7.3. Lymphogranuloma venereum",level:"2"},{id:"sec_19",title:"8. Fungus infection",level:"1"},{id:"sec_19_2",title:"8.1. Candidiasis",level:"2"},{id:"sec_20_2",title:"8.2. Dermatophytosis (Tinea infections)",level:"2"},{id:"sec_22",title:"9. Parasites infection",level:"1"},{id:"sec_22_2",title:"9.1. Scabies",level:"2"},{id:"sec_23_2",title:"9.2. Pediculosis pubis",level:"2"},{id:"sec_25",title:"10. Virus infections",level:"1"},{id:"sec_25_2",title:"10.1. Molluscum contagiosum",level:"2"},{id:"sec_26_2",title:"10.2. Herpes virus",level:"2"},{id:"sec_28",title:"11. Human papilloma virus (HPV) infection",level:"1"},{id:"sec_28_2",title:"11.1. Clinical HPV infection",level:"2"},{id:"sec_28_3",title:"11.1.1. Condyloma acuminata",level:"3"},{id:"sec_30_2",title:"11.2. Subclinical infections",level:"2"},{id:"sec_30_3",title:"11.2.1. Vulvar trauma",level:"3"},{id:"sec_31_3",title:"11.2.2. Liquen esclerosus (LS)",level:"3"},{id:"sec_32_3",title:"11.2.3. Vulvar intraepithelial neoplasia (VIN)",level:"3"},{id:"sec_32_4",title:"11.2.3.1. Usual vulvar intraepithelial neoplasia (classic VIN, uVIN)",level:"4"},{id:"sec_32_5",title:"11.2.3.1.1. Gross findings",level:"5"},{id:"sec_34_4",title:"11.2.3.2. Differentiated or simplex‐type vulvar intraepithelial neoplasia",level:"4"},{id:"sec_34_5",title:"11.2.3.2.1. Gross findings",level:"5"}],chapterReferences:[{id:"B1",body:'Powell JL. Biographic sketch: Powell’s pearls: Hans Peter Hinselmann, MD (1884-1959). Obstetrical & Gynecological Survey. 2004;59:693-695'},{id:"B2",body:'Maddox P, Szarewski A, Dyson J, et al. Cytokeratin expression and acetowhite change in cervical epithelium. Journal of Clinical Pathology. 1994;47:15-17'},{id:"B3",body:'Burke L, Antonioli DA, Ducatman BS. Colposcopy: Text and Atlas. Norwalk, CT: Appleton and Lange; 1991'},{id:"B4",body:'Collins CG, Hansen LH, Theriot E. A clinical stain for use in selecting biopsy sites in patients with vulvar disease. Obstetrics and Gynecology. 1966;28(2):158-163'},{id:"B5",body:'Micheletti L, Bogliatto F, Lynch PJ. Vulvoscopy: Review of a diagnostic approach requiring clarification. The Journal of Reproductive Medicine. 2008;53(3):179-182'},{id:"B6",body:'American College of Obstetricians and Gynecologists’ Committee on Gynecologic Practice.; American Society for Colposcopy and Cervical Pathology (ASCCP).'},{id:"B7",body:'Modesitt SC, Waters AB, Walton L, et al. Vulvar intraepithelial neoplasia. III. Occult cancer and the impact of margin status on recurrence. Obstetrics and Gynecology. 1998;92(6):262-266'},{id:"B8",body:'Rodríguez Prieto MA, Vega Gutiérrez J, Sánchez Sambucety P. Vestibullar papillae of the vulva. International Journal of Dermatology. 2004;43:143-144'},{id:"B9",body:'Beznos G, Coates V, Focchi J, Hatim AO. Biomolecular study of the correlation between papillomatosis of the vulvar. Vestibule in Adolescents and Human Papillomavirus. The Scientific World Journal. 2006;6:628-636'},{id:"B10",body:'Chan CC, Chiu HC. Images in clinical medicine. Vestibular papillomatosis. The New England Journal of Medicine. 2008:358-314'},{id:"B11",body:'Obstetrics and Gynecology 2011. Vol. 2. Usandizaga, De la Fuente'},{id:"B12",body:'Sánchez M,, Torres JV. Hidrosadenitis supurativa vulvar,Vulvar suppurative hidrosadenitis. Progresos de Obstetricia y Ginecología. 2003;46:185-189. DOI: 10.1016/S0304‐5013(03)75880‐4'},{id:"B13",body:'Welch JM, Nayagam M, Parry G, Das R, Campbell M, Whatley J, et al. What is vestibular papillomatosis? A study of its prevalence, aetiology and natural history. British Journal of Obstetrics and Gynaecology. 1993;100:939-942'},{id:"B14",body:'Patel H, Wagner M, Singhal P, Kothari S. Systematic review of the incidence and prevalence of genital warts.. Infectious Diseases. 2013;13:39'},{id:"B15",body:'King EM, Gilson R, Beddows S, Soldan K, Panwar K, Young C, Prah P, Jit M, Edmunds WJ, Sonnenberg P. Human papillomavirus DNA in men who have sex with men: type‐specific prevalence, risk factors and implications for vaccination strategies. British Journal of Cancer. 2015;112(9):1585-1593'},{id:"B16",body:'Hoy T, Singhal PK, Willey VJ, Insinga. Assessing incidence and economic burden of genital warts with data from a US commercially insured population. Current Medical Research and Opinion. 2009;25(10):2343-2351'},{id:"B17",body:'Weiss DA, Yang G, Myers JB, Breyer BN. Condyloma overgrowth caused by immune reconstitution inflammatory syndrome. Urology. 2009;74(5):1013-1014'},{id:"B18",body:'Workowski KA, Bolan GA, Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2015. MMWR Recommendations and Reports. 2015;64(RR‐03):1'},{id:"B19",body:'von Krogh G, Lacey CJ, Gross G, Barrasso R, Schneider A. European course on HPV associated pathology: Guidelines for primary care physicians for the diagnosis and management of anogenital warts. Sexually Transmitted Infections. 2000;76(3):162'},{id:"B20",body:'Neill SM, Lewis FM, Tatnall FM, Cox NH, British Association of Dermatologists. British Association of Dermatologists’ guidelines for the management of lichen sclerosus 2011. British Journal of Dermatology. 2010;163(4):672'},{id:"B21",body:'Committee on Gynecologic Practice American Society for Colposcopy and Cervical Pathology. October 2016;675:'},{id:"B22",body:'Eva LJ, Ganesan R, Chan KK, Honest H, Malik S, Luesley DM. Vulval squamous cell carcinoma occurring on a background of differentiated vulval intraepithelial neoplasia is more likely to recur: A review of 154 cases. The Journal of Reproductive Medicine. 2008;53:397-401'},{id:"B23",body:'van de Nieuwenhof HP, van Kempen LC, de Hullu JA, Bekkers RL, Bulten J, Melchers WJ, et al. The etiologic role of HPV in vulvar squamous cell carcinoma fine tuned. Cancer Epidemiology Biomarkers & Prevention. 2009;18:2061-2067'},{id:"B24",body:'Yang B, Hart WR. Vulvar intraepithelial neoplasia of the simplex (differentiated) type: A clinicopathologic study including analysis of HPV and p53 expression. The American Journal of Surgical Pathology. 2000;24:429-441'},{id:"B25",body:'Pinto AP, Miron A, Yassin Y, et al. Differentiated vulvar intraepithelial neoplasia contains Tp53 mutations and is genetically linked to vulvar squamous cell carcinoma. Modern Pathology. 2010;23:404-412'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Marta García-Yuste González",address:"martagyuste@hotmail.com",affiliation:'
Faculty of Medicine, Valladolid, Spain
'},{corresp:null,contributorFullName:"Ana Maria Muñoz Ledesma",address:null,affiliation:'
Our society is presented with grand challenges. We have to deal with many issues at the same time, such as climate change, the energy transition, the transition to a circular economy, empowered citizens, the increasing role of digitization, increasing attention to the living environment and nature, etc. This means that projects, which can be seen as interventions in our society, can no longer be separated from their environment. Current project management, however, still follows a hedging approach that is strongly based on the classical step-wise development of a predefined output, where the environment is seen as a threat that must be mitigated. In order to be able to respond to the increasing complexity of the project environment, there is an emerging demand for a more open and interactive approach to project management. We refer to this approach as a flexing approach. While a flexing approach may emphasize the ability of projects to move along with and shape their environment, this also increases the interdependencies between the project and its environment, thereby increasing complexity, leading to less control of the project and potentially causing projects to drift. Therefore, it is necessary to find a form of project management that is open and interactive without losing control. The theory and practice of process management offer valuable insights for this. On the basis of insights from recent project and process management literature, this chapter describes how strategies and instruments of process management can be combined with project management tools and techniques to come to a more open form of management without losing manageability.
2. From hedging to flexing in project management
2.1 What is meant by “project” and “project management”?
Literature has numerous definitions of the term “project.” One of the most used definitions was developed by Turner and Müller [1], who define a project as a temporary endeavor in which human, material, and financial resources are organized in a novel way, to undertake a unique scope of work, of given specification, within constraints of cost and time, so as to achieve beneficial change defined by quantitative and qualitative objectives. Following this definition, project management can be seen as the organizational activities, to be carried out by a plurality of specialized persons or groups, in a temporary joint venture that aims to deliver a clearly specified result within a limited period of time, within certain conditions and with finite resources. In short, project management concerns the application of knowledge, skills, tools, and techniques to ensure that project activities meet project requirements [2].
2.2 Limitations of classic project management
Classic project management is strongly focused on manageability and control. It is based on a causal rational paradigm [3, 4], where the process of managing a project is translated in a sequential and linear phasing of activities that should lead to a predefined result. This is further expressed in scope, cost, and time management using dedicated project management tools and techniques, suggesting that the appropriate use of these instruments leads to the intended result. In this paradigm, the project is regarded as a closed system with a clear boundary to its environment. This system is not isolated—there is interaction between the system and its environment—but changes in that environment may have a negative effect on project progress and are considered a potential threat that must be mitigated. Projects are therefore supposed to conduct risk analyses and develop contingency plans to cope with risk. In general, classic project management is based on advanced predictions that must be achieved via a strictly defined path through the correct and effective use of project management tools and techniques. These tools and techniques take the form of methods, rules, step-by-step procedures, frameworks, and models. A search on Google quickly reveals the multitude of project management tools and techniques and a multitude of handbooks that describe these [2, 5, 6]. Organizations such as the International Project Management Association (IPMA) and the Project Management Institute (PMI) even offer dedicated courses to learn these tools and techniques and to certify project managers.
However, due to this closed system perspective, potential opportunities may be missed and the defensive attitude may lead to problems in delivering projects. This limits the contribution that projects can (and should) make to the major societal challenges we are facing today and the potential use of opportunities as tool for adaptation. In addition, society is becoming increasingly engaged, and a sectoral project-oriented process without the engagement of its environment is no longer accepted. Or as Van Buuren et al. [7] argued, the main characteristic and focus of (classic) project management is its main disadvantage: it tends to focus primarily on the realization of one single project ambition, suffers from a singular logic, and is limited in terms of scope, budget, and time. An answer may be a more open system approach in which the boundary of the system becomes permeable and stakeholders are included as co-actors, especially in more dynamic environments with a relatively high degree of uncertainty. A shift in focus of project management from purely instrumental to more process-oriented.
2.3 From hedging to flexing
Classic project management, based on a hedging strategy, offers hardly any room for adjustments to the project scope, planning, or budget, to respond to changes in the environment. In general, hedging is less satisfactory in dynamic environments when complexity in and around the project is relatively high. In these cases, a process-oriented approach, or flexing, is more appropriate. Flexing is often characterized by a broader scope (integration of challenges), a flexible planning on various timescales (short, medium, and long term), interim monitoring, a partly flexible budget to which several parties contribute (co-financing), and involvement of stakeholders through open dialog and a co-creative approach. Determining the right mix, i.e., a balance between hedging and flexing (which may even change over time), is the key challenge in modern project management. This mix is determined by both the context of the project and the capabilities of the project organization. By “context” we mean the unique conditions in which the project is being managed [8], including the organization’s internal context (e.g., other projects, departments, and organizational strategy), and external context (e.g., stakeholders, adjacent environment). Table 1 shows main characteristics of classic project management and a process-oriented approach [9].
(Classic) project management
Process management
Main focus
A well-thought-out solution to a problem
Organic development of a solution to a problem or problems through involvement of stakeholders and their interests
Dealing with dynamics
Through decisiveness and control
Through resilience, responsiveness and being open to other options
Changing circumstances must not affect the course of action
Changing circumstances are windows of opportunity.
The project has the ability to deal with change (adaptive capacity)
Closed system focus
Open system focus.
Interaction with the project environment for enrichment (opportunities, integration of challenges, engagement)
Context
A stable, predictable environment
An unstable, dynamic environment
Table 1.
Main characteristics of (classic) project management and process management (derived from [9]).
In the next sections, we will first look at the context of a project from a complexity perspective. Higher degrees of complexity of a project and/or its environment require the project to deal with higher levels of uncertainty, which requires more flexibility of the project. Then we will discuss strategies to open project boundaries and to increase the ability of a project to reach out to its environment through stakeholder engagement, active opportunity seeking, and inclusive planning. Subsequently, we will discuss the ability of the project organization itself to proactively deal with uncertainty. In the final section, we will bring it all together as related building blocks for next-generation project management.
3. Projects and complexity
Complexity is an often-used concept in project development and management. In our daily use, it often refers to the perspective of the project participants on the difficulty of a project. From a more fundamental perspective, complexity revolves around actors or elements in or close to a project that interact with each other in a reciprocal way. For example, nowadays, the project environment in both project development and implementation requires intensive interaction, which may lead to a multitude of interdependent relationships of the project with its environment.
Not all projects are necessarily complex. Some projects can be classified as simple or complicated. The degree of complexity—i.e., a simple, complicated, or complex project—has implications for project management; or at least, it should have. Higher degrees of complexity often imply more uncertainty, more vulnerability for change, and need a management style that can deal with this. In general, simple or complicated projects can be managed on the basis of a hedging project management approach, whereas complex projects need more flexibility and a more flexing project management approach.
On the basis of a recent literature review of international peer-reviewed journals on project complexity, four forms of complexity can be distilled: technical or structural complexity, organizational complexity, contextual complexity, and institutional complexity [10]. Projects may have to deal with any form of complexity. Technical or structural complexity relates to the tasks and substantive aspects of a project. This not only includes the diversity and number of tasks or aspects within a project, but also the interdependencies between tasks or technologies. Organizational complexity relates to the organizational structure of the project or its parent organization. A complex organizational structure is one that consists of several interdependent parts. Institutional complexity is the result of different institutional logics of the actors involved in a project. Institutional logics influence personal definitions and working methods, which are partly shaped by the cultural and political background of the actors. For this chapter, especially the fourth identified type of complexity, the concept of contextual complexity, is relevant. Contextual complexity is described in literature as the complexity resulting from environmental influences. The literature review of Busscher et al. [10] revealed several indicators of contextual complexity, which can be used to assess the degree of complexity of a project in a specific context. The following indicators were found in the studied literature: the amount of project stakeholders, the level of sociopolitical interests or influence in project, the degree of support (from stakeholders) for the project, the internal (intra organizational) support for the project, the degree of competition in the market, geographical differences in regulations, the level of influence of contextual developments on the project, and the amount and intensity of social discussions.
As mentioned above, a higher degree of contextual complexity needs more flexibility of the project—or a more flexing style of project management. However, the need for flexibility does not (always) match the possibilities to be flexible in every phase of the project life cycle [11]. For instance, the need for flexibility may be high in the planning phase and the beginning of the execution phase when the design is elaborated and stakeholders are confronted with the concrete effects of the intervention. As the design evolves, the possibilities for flexibility will decrease and will be lower in the end of the planning phase and low in the execution phase and termination phase. Typically, in project management, a change of phase comes with an intermediate decision, which fixes the boundary conditions for the next phase and by doing so reduces the opportunities for flexibility.
4. Strategies, tools, and techniques to deal with contextual complexity
4.1 Stakeholder management and opportunity management
Already in the 1980s of the last century, Cleland (1986) introduced stakeholder thinking into project management. Since then, the importance of stakeholder management in project management has increased, i.e., the process of adapting the specifications, plans, and approaches to the different concerns and expectations of the various stakeholders [2]. A stakeholder can be defined as a group or individual that has an interest in the success or failure of a project [12]. Stakeholder management is the process of managing the expectations of anyone who has an interest in a project or will be affected by its deliverables or outputs. Stakeholder management typically has been used as an iterative process of identifying and analyzing stakeholders from a project perspective, defining strategies and accompanying measures, implementing the measures, and evaluating the effectiveness (plan-do-check-act). In this approach, the stakeholders are considered manageable to meet project goals [13]. Together with the development of stakeholder management also opportunity management gained increasing attention. Opportunity management can be seen as the inverse of risk management, in the sense that risk management seeks to proactively minimize the probability and/or negative effect of a potential event on a project and opportunity management, in turn, seeks to maximize opportunities that can bring value to a project by connecting project challenges to stakeholder challenges [14]. From a project management perspective, an opportunity is an uncertainty that potentially adds more value to the project than the potential loss of value it may bring along [15]. This interpretation of opportunity management is based on the Mutual Gains Approach as developed at Harvard University in the beginning of this century [16, 17]. Being able to seize opportunities increases the flexibility of the project, since the extra value of an opportunity may be used to, for example, extend the scope of the project or compensate for potential time or cost overruns.
4.2 Co-development
This leaves the question: can one really manage stakeholders and the project environment? As mentioned above, society becomes more emancipated. People take responsibility to design their own environment, and citizens’ initiatives are becoming more and more common [18]. The power of interest groups, NGOs, and individual stakeholders is increasing. These developments imply that projects can no longer act autonomously and instead have to work together with stakeholders. Stakeholder and opportunity management thus have to shift to an orientation focused on co-development. In contrast to “management of stakeholders,” a “management for stakeholders” approach embraces all the stakeholders and tries to reach win-win situations [19]. In line with this approach, participation through co-development is broadly discussed in planning and management literature in the last decades [20, 21, 22, 23, 24, 25].
Co-development can be defined as the joint development and improvement of policies and services at an equal level through constructive dialog [26]. Dialog means interactivity, engagement, and a propensity to act on both sides. It is about empathic understanding of both sides and a communication of equals. The intensity of joint activities can differ (see, for example, the classic ladder of participation by Arnstein, 1966), but communication and information exchange are always the basis for any stakeholder involvement. Attuning and adjusting mutual activities can be added on top of communication and information exchange so as to achieve results more efficiently, i.e., mutual coordination. When, in addition to the abovementioned activities, also resources are exchanged, one may speak of cooperation. Collaboration is considered the ultimate form of cooperation, where information, activities, resources, and responsibilities are jointly planned, implemented, and evaluated to achieve a common goal [27]. In all these definitions, joint development in equity, interaction, and dialog influence on agenda setting, high involvement and common goals are main characteristics of co-development.
4.3 Engaging stakeholders and issue management
Co-development in a project environment means that the project engages the stakeholders in a collaborative problem-solving process [28]. The project organization respects and uses the expertise of the stakeholders and is open and willing to share all information necessary for a joint project design. The design is based on problem-specific interaction involving the interests of all relevant stakeholders. The decision-making is based on the weighing of interests in what Aaltonen & Sivonen [29] describe as an adaptation strategy. Figure 1 shows different corresponding strategies as mentioned in literature the axis from (classic) project management to process management.
Figure 1.
Strategies for project and process management.
Strategic stakeholder Involvement (SSI) is a practical tool to engage stakeholders in co-development [30]. This approach combines traditional stakeholder management, designed to minimize risks caused by parties with different interests, with seizing opportunities through issue management. Issue management entails a process of continuously scanning the environment for new issues, which are developments or events that might happen and force stakeholders to take position. Issues come and go and change over time. Central to issue management is the identification of issues that may influence the project or may be influenced by the project and address these in interaction with the stakeholders from a win-win perspective.
4.4 Co-creation and social design
The descriptions above are based on a so-called inside-out perspective, which looks at the environment from within the project. At the same time, the project can also be seen as an instrument that may contribute to solving broader social issues. This perspective works from the outside-in and assumes the project goal and task to be only one of the goals and tasks that have to be tackled in interaction with and between stakeholders, thus opening the box [13].
Social design is a design methodology to tackle complex issues, placing the combined social issues as the priority. The basic idea is to break down the walls between disciplines and enable truly interdisciplinary work to take place. The classic approach of project management starts with a (project) problem and organizes the most efficient path to come to a predefined output or outcome, which solves that problem. Social design is based on the process and principles of design thinking developed by the British Design Counsel (www.designcounsil.org.uk), the “Double Diamond” or “4D” model. In this approach, the design process starts with a joint problem definition involving all relevant problems of the project and its context and their stakeholders. The idea is that actors collectively scan a relevant context around the project searching for problems and issues. Based on a joint problem definition, information is gathered and possible combinations are developed in a co-creative process. In contrast to the traditional project management life cycle, this process is not linear from problem to solution, but interactively dynamic via diverging and converging stages [20, 31]. Figure 2 shows the typical steps of a social design process.
Figure 2.
Process steps of social design (source: British Design Counsel).
Social design may lead to more integrated solutions and a higher degree of acceptance. However, to keep the process manageable, it is necessary to add some hedging elements to the process, for example, by setting milestones, by setting clear and smart boundaries, and by transparently communicating about the boundaries of the decision-making process.
5. Building project flexibility
The project context is essential for the successful management of a project [32]. As mentioned above, project organizations need to be responsive and open up to their context and engage stakeholders to enable project success. This requires considerable flexibility of the project organization, as it includes giving room for co-development and co-creation and at the same time keeping the project manageable [8]. Olsson [33] defines project flexibility as the capability to adjust the project to prospective consequences of uncertain circumstances within the context of the project. Adopting a flexible approach improves not only the project results, but also the evaluation of the project management itself.
The extended Pentagon model of Rolstadås et al. [34] offers a model to connect the project management process to the external context through so-called formal qualities, such as structure and technologies, and informal qualities, such as culture, social relations and networks, and interaction (see Figure 3).
Figure 3.
The extended pentagon model (source: [34]).
The distinction between formal and informal qualities may be viewed as hedging versus flexing, controlling versus emerging, or prescriptive versus adaptive. In this model, flexibility is created through the interaction between formal and informal qualities of project organizations. For example, rules may formally be more loosely defined to allow informal qualities to be revealed. Building on this, Sohi et al. [35] delivered a list of flexibility enablers regarding both formal and informal qualities of project organizations as shown in Table 2.
Extended pentagon model
Flexibility enablers
Collective learning
Formal qualities
Structure
Broad task definition
Institutional design
Functional-based contracts
Multilevel integration
Standardized processes
Stable teams
Self-steering of the project team
Self-assigning of individuals to tasks
Late locking
Short feedback loops
Continuous locking (iterative)
Iterative planning
Iterative delivery
Technologies
Contingency planning
Information management
Visualized project planning and progress
Shared interface management
Joint project office
Informal qualities
Culture
Seizing opportunities and coping with threats
Diversity
Possible alternatives
Scope for change
Embrace change as much as needed
Leadership
Team priority over individual priority
Capabilities of individuals
Consensus among team members
Interaction
Open information exchange among different groups
Rules for dialog
Social relations and networks
Trust among involved parties
Trust and open atmosphere
Network structure rather than hierarchical structure
Informal network
Team members as stakeholders
Learning platforms
Continuous learning
Table 2.
Overview of the extended pentagon model in relation to flexibility enablers and collective learning.
The model is dynamic and involves continuous iterative processes within the project organization and interaction with external stakeholders and contexts. The project team members receive feedback from stakeholders or the context. This feedback is interpreted both individually and collectively. Positive feedback reinforces successful practices, whereas negative feedback will lead to an attempt to alter existing practices. This multilevel process of collective learning is a process of adaptation consisting of changes in common understanding, mutual agreement, and collective action. The ability to build new knowledge, relationships, and practices in response to complex environmental challenges links (collective) learning to flexibility. In fact, collective learning may even be considered a proxy for flexibility. De Groot et al. [36] describe in their article typical identifiers of collective learning in project-oriented organizations as summarized in Table 2.
The enablers and indicators shown in Table 2 resemble the aforementioned characteristics of process management (see Table 1). In general, adaptive project management or flexibility requires a more open approach both within the system of a project organization and through interaction with the project context.
While this might be seen to decrease the control of the project, an open approach does not necessarily lead to a loss of control, but to a different form of control. Project organizations still need a solid structure with clear roles and responsibilities. However, to enable flexibility, project management may lower barriers between disciplines and promote horizontal and vertical integration through cross-discipline meeting structures and decision-making processes. Project organizations still need technologies, such as skills, tools, and techniques to manage the project. However, the corresponding tools and infrastructure may allow for more explicit anticipation of contingencies through, for example, scenario analyses or systems that enable easy access to information throughout the project organization. Finally, there needs to be a culture that enables flexibility. Team members may have to get used to a (partially) new way of working. They may be encouraged to look for creative and integral solutions and to view changes as opportunities. In this, important is the organization of interaction through social relations and networks based on open information exchange leading to trust and effective collaboration within the project organization and with the project’s stakeholders.
6. Balancing hedging and flexing for inclusive project management
Classic project management is based on a closed system approach, where the context is typically seen as a threat for the efficient delivering of the project output or outcome, which has to be mitigated through risk management. We referred to this as a hedging approach. However, the increasingly dynamic and engaged society requires an open (inclusive) approach, where challenges are integrated and stakeholders are involved in the development of the project. In general, opening project boundaries may lead to higher contextual complexity. A higher degree of contextual complexity needs more flexibility of the project or a more flexing style of project management. This leads to an important paradox in current project management. To efficiently manage their projects, project managers need (or are forced) to organize interaction with the project context or their community of interest, while involving more stakeholders or integrating more challenges in the project will lead to more (contextual) complexity and more uncertainty. Consequently, an important task for the project manager is to find a balanced mix between hedging and flexing tools and techniques. Adding to the challenge is the fact that this mix may change during the project phases, because the need for flexing and the possibilities to implement flexing tools and techniques differ per project stage. In practice, in the planning phase, the need for flexibility is relatively high because the elaboration of the project design confronts stakeholders with the concrete effects of interventions, whereas the possibilities to flex are relatively high in this phase because there are still relatively few agreements, little expenses made, and hardly any concrete results realized. As a project progresses, it becomes increasingly difficult to alter the desired project output due to, for example, ongoing agreements between stakeholders and realized project parts limiting the possibilities for other solutions. However, implementing flexing tools and techniques to engage stakeholders remains also in the latter phases important as (most) projects are realized in a continuously changing environment.
Figure 4 gives an overview of the building blocks that become increasingly important in modern, inclusive project management; arranged in such a way that from the left to the right, tools and techniques offer more flexibility.
Figure 4.
Building blocks for inclusive project management.
7. Conclusion
This chapter has provided an array of tools and techniques that can be used to compose a balanced mix of hedging and flexing for inclusive project management. As such, it provides the building blocks that help to shift the orientation of project managers from a project-problem centrality to a focus on multiple contextual problems and challenges. We argue that project organizations should always strive for project flexibility. Projects, being simple, complicated, or complex, are always potentially confronted with unexpected events. Being flexible may then be the answer to deal with these uncertainties. As discussed above, being able to create diversity and learning are key to increase project flexibility.
Projects are temporary endeavors, which means that they have a beginning and an end. As discussed, in dynamic and engaged contexts, a more open approach of project management may be necessary, which potentially leads to more diversity. However, to come to an end, this diversity has to be converged and funneled by intermediate decision-making or hedging. The real art of modern, inclusive project management is defining a balanced mix of hedging and flexing in every phase of the project.
\n',keywords:"project management, hedging, flexing, stakeholder participation",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/80714.pdf",chapterXML:"https://mts.intechopen.com/source/xml/80714.xml",downloadPdfUrl:"/chapter/pdf-download/80714",previewPdfUrl:"/chapter/pdf-preview/80714",totalDownloads:7,totalViews:0,totalCrossrefCites:0,dateSubmitted:"January 15th 2022",dateReviewed:"February 1st 2022",datePrePublished:"May 12th 2022",datePublished:null,dateFinished:"March 3rd 2022",readingETA:"0",abstract:"Current project management often emphasizes hedging through a strictly phased and funneled development of the project scope. However, an increasingly engaged project environment and rise in the complexity of societal challenges cause an emerging demand for more open and interactive ways of managing projects. This requires projects to adopt an integrated management approach that focuses on flexing, which emphasizes the ability of a project to adapt to and co-create with the environment. Overemphasizing flexing, however, may undermine the controlled nature of project management. Therefore, it is necessary to find a form of project management that is both open and interactive without losing control. On the basis of specific project contexts and characteristics, this chapter presents criteria and tools for balancing hedging and flexing for inclusive project management.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/80714",risUrl:"/chapter/ris/80714",signatures:"Wim Leendertse, Bert de Groot and Tim Busscher",book:{id:"11260",type:"book",title:"Project Management - New Trends and Applications",subtitle:null,fullTitle:"Project Management - New Trends and Applications",slug:null,publishedDate:null,bookSignature:"Prof. Marinela Mircea and Dr. Tien M. 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Strategies, tools, and techniques to deal with contextual complexity",level:"1"},{id:"sec_7_2",title:"4.1 Stakeholder management and opportunity management",level:"2"},{id:"sec_8_2",title:"4.2 Co-development",level:"2"},{id:"sec_9_2",title:"4.3 Engaging stakeholders and issue management",level:"2"},{id:"sec_10_2",title:"4.4 Co-creation and social design",level:"2"},{id:"sec_12",title:"5. Building project flexibility",level:"1"},{id:"sec_13",title:"6. Balancing hedging and flexing for inclusive project management",level:"1"},{id:"sec_14",title:"7. Conclusion",level:"1"}],chapterReferences:[{id:"B1",body:'Turner R, Müller R. On the nature of the project as a temporary organisation. International Journal of Project Management. 2003;21(7):1-8'},{id:"B2",body:'PMI. A Guide to the Project Management Body of Knowledge and the Standard for Project Management. 7th ed. Project Management Institute: Pennsylvania, USA; 2021'},{id:"B3",body:'Stacey R. 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\r\n\tTransforming our World: the 2030 Agenda for Sustainable Development endorsed by United Nations and 193 Member States, came into effect on Jan 1, 2016, to guide decision making and actions to the year 2030 and beyond. Central to this Agenda are 17 Goals, 169 associated targets and over 230 indicators that are reviewed annually. The vision envisaged in the implementation of the SDGs is centered on the five Ps: People, Planet, Prosperity, Peace and Partnership. This call for renewed focused efforts ensure we have a safe and healthy planet for current and future generations.
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Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. Currently, proteomics relies mainly on mass spectrometry (MS) combined with electrophoretic (1 or 2-DE-MS) and/or chromatographic techniques (LC-MS/MS). MS is an excellent tool that has gained popularity in proteomics because of its ability to gather a complex body of information such as cataloging protein expression, identifying protein modification sites, and defining protein interactions. The Proteomics topic aims to attract contributions on all aspects of MS-based proteomics that, by pushing the boundaries of MS capabilities, may address biological problems that have not been resolved yet.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/18.jpg",hasOnlineFirst:!0,hasPublishedBooks:!0,annualVolume:11414,editor:{id:"200689",title:"Prof.",name:"Paolo",middleName:null,surname:"Iadarola",slug:"paolo-iadarola",fullName:"Paolo Iadarola",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSCl8QAG/Profile_Picture_1623568118342",biography:"Paolo Iadarola graduated with a degree in Chemistry from the University of Pavia (Italy) in July 1972. He then worked as an Assistant Professor at the Faculty of Science of the same University until 1984. In 1985, Prof. Iadarola became Associate Professor at the Department of Biology and Biotechnologies of the University of Pavia and retired in October 2017. Since then, he has been working as an Adjunct Professor in the same Department at the University of Pavia. His research activity during the first years was primarily focused on the purification and structural characterization of enzymes from animal and plant sources. During this period, Prof. Iadarola familiarized himself with the conventional techniques used in column chromatography, spectrophotometry, manual Edman degradation, and electrophoresis). Since 1995, he has been working on: i) the determination in biological fluids (serum, urine, bronchoalveolar lavage, sputum) of proteolytic activities involved in the degradation processes of connective tissue matrix, and ii) on the identification of biological markers of lung diseases. In this context, he has developed and validated new methodologies (e.g., Capillary Electrophoresis coupled to Laser-Induced Fluorescence, CE-LIF) whose application enabled him to determine both the amounts of biochemical markers (Desmosines) in urine/serum of patients affected by Chronic Obstructive Pulmonary Disease (COPD) and the activity of proteolytic enzymes (Human Neutrophil Elastase, Cathepsin G, Pseudomonas aeruginosa elastase) in sputa of these patients. More recently, Prof. Iadarola was involved in developing techniques such as two-dimensional electrophoresis coupled to liquid chromatography/mass spectrometry (2DE-LC/MS) for the proteomic analysis of biological fluids aimed at the identification of potential biomarkers of different lung diseases. He is the author of about 150 publications (According to Scopus: H-Index: 23; Total citations: 1568- According to WOS: H-Index: 20; Total Citations: 1296) of peer-reviewed international journals. 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